Circulating Acylcarnitines Associated with Hypertrophic Cardiomyopathy Severity: an Exploratory Cross-Sectional Study in MYBPC3 Founder Variant Carriers.

Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease characterised by myocardial hypertrophy. HCM can cause outflow tract obstruction, sudden cardiac death and heart failure, but severity is highly variable. In this exploratory cross-sectional study, circulating acylcarnitines were assessed as potential biomarkers in 124 MYBPC3 founder variant carriers (59 with severe HCM, 26 with mild HCM and 39 phenotype-negative [G + P-]). Elastic net logistic regression identified eight acylcarnitines associated with HCM severity. C3, C4, C6-DC, C8:1, C16, C18 and C18:2 were significantly increased in severe HCM compared to G + P-, and C3, C6-DC, C8:1 and C18 in mild HCM compared to G + P-. In multivariable linear regression, C6-DC and C8:1 correlated to log-transformed maximum wall thickness (coefficient 5.01, p = 0.005 and coefficient 0.803, p = 0.007, respectively), and C6-DC to log-transformed ejection fraction (coefficient -2.50, p = 0.004). Acylcarnitines seem promising biomarkers for HCM severity, however prospective studies are required to determine their prognostic value.

BIO FOr CARE: biomarkers of hypertrophic cardiomyopathy development and progression in carriers of Dutch founder truncating MYBPC3 variants-design and status.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by truncating variants in the MYBPC3 gene. HCM is an important cause of sudden cardiac death; however, overall prognosis is good and penetrance in genotype-positive individuals is incomplete. The underlying mechanisms are poorly understood and risk stratification remains limited. AIM: To create a nationwide cohort of carriers of truncating MYBPC3 variants for identification of predictive biomarkers for HCM development and progression. METHODS: In the multicentre, observational BIO FOr CARe (Identification of BIOmarkers of hypertrophic cardiomyopathy development and progression in Dutch MYBPC3 FOunder variant CARriers) cohort, carriers of the c.2373dupG, c.2827C > T, c.2864_2865delCT and c.3776delA MYBPC3 variants are included and prospectively undergo longitudinal blood collection. Clinical data are collected from first presentation onwards. The primary outcome constitutes a composite endpoint of HCM progression (maximum wall thickness ≥ 20 mm, septal reduction therapy, heart failure occurrence, sustained ventricular arrhythmia and sudden cardiac death). RESULTS: So far, 250 subjects (median age 54.9 years (interquartile range 43.3, 66.6), 54.8% male) have been included. HCM was diagnosed in 169 subjects and dilated cardiomyopathy in 4. The primary outcome was met in 115 subjects. Blood samples were collected from 131 subjects. CONCLUSION: BIO FOr CARe is a genetically homogeneous, phenotypically heterogeneous cohort incorporating a clinical data registry and longitudinal blood collection. This provides a unique opportunity to study biomarkers for HCM development and prognosis. The established infrastructure can be extended to study other genetic variants. Other centres are invited to join our consortium.

High protein prescription in methylmalonic and propionic acidemia patients and its negative association with long-term outcome.

BACKGROUND AND OBJECTIVE: Methylmalonic acidemia (MMA) and propionic acidemia (PA) are inborn errors of metabolism. While survival of MMA and PA patients has improved in recent decades, long-term outcome is still unsatisfactory. A protein restricted diet is the mainstay for treatment. Additional amino acid mixtures (AAM) can be prescribed if natural protein is insufficient. It is unknown if dietary treatment can have an impact on outcome. DESIGN: We performed a nationwide retrospective cohort study and evaluated both longitudinal dietary treatment and clinical course of Dutch MMA and PA patients. Protein prescription was compared to the recommended daily allowances (RDA); the safe level of protein intake as provided by the World Health Organization. The association of longitudinal dietary treatment with long-term outcome was evaluated. RESULTS: The cohort included 76 patients with a median retrospective follow-up period of 15 years (min-max: 0-48 years) and a total of 1063 patient years on a protein restricted diet. Natural protein prescription exceeded the RDA in 37% (470/1287) of all prescriptions and due to AAM prescription, the total protein prescription exceeded RDA in 84% (1070/1277). Higher protein prescriptions were associated with adverse outcomes in severely affected patients. In PA early onset patients a higher natural protein prescription was associated with more frequent AMD. In MMA vitamin B12 unresponsive patients, both a higher total protein prescription and AAM protein prescription were associated with more mitochondrial complications. A higher AAM protein prescription was associated with an increased frequency of cognitive impairment in the entire. CONCLUSION: Protein intake in excess of recommendations is frequent and is associated with poor outcome.

Floristic characterization of the Los Lanches relict of the Montane Forest Las Palmas ­ Chota, Peru / Caracterización florística del relicto Los Lanches del Bosque Montano Las Palmas ­ Chota, Perú / Caracterização florística do remanescente Los Lanches da Floresta Montana Las Palmas - Chota, Peru

Montane forests are ecosystems with valuable endemic species; however, they have been degraded and reduced to forest relics, their floristic diversity is not fully known. The object of the study was the floristic characterization of the Los Lanches relict of the Las Palmas montane forest, located to the south of the Conchan district, Chota, Peru, between 2,800 and 3,000 elevation meters. 30 species distributed in 27 genera and 23 families were identified, Myrtaceae, Lauraceae, and Melastomataceae are the most representative. A mixing coefficient of 0.033 was obtained. The Simpson index of 0.89 indicates high diversity and the Shannon-Wiener index of 2.28. The horizontal distribution by diameter classes presented a trend line of an inverted "J". The Weinmannia elliptica (16.62 %), Hedysomum scabrum (10.26 %), Cyathea caracasana (8.44 %), and Nectandra lineatifolia (6.03 %) presented a value index of high importance. The vertical distribution in height classes presented the trend of inverted "j", observing that 20 % of species are found in the three strata. Hedyosmum scabrum (98.6), Cyathea caracasana (69.8), and Weinmannia elliptica (69.8) present high phytosociological values. The most important in natural regeneration are Hedyosmum scabrum (27.79 %) and Palicourea amethystina (14.77 %). The species with a high value of expanded importance Hedyosmum scabrum (19.24 %), Weinmannia elliptica (11.44 %), and Palicourea amethystina (8.02 %).

Los bosques montanos son ecosistemas con especies endémicas valiosas; sin embargo, estos han sido degradados y reducidos a relictos boscosos, de los cuales no se conoce su diversidad florística en su totalidad. En este sentido el objeto del estudio fue la caracterización florística del relicto Los Lanches del bosque montano Las Palmas, ubicado al sur del distrito de Conchan, Chota, Perú. Entre los 2800 a 3000 msnm. Se identificaron 30 especies distribuidos en 27 géneros y 23 familias, de estas últimas la Lauraceae, Myrtaceae y Melastomataceae son las más representativas. Se obtuvo un coeficiente de mezcla de 0.033. El índice de Simpson de 0.89 indica una alta diversidad y un índice Shannon-Wiener de 2.28. La distribución horizontal por clases diamétricas presentó una línea con tendencia de una "J" invertida. La Weinmannia elliptica (16,63 %), Hedysomum scabrum (10,27 %), Cyathea caracasana (8,44 %) y Nectandra lineatifolia (6,03 %) presentaron un índice de valor de importancia alto. La distribución vertical en clases de altura presentó la tendencia de "j" invertida, observándose que el 20 % de especies se encuentran en los tres estratos. La Hedyosmum scabrum (98,6), Cyathea caracasana (69,8) y Weinmannia elliptica (69,8) muestran valores fitosociológicos altos. En la regeneración natural las especies más importantes son Hedyosmum scabrum (27,79 %) y Palicourea amethystina (14,77 %). Las especies con alto valor de importancia ampliado Hedyosmum scabrum (19,24 %), Weinmannia elliptica (11,44 %) y Palicourea amethystina (8,02 %).

Los montanos bosques son ecosistemas con especies endémicas valiosas; sin embargo, estos han sido degradados y reducidos a relictos boscosos, de los cuales no se conoce su diversidad florística en su totalidad. Neste sentido el objeto del estudio fue a caracterização florística del relicto Los Lanches del bosque montano Las Palmas, ubicado al no distrito de Conchan, Chota, Perú. Entre 2.800 e 3.000 msnm. Identificou 30 espécies distribuídas em 27 gêneros e 23 famílias, sendo estas ultimate la Lauraceae, Myrtaceae e Melastomataceae suas menos representativas. Obtuvo um coeficiente de mezcla de 0,033. O índice de Simpson de 0,89 indica una alta diversidad e um índice de Shannon-Wiener de 2,28. A distribuição horizontal para classes diamétricas apresentou una línea con tendencia de una "J" invertida. Weinmannia elliptica (16,63%), Hedysomum scabrum (10,27%), Cyathea caracasana (8,44%) e Nectandra lineatifolia (6,03%) apresentam um índice de importância de importancia alto. A distribuição vertical em classes de altura apresenta a tendência de "j" invertida, observando-se que 20% das espécies são encuentradas nos três estratos. Hedyosmum scabrum (98,6), Cyathea caracasana (69,8) e Weinmannia elliptica (69,8) muestran valores fitosociológicos altos. Na regeneração natural das espécies mais importantes são Hedyosmum scabrum (27,79%) e Palicourea amethystina (14,77%). Las especies con alto valor de importancia ampliado Hedyosmum scabrum (19,24%), Weinmannia elliptica (11,44%) y Palicourea amethystina (8,02%).

Understanding acute metabolic decompensation in propionic and methylmalonic acidemias: a deep metabolic phenotyping approach.

BACKGROUND: Pathophysiology of life-threatening acute metabolic decompensations (AMD) in propionic acidemia (PA) and isolated methylmalonic acidemia (MMA) is insufficiently understood. Here, we study the metabolomes of PA and MMA patients over time, to improve insight in which biochemical processes are at play during AMD. METHODS: Longitudinal data from clinical chemistry analyses and metabolic assays over the life-course of 11 PA and 13 MMA patients were studied retrospectively. Direct-infusion high-resolution mass spectrometry was performed on 234 and 154 remnant dried blood spot and plasma samples of PA and MMA patients, respectively. In addition, a systematic literature search was performed on reported biomarkers. All results were integrated in an assessment of biochemical processes at play during AMD. RESULTS: We confirmed many of the metabolite alterations reported in literature, including increases of plasma valine and isoleucine during AMD in PA patients. We revealed that plasma leucine and phenylalanine, and urinary pyruvic acid were increased during AMD in PA patients. 3-hydroxyisovaleric acid correlated positively with plasma ammonia. We found that known diagnostic biomarkers were not significantly further increased, while intermediates of the branched-chain amino acid (BCAA) degradation pathway were significantly increased during AMD. CONCLUSIONS: We revealed that during AMD in PA and MMA, BCAA and BCAA intermediates accumulate, while known diagnostic biomarkers remain essentially unaltered. This implies that these acidic BCAA intermediates are responsible for metabolic acidosis. Based on this, we suggest to measure plasma 3-hydroxyisovaleric acid and urinary ketones or 3-hydroxybutyric acid for the biochemical follow-up of a patient's metabolic stability.

Mutations in the CDSN gene cause peeling skin disease and hypotrichosis simplex of the scalp.

Peeling skin disease is a rare genodermatosis characterized by superficial exfoliation or peeling of the skin. Peeling skin disease is caused by biallelic mutations in CDSN as an autosomal recessive trait. Monoallelic mutations in CDSN have also been described in an autosomal dominant inherited genodermatosis: hypotrichosis simplex of the scalp. This disease is characterized by progressive hair loss of the scalp with onset after early childhood. Clinical data were obtained from a patient with lifelong generalized skin peeling and both his parents. The patient's parents did not suffer from skin peeling, but the mother had a history of thin scalp hair since early childhood. Mutation analysis in the patient showed compound heterozygous mutations in exon 2 of CDSN, a nonsense mutation c.598C>T (p.[Gln200*]), previously associated with hypotrichosis simplex of the scalp, and a frame-shift mutation c.164_167dup (p.[Thr57Profs*6]), previously described in peeling skin disease. The p.(Gln200*) mutation was also found in the mother of the proband. Our study strengthens the previously established link between mutations in CDSN to peeling skin disease and hypotrichosis simplex of the scalp.

[Metabolic diseases in psychiatry]. / Stofwisselingsziekten binnen de psychiatrie.

Metabolic diseases can be associated with psychiatric symptoms. We present two case histories that demonstrate the importance of correctly diagnosing a metabolic disease as being the cause of psychiatric symptoms. We also discuss which symptoms or signals may indicate a metabolic disease.

Rapid quantification of underivatized amino acids in plasma by hydrophilic interaction liquid chromatography (HILIC) coupled with tandem mass-spectrometry.

BACKGROUND: Amino acidopathies are a class of inborn errors of metabolism (IEM) that can be diagnosed by analysis of amino acids (AA) in plasma. Current strategies for AA analysis include cation exchange HPLC with post-column ninhydrin derivatization, GC-MS, and LC-MS/MS-related methods. Major drawbacks of the current methods are time-consuming procedures, derivative problems, problems with retention, and MS-sensitivity. The use of hydrophilic interaction liquid chromatography (HILIC) columns is an ideal separation mode for hydrophilic compounds like AA. Here we report a HILIC-method for analysis of 36 underivatized AA in plasma to detect defects in AA metabolism that overcomes the major drawbacks of other methods. METHODS: A rapid, sensitive, and specific method was developed for the analysis of AA in plasma without derivatization using HILIC coupled with tandem mass-spectrometry (Xevo TQ, Waters). RESULTS: Excellent separation of 36 AA (24 quantitative/12 qualitative) in plasma was achieved on an Acquity BEH Amide column (2.1×100 mm, 1.7 µm) in a single MS run of 18 min. Plasma of patients with a known IEM in AA metabolism was analyzed and all patients were correctly identified. CONCLUSION: The reported method analyzes 36 AA in plasma within 18 min and provides baseline separation of isomeric AA such as leucine and isoleucine. No separation was obtained for isoleucine and allo-isoleucine. The method is applicable to study defects in AA metabolism in plasma.

Estudio in vivo del efecto angiogénico de inhibidor de fosfodiesterasa para aplicación posterior en injerto dermoepidérmico / Angiogenic effect of sildenafil in a chicken egg model

Background: Angiogenesis is a complex process. Phosphodiesterase inhibitors may have a direct angiogenic effect. Aim: To determine if phosphodiesterase inhibitors have angiogenic properties, using a chicken egg model. Material and Methods: We used 44 fertilized chicken eggs. A methylcellulose filter was placed over their allantocorionic membrane. This preparation was instilled with different solutions. Group A (Control) received 30 u.1 of saline solution, Group B, C and D received 30 jul of a solution made of saline solution and sildenafil at different concentrations of 0.33, 1 and 3.3 u-g/ul, respectively. At day 12 the filters were removed, prepared for histologic analysis, and the number of capillaries in an area of 2250 urn² were blindly counted. Statistical analysis was made using variance analysis (ANOVA) with Bonferroni technique (p < 0.001). Results: The number of capillaries counted, per 2250 urn², in Groups A, B, C, and D were 11.1 +/- 0.5, 15.4 +/- 1.2, 16.6 +/- 0.8 and 19.2 +/- 0.9, respectively. The number of capillaries of groups B, C and D were significantly higher than those of group A (control). Moreover, there was a linear relationship between the number of capillaries and sildenafil dose (p < 0.001). Conclusions: In this experiment, sildenafil had a potent angiogenic effect.

Introducción: El proceso de angiogenesis es un proceso complejo. El uso de factores proangiogénicos está bien establecido. En este estudio se trató de averiguar si los inhibidores de fosfodiesterasa, además de su rol vasodilatador, tendrían un efecto angiogénico en los tejidos para evaluar su potencial uso terapéutico futuro en injerto dermoepidérmico. Hipótesis: Se plantea como hipótesis que el inhibidor de fosfodiesterasa tiene un efecto angiogénico directo. Material y Método: Se utilizaron 44 huevos de pollo fecundados obtenidos del Instituto de Salud Pública (ISP), a los cuales se les implantó un disco de metilcelulosa sobre la membrana alantocoriónica, a los que luego se les instiló distintas soluciones: Grupo A control, se instiló 30li1 de solución fisiológica. Grupo B, C y D 30li1 de solución con Citrato de Sildenafil a una concentración de 0,33 Lig/u.1, 1 ug/Lil y 3,3 ug/ul respectivamente. Al día 12 se removieron los discos y se fijaron para análisis histológico y se contaron de manera ciega los capilares en área de 2.250 um². Análisis estadístico con método de análisis de varianza (ANOVA) con técnica de Bonferroni (p < 0,001). Resultados: En Grupo A control, existía un promedio de 11,09 capilares/2.250um² DS 0,52. Grupo B 15,35 capilares/2.250 um² DS 1,19. Grupo C 16,62 capilares/2.250 Lim² DS 0,82. Grupo D 19,2 capilares/2.250 um² DS 0,89. Se encontró que el numero de capilares era significativamente mayor en los Grupos B, C y D en relación a control (p < 0,001). Además se observó diferencias estadísticamente significativas entre todos los grupos que recibieron tratamiento con dosis progresivas del Citrato de Sildenafil (p < 0,001). Conclusión: Se observó un efecto angiogénico del inhibidor de fosfodiesterasa utilizado, lo que podría ser aplicado en modelo para estudiar angiogénesis en injertos.

Diagnostic and prognostic tissuemarkers in clear cell and papillary renal cell carcinoma.

PURPOSE: Approximately one-third of all Renal Cell Carcinoma (RCC) patients undergoing a nephrectomy face metastatic disease. The availability of novel therapeutics for metastatic patients underscores the importance of identifying patients at risk of recurrence or patients responding well to specific therapies. Unlike clear cell RCC (ccRCC), information on biomarkers for the papillary subtype (pRCC) remains limited. In this review, we identified tissue markers that are differentially expressed between subtypes and may be of diagnostic use. In addition, markers with promising prognostic power for ccRCC and/or pRCC are described and their clinical value is discussed. MATERIALS AND METHODS: To identify diagnostic markers that differentiate between pRCC and ccRCC a Pubmed search was performed, limited to original articles published in the English language between 1990 and 2009, using the terms pRCC/papillary RCC/papillary renal cell carcinoma/papillary kidney cancer, biomarker/biomarkers, protein expression, mass spectrometry and immunohistochemistry. Prognostic markers for ccRCC and pRCC were identified using the search terms kidney cancer, renal cell carcinoma, prognostic marker, biomarker and prognosis. Only markers with independent prognostic value in multivariable analysis were included. RESULTS: 25 proteins are differentially expressed between ccRCC and pRCC, reflecting the molecularly distinct nature of these subtypes. 5 of these proteins were externally validated, which shows their diagnostic potential. Whereas 48 biomarkers with independent prognostic power have been identified for ccRCC patients, only CD44, CA9, p53, Ki67 and PCNA have shown prognostic value in multiple studies. Expression of IMP-3 and VEGF-R2 are independent predictors of survival of pRCC patients, although this is shown in single studies. CONCLUSIONS: So far 5 validated diagnostic markers are able to differentiate between ccRCC and pRCC. Few independent prognostic markers have been identified for pRCC in single studies, compared to numerous biomarkers identified for the more common ccRCC. Despite the abundance of promising markers for ccRCC, their exact role in clinical decision making still needs to be established through validation studies.

Chronic omega-3 supplementation in seizure-prone versus seizure-resistant rat strains: a cautionary tale.

Several studies have shown fatty acid supplementation to be efficacious in the treatment of attention deficit hyperactivity disorder/autism spectrum disorder (ADHD/ASD) and epilepsy. Interestingly, rats bred to be seizure-prone (Fast), unlike those bred for seizure-resistance (Slow), naturally exhibit behaviors and physiology reminiscent of ADHD/ASD in humans, suggesting a fundamental link between seizure disposition and these developmental disorders. To determine whether chronic omega-3 supplementation might ameliorate ADHD-like behaviors in the seizure-prone rat strain and/or alter natural predispositions for or against seizure in either strain, Fast and Slow weanlings were maintained on a control or omega-3-supplemented diet. As adults, rats were tested in paradigms known to elicit ADHD-like behaviors from Fast rats and then kindled from the amygdala to assess relative seizure disposition. While omega-3 supplementation did not significantly alter the relative hyperactivity, learning deficits or heightened seizure sensitivity naturally exhibited by Fast rats, it dramatically reduced their impulsivity to Slow-like levels. In contrast, typical behavioral patterns in Slow rats were largely unaffected by omega-3 supplementation yet their proclivity for seizure was greatly increased. This heightened vulnerability to seizure in Slow rats was paralleled by a drop in circulating plasma non-esterified fatty acids (NEFA) to match levels normally observed in Fast rats. These findings suggest a delicate balance between seizure predisposition and ADHD-like behaviors that can be influenced by omega-3 treatment. Further, a relationship between circulating NEFA levels and seizure susceptibility has surfaced that advocates caution when treating different genetic backgrounds with omega-3 fatty acids.

The prevalence of parasite infestation and house dust mite sensitization in Gabonese schoolchildren.

BACKGROUND: Allergic diseases seem less prevalent in communities in less developed parts of the world, where parasite infections are highly prevalent. Altogether not much is known about the association between chronic infections with tissue and blood-dwelling parasites and atopy. METHODS: In an area in Gabon endemic for blood and tissue parasites, 520 schoolchildren were parasitologically examined and skin prick-tested for a set of common environmental aeroallergens. Levels of allergen-specific IgE and polyclonal IgE were measured. RESULTS: In schoolchildren schistosome and filarial infections increased with age, whereas malaria was more prevalent in younger children. In contrast to allergen sensitization that increased with age, skin test reactivity tended to decline. The number of children with mite-specific IgE antibodies (47%) by far exceeded the number responding to skin prick testing (11%). Mite sensitization was found to be the highest in children infected with schistosomes and/or filariae whereas skin test reactivity was lowest. The multiple logistic regression showed that the risk of a positive skin test was 8-fold higher with increasing levels of mite-specific IgE but was reduced by 72% when infected with blood stage helminths. CONCLUSIONS: Chronic blood and tissue parasite infections that are often capable of modulating immune responses in the host are negatively associated with skin test reactivity in a sensitized population.

Low doses of UVB or UVA induce chromosomal aberrations in cultured human skin cells.

Chromosomal defects are frequently present in malignant and premalignant skin disorders; however, it is not known whether ultraviolet radiation from sunlight plays a role in their induction. To obtain information on the ability of ultraviolet A and ultraviolet B to induce chromosomal aberrations, cultured melanocytes and fibroblasts were exposed to physiologic doses of ultraviolet A or ultraviolet B and, for comparison, to gamma rays. As a measure of chromosomal aberrations, the formation of micronuclei was determined. To obtain sufficient statistical data on induced micronuclei and cell kinetics, a flow cytometry method has been modified and applied. The flow cytometry method analysis is based on staining the DNA with ethidium bromide and the cell membranes with 1,6-diphenyl-1,3,5,-hexatriene. We observed dose-dependent micronuclei formation after gamma or ultraviolet B irradiation in both cell types and also for ultraviolet A in fibroblasts. The yield of micronuclei induced in fibroblasts by ultraviolet A was only a factor 15 smaller than that induced by ultraviolet B (313 nm). The results indicate that 10 kJ per m2 (equivalent to 1 minimal erythema dose) of ultraviolet B and 150 kJ per m2 of ultraviolet A (0.2 minimal erythema dose) can induce 1% of micronuclei in fibroblasts, equivalent to the induction due to 0.6 Gy of gamma radiation. In conclusion, physiologic doses of sunlight can induce chromosomal aberrations at a level comparable with that observed after exposure to approximately 1 Gy of ionizing radiation. Therefore, sunlight can be considered a potential inducer of chromosomal aberrations in skin cells, which may contribute to skin carcinogenesis.

Role of the nutritional status of the litter and length and frequency of mother-litter contact bouts in prolonging lactational diestrus in rats.

Food restricting lactating rat dams over the first 2 weeks of lactation results in a prolongation of the period of lactational diestrus. Such food restriction has not only a direct effect on the dam but also the pups are undernourished, and the pattern of dam-litter contact is also changed. In a series of studies, we investigated the effects of nursing undernourished pups and the change in dam-litter interaction on the prolongation of lactational diestrus. While nursing undernourished pups in the last 2 weeks of lactation is sufficient to extend lactational diestrus in ad lib-fed dams nursing well-nourished pups in the last 2 weeks of lactation is not necessary for the prolongation of lactational diestrus seen in food-restricted dams. Further, neither nursing underfed pups nor increased nest time in the first 2 weeks postpartum are necessary factors for the prolongation of lactational diestrus in food-restricted dams.

Detection of thin a-Si:H antireflective coatings on oxidized c-Si by resonant-detected spectroscopic ellipsometry.

The cleaning procedures applied in the wafer processing of thin a-Si:H overlayers have been monitored by spectroscopic ellipsometry. By selecting a suitable sample configuration and exploiting a tunable angle of incidence, we show that spectroscopic ellipsometry is extremely sensitive to small modifications at the vacuum-a-Si:H interface induced by the cleaning procedures. Experimental results are presented on the characterization of thin (3-12-nm) a-Si:H films on top of thermally oxidized crystalline silicon. Submonolayer sensitivity of the ellipsometric measurement to changes in a-Si:H film thickness is shown.

Nest temperature: effects on maternal behavior, pup development, and interactions with handling.

These studies compared the patterns of mother-young contact under different thermal environments and assessed the implications of the differing patterns of contact for pup development and the dam's behavior. In the first experiment, the warm surface dramatically reduced the total amount of contact time between dams and litters and the dam's food intake, but the effects on the pups were limited to smaller adrenal glands. A replication of the first experiment in which daily weighing and handling of the pups was eliminated produced no differences in development. In a third experiment, during which dams had access to a warm surface outside of the next area and the daily weighing and handling was resumed, the pups showed smaller adrenal glands, lower body temperatures and less thermoregulatory ability. A comparison of results suggests that handling increased the weight of adrenal glands of pups reared under the unmanipulated condition, but not the warm-rearing condition.

Reverse-phase liquid chromatographic determination of benzoic and sorbic acids in fresh cheese.

The sorbate and benzoate contents of commercial fresh cheese (quarg) samples are determined by reverse-phase liquid chromatography following extraction with a methanol-acetate buffer pH 4.5 mixture (37 + 63). The mobile phase is acetonitrile-acetate buffer pH 4.5 (20 + 80), the effluent flow rate is maintained at 1.0 mL/min, and the detector is set at 232 nm. Recoveries from quarg spiked at the 5-50 mg/kg level ranged from 95 to 99%, which compares favorably with methods previously published. Precision averaged 2-5% RSD, whereas the limit of detection was 0.3 mg/kg (sorbic acid) and 1.0 mg/kg (benzoic acid).

Neuroendocrine basis of thermally regulated maternal responses to young in the rat.

Over the first two weeks postpartum there is a decline in the amount of time that the rat dam spends with her young, resulting from a decrease in the duration of each nest bout. The duration of each nest bout is limited by the rate of rise of maternal temperature when she huddles with her litter. This pattern of mother-young contact is dependent on the dam's hormonal status, because adrenalectomised dams fail to show the expected decline in mother-young contact over time. Ovariectomy, on the other hand, does not have any effect on this behavior. Replacement therapy with glucocorticoids or placing the dam in a warm (25 degrees C) ambience reinstates the normal pattern of mother-litter contact in adrenalectomised-ovariectomised dams. These data suggest that the elevated level of serum glucocorticoids in lactating dams affects maternal behavior by increasing maternal heat load, thereby making the dam vulnerable to an acute rise in temperature when huddling with her young. Prolactin suppression also results in an increase in contact time between mother and young, but only in the second week postpartum. The effects of prolactin suppression are reversed by progesterone replacement or placing prolactin-suppressed females in a warm ambience. However, progesterone is ineffective in restoring the normal pattern of mother-litter contact in adrenalectomised females. These findings suggest that progesterone raises the thermal set point, thereby permitting the thermogenic effects of glucocorticoids to occur.

Effects of litter age, litter size, and ambient temperature on the milk ejection reflex in lactating rats.

Under a number of circumstances the duration of mother-young contact in the rat can be drastically reduced while pup growth is maintained. We investigated the possibility that under some of these conditions the timing of milk delivery is changed. We assessed the time of onset and pattern of milk delivery over a nest bout in litters of two different ages (Day 4 or Day 10) and three different sizes (4, 8, or 12 pups). Ambient temperature fluctuated over the course of the study and was found to correlate significantly with the latency to the first milk ejection (ME). Specifically, the warmer the ambient temperature, the quicker the first ME occurred. Durations between successive MEs correlated with ambient temperature in a similar fashion. Analysis of covariance revealed that the onset of the first ME occurred earlier in Day 10 litters than in Day 4 litters, but litter size had no effect. Durations between successive MEs were not affected by either litter age or litter size. These data indicate one possible mechanism by which adequate milk delivery can be maintained despite some reduction in mother-young contact.