Understanding the role of haptoglobin in psoriasis: effects of ultraviolet B.

BACKGROUND: Haptoglobin (Hp) is one of the acute phase proteins, whose main function is to bind free haemoglobin (Hb) and transport it to the liver for degradation and iron recycling. In addition to its role as an Hb scavenger, Hp has been shown to behave as an anti-inflammatory, antioxidant and angiogenic factor. We previously investigated the role of Hp in the pathogenesis of psoriasis, and found that it displays some structural modifications that might be associated with protein function in the disease. Phototherapy is an efficacious treatment for psoriasis, although the biological mechanisms by which phototherapy improves psoriasis are still unclear. AIM: To investigate the effects of ultraviolet (UV)B on Hp to clarify the role of Hp in psoriasis. METHODS: Expression of the genes encoding Hp, interleukin (IL)-6 and IL-10 was assessed in UVB-irradiated and unirradiated HaCaT cells. The biological significance of Hp modulation of UVB treatment was confirmed by ELISA and Western blotting. The Hp gene and protein expression in the skin of patients with psoriasis was also investigated. RESULTS: In vitro results showed that UVB modulated IL-6 and IL-10 gene expression and Hp gene and protein expression in HaCaT cells. The in vivo data also showed that Hp levels were increased in the skin of patients with psoriasis compared with healthy controls. CONCLUSIONS: UVB irradiation was able to modulate Hp production in immortalized keratinocytes. The higher levels of Hp in vivo in both lesional and nonlesional skin suggest that it might have a role in the pathogenesis of the disease.

Intractable diarrhea in infancy and molecular analysis: We are beyond the tip of the iceberg.

BACKGROUND: Intractable diarrhea (ID) could be defined as a syndrome of severe chronic diarrhea associated with malnutrition not easily resolved by conventional management. AIMS: To provide an overview on etiology and management of ID patients in Italy in the last 12 years. METHODS: The members of Italian Society for Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) enrolled all ID patients seen between January 1, 2011 and December 31, 2022. RESULTS: 69 children were enrolled (49 M, 20 F; median age at ID onset 9.5 days) from 7 tertiary care pediatric centers. Overall 62 patients had genetic diseases; 3 had infantile Inflammatory Bowel Disease and 1 autoimmune enteropathy in absence of genetic mutations; 2 undefined ID. Defects of intestinal immune-related homeostasis caused ID in 29 patients (42 %). CONCLUSION: ID is a rare but challenging problem, although the potential for diagnosis has improved over time. In particular, molecular analysis allowed to identity genetic defects in 90 % of patients and to detect new genetic mutations responsible for ID. Due to both the challenging diagnosis and the treatment for many of these diseases, the close relationship between immune system and digestive tract should require a close collaboration between pediatric immunologists and gastroenterologists, to optimize epidemiologic surveillance and management of ID.

Ultrasound scanning in infants with biliary atresia: the different implications of biliary tract features and liver echostructure.

OBJECTIVE: To evaluate ultrasonographic features of the liver and biliary tree, including the presence of the triangular cord, in infants with biliary atresia and to analyze the correspondence between hepatic echostructure and histological aspects of the liver. MATERIALS AND METHODS: 35 consecutive infants (19 males) with documented diagnosis of biliary atresia were included. Ultrasonography evaluation, performed at a mean age of 63.1 ± 34.9 days, was focused on the extrahepatic bile ducts, characteristics of the gallbladder and liver, and the presence of the triangular cord. Liver biopsies were examined with particular regard to the presence and severity of fibrosis. RESULTS: On ultrasound, the gallbladder was not seen in 11 (31 %) cases, while in the remaining 24 patients the gallbladder was regular in 6 patients and irregular in 18 cases. The triangular cord was identified in 9 (26 %) of 35 patients. In 21 patients the liver echostructure appeared normal, while in 14 infants the liver parenchyma was more echogenic and coarse than normal. Liver biopsy showed signs of cirrhosis or fibrosis in all cases, including patients with a normal hepatic echostructure. CONCLUSION: Although the triangular cord was visualized in one-fourth of the infants with biliary atresia, abnormalities of the gallbladder on ultrasound (absence or abnormalities of length/shape) were detected in 83 % of the patients. Therefore, ultrasound evaluation of the liver and biliary tree plays an important role in suspecting biliary atresia. On the other hand, a low correspondence between liver echostructure aspects and the presence and severity of fibrosis at liver biopsy was identified. Therefore, severe liver disease in infants with biliary atresia cannot be excluded only on the basis of ultrasound findings.

Teduglutide in pediatric intestinal failure: A position statement of the Italian society of pediatric gastroenterology, hepatology and nutrition (SIGENP).

In recent years, the spectrum of possible treatments for Intestinal Failure (IF)-Short Bowel Syndrome (SBS) has been enriched by the implementation of GLP-2 analogues. In Italy, teduglutide (Ted), an analogue of GLP-2, was approved in January 2021 by the Italian Regulatory Agency for Drugs (AIFA) for IF-SBS patients ≥1 year old. According to the Agency indications, Ted can now be prescribed by regional reference centers, with costs fully charged to the National Health Service. Following pediatric-use approval in our country and in light of scarce evidence in childhood, the pediatric network for IF of the Italian Society for Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) planned to share management methods of Ted in pediatric IF. The main purpose was to identify the best candidates from a cost-effective perspective. Thus, focusing on available literature and on expert opinions, the present position statement provides consensus-based recommendations on the use of Ted for pediatric gastroenterologists and nutritionists treating children with SBS.

Novel missense mutations and unexpected multiple changes of RYR1 gene in 75 malignant hyperthermia families.

Malignant hyperthermia (MH) is an autosomal dominant pharmacogenetic disorder of skeletal muscle characterized by disturbance of intracellular calcium homeostasis in the sarcoplasmic reticulum. Mutations of the ryanodine receptor 1 (RYR1) gene account for most cases, with some studies claiming up to 86% of mutations in this locus. However, RYR1 gene is large and variants are common even in the normal population. We examined 54 families with MH susceptibility and 21 diagnosed with equivocal MH. Thirty-five were selected for an anesthetic reaction, whereas the remainder for hyperCKemia. In these, we studied all 106 exons of the RYR1 gene. When no mutation was found, we also screened: sodium channel voltage-gated, type IV alpha subunit (SCN4A), calcium channel voltage-dependent, L type, alpha 1S subunit (CACNA1S), and L-type voltage-gated calcium channel alpha 2/delta-subunit (CACNL2A). Twenty-nine different RYR1 mutations were discovered in 40 families. Three other MH genes were tested in negative cases. Fourteen RYR1 amino acid changes were novel, of which 12 were located outside the mutational 'hot spots'. In two families, the known mutation p.R3903Q was also observed in malignant hyperthermia-nonsusceptible (MHN) individuals. Unexpectedly, four changes were also found in the same family and two in another. Our study confirms that MH is genetically heterogeneous and that a consistent number of cases are not due to RYR1 mutations. The discordance between in vitro contracture test status and the presence of a proven causative RYR1 mutation suggests that the penetrance may vary due to as yet unknown factors.

Hg bioavailability and impact on bacterial communities in a long-term polluted soil.

Different soil samples characterised by a long-term Hg-pollution were studied for Hg total content, fractionation, phytotoxicity and influence on the bacterial community. Hg pollution ranged from 1 to 50 mg kg(-1) and most of it was speciated in scarcely soluble forms. In agreement with this, the biochemical quality indexes were investigated (biomass, enzyme activities) and the bacterial community (viable heterotrophic (VH) bacteria, functional diversity) apparently was not influenced by the degree of Hg pollution. In particular, the investigated soils exhibited a low percentage of Hg-resistant (Hg(R)) bacteria ranging from less than 0.001% to 0.25% of the VH and the addition of available Hg in the form of HgCl(2) induced an enrichment of resistant Hg(R) populations. The general biodiversity of the bacterial community was evaluated by denaturing gradient gel electrophoresis of DNA of Hg spiked soil microcosms and of control soils. Hg(R) bacteria capable to grow in a minimal medium containing HgCl(2) were also isolated and identified. MerA and merB gene PCR fragments were obtained from different Hg(R) strains and the range of similarities at the DNA level and at the deduced amino acid level showed that they carried mercuric reductase and lyase. Differently from bacteria, some influence of soil Hg content on seeds' germination and root elongation was observed for Lepidium sativum L. and Solanum lycopersicum L. In conclusion, most of the Hg in these long-term polluted soils was scarcely mobile and available and did not significantly influence the soil bacterial community. The risk of potential Hg remobilization over time, that could be naturally favoured by the activity of plant roots or other inorganic processes occurring in soil, can be extenuated since bacterial community was resistant and resilient to subsequent Hg stress.

Is resistin a link between highly active antiretroviral therapy and fat redistribution in HIV-infected children?

OBJECTIVES: To assess the features of fat redistribution, detected by clinical and ultrasound (US) methods, and the presence of metabolic disorders in HIV-infected children undergoing antiretroviral therapy. To evaluate if serum levels of resistin, a hormone produced only by visceral adipose tissue, are a marker of fat redistribution in these patients. DESIGN AND METHODS: Forty-five consecutive symptomatic HIV-infected children were considered for inclusion in the study. Patients were enrolled if treated for at least 6 months with antiretroviral therapy with or without protease inhibitor (PI) and if compliant to the study protocol. Patients were evaluated for: anthropometric measures, fat redistribution by clinical and US methods, serum lipids, parameters of insulin resistance by homeostasis model assessment for insulin resistance, serum resistin levels by an enzyme-linked immunosorbent assay. RESULTS: Eighteen children fulfilled the inclusion criteria and were enrolled in the study. Twelve (66%) children had clinical and/or US evidence of fat redistribution; 9 (75%) of them were on PI therapy; only 3 of 6 children without fat redistribution were on PI therapy (p<0.05). Serum lipids and insulin resistance parameters did not differ between children with or without fat redistribution. There was a highly significant linear correlation between visceral fat detected by US and circulating resistin levels (r=0.87; p<0.0001). CONCLUSIONS: Fat redistribution occurred in most HIV-infected children undergoing PI therapy. Because serum resistin levels reflect the amount of visceral fat, they could be considered a sensitive marker of fat redistribution in HIV-infected children.

Update on coeliac disease and type 1 diabetes mellitus in childhood.

The increased prevalence of coeliac disease (CD) among children with type 1 diabetes mellitus (DM1) implies that there is more than a simple association. A link between the gut immune system and DM1 has been suggested both in animal models and in humans. We review the literature on the epidemiology and genetic and clinical aspects shared by these two diseases and speculate on the role of gluten on the possible relationship between CD and DM1, on the basis of recent animal and human studies. The data suggest a failure in oral tolerance mechanisms in DM1 other than that in CD. It remains to be understood why only a small proportion of patients with DM1 proceed to the production of coeliac-associated antibodies and to overt enteropathy.

Migration test of Bisphenol A from polycarbonate cups using excitation-emission fluorescence data with parallel factor analysis.

Bisphenol A (BPA) is one of the most largely produced chemical in the world; it is used to make plastics and epoxy resins. The endocrine disruptor potential of BPA is well known, but recent researches suggest a relationship between chronic exposure to BPA, genotoxic activity and epigenetic modifications. The main source of exposure to BPA includes food contact materials (FCM). Thus simple and robust test methods are needed to improve the migration test of BPA. In this work, a non-separative, easy, fast and inexpensive spectrofluorimetric method based on the second order calibration of excitation-emission fluorescence matrices (EEMs) was proposed for the determination of BPA. For the first time, molecular fluorescence was used to identify unequivocally and quantify BPA. Trilinearity of the data tensor guarantees the uniqueness of the solution obtained through parallel factor analysis (PARAFAC), so one factor of the decomposition matches up with BPA even if other fluorophores are in the test sample. The effect of four experimental factors of the procedure on the figures of merit and the unequivocally identification was investigated by means of a D-optimal design and PARAFAC calibration. The method is linear and accurate in the range 0-720µgL-1. The decision limit CCα and detection capability CCß are 6.63µgL-1 and 18.85µgL-1 respectively (with probabilities of false positive and false negative fixed at 0.05). Finally the proposed method was applied to carry out a migration test from two polycarbonate cups, using 3% (w/v) acetic acid in aqueous solution as food simulant. The migrated amount of BPA was found to be 688.7µgL-1 (n=5) for the first cup and 710.5µgL-1 (n=4) for the second one, above the specific migration limit set by EFSA (European Food Safety Authority).

Italian pediatric nutrition survey.

INTRODUCTION: the prevalence of malnutrition in children and its impact on clinical outcomes is underrecognized by clinicians in Italy as well as worldwide. A novel definition of pediatric malnutrition has been recently proposed by a working group of the Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), based on the correlation between illness and the use of zscores of anthropometric measurements. AIM: to investigate the prevalence of malnutrition and related nutritional support among hospitalized children in Italy, in a nationwide survey performed in a single day (16/4/2015). METHODS: an open access website (http://nday.biomedia.net) was used to collected data from 73 hospitals and 101 wards in 14 Italian regions (1994 patients). Anonymous information was collected on hospitals' characteristics, patient's anthropometry, admission diagnosis, presence of chronic diseases and use of nutritional support: oral nutritional supplements (ONS), enteral nutrition (EN) or parenteral nutrition (PN). Z-scores of anthropometric measurements, calculated with Epi Info 7.1.5, defined nutritional status: wasting was identified by BMI or Weight-for-Length z-score (<-1 mild, <-2 moderate, <-3 severe), stunting by Height-for-Age Z-score <-2. WHO 2006 and CDC 2000 growth charts were used respectively for children younger and older than 2 years old. RESULTS: 1790 complete records were obtained for hospitalized patients aged 0-20 years, with median age 6.16 (0.1-20 years and 53.3% males). 52.9% were aged 0-6 years and 58.8% of children suffered from chronic diseases. Wasting was detected in 28.7% of the total sample with higher occurrence observed in age ranges 0-6 and 14-20 years, while 17.3% of patients showed stunting; surprisingly almost 27% of them were aged 0-2. A ranking of the admission diagnosis with the highest rate of malnutrition was complied. The prevalence of wasting was significantly (p < 0.005) higher amongst children with chronic diseases (34.1% vs. 27.1%); stunting prevalence tripled in patients with chronic disease (24.5% vs. 8.3%). Only 23.5% of malnourished children (17%, 25.6% and 36.7%, respectively mild, moderate and severe malnutrition) received nutritional support: 11.7% received oral nutrition supplements (ONS, modular or complete), 11.5% enteral nutrition (EN, 6.4% via nasogastric tube, 5.1% via gastrostomy) and 6.8 % received parenteral nutrition (PN); in some patients a combination of two. Nutritional support is more commonly used among stunting patients, 39.5% of children under treatment. CONCLUSION: Malnutrition of any grade was observed in nearly 1/3 and stunting in 17% of the reported hospitalized children, and it is likely to be underrecognized as the nutritional support reached only a small part of the malnourished children.

Rank-based biomarker index to assess cadmium ecotoxicity on the earthworm Eisenia andrei.

A proper soil risk assessment needs to estimate the processes that affect the fate and the behaviour of a contaminant, which are influenced by soil biotic and abiotic components. For this reason, the measurement of biomarkers in soil bioindicator organisms, such as earthworms, has recently received increasing attention. In this study, the earthworm Eisenia andrei was used to assess the pollutant-induced stress syndrome after exposure to sublethal concentrations of Cd (10 or 100 µg g(-1)) in OECD soil, after 14 d of exposure. Cadmium bioaccumulation and potential biomarkers such as catalase (CAT), hydrogen peroxide (H2O2), glutathione-S-transferase (GST), malondialdehyde (MDA), phenoloxidase (PO), metallothioneins (MTs) and genotoxic damage were determined. Results suggested that the exposure to 10 and 100 µg g(-1) Cd significantly increased Cd bioaccumulation, MTs and MDA; 100 µg g(-1) Cd contamination evidenced significantly higher values of H2O2 content and PO activity; CAT activity was inhibited at the higher concentration while GST and Comet assay did not show any significant differences from the control. Rank-based biomarker index showed that both different contaminated soils had an effect on the earthworms and allowed to validate the ecotoxicological relevance of this battery of biomarkers for a promising integrated multi-marker approach in soil monitoring and assessment.

Treatment of chronic hepatitis C in children with pegylated interferon and ribavirin: the impact of dose.

INTRODUCTION: In the last years children with chronic hepatitis C (CHC) have been treated with Pegylated Interferon α (PEG-IFNα) and ribavirin (RBV). Treatment can cause several side effects that require reduction or interruption of therapy. The relationship between dose of PEG-IFNα and response to therapy has not been clearly evaluated. Aim of this study was to evaluate the impact of the dose of PEG-IFNα2b and RBV on the efficacy of therapy. PATIENTS AND METHODS: All children with CHC treated with PEG-IFNα2b and RBV, observed at the Paediatric Liver Unit of University Federico II of Naples from 1996 to 2006 were evaluated. RESULTS: Sixteen children with CHC treated with combined therapy were enrolled. Seven out of 16 patients (43.7%) achieved rapid virological response; 13/16 patients (81.2%) achieved early virological response; 5/16 patients (31.25%) relapsed; 1 patient resulted non responder. According to percentage of expected dose, our patients were divided into two groups: the first group included 7 patients that performed an overall dosage of PEG-IFNα2b ≥ 75% of the scheduled full dose; the second group included 9 patients that performedm PEG-IFNα2b dose < 75% of scheduled full dose. No difference was noted in terms of sustained virological response. CONCLUSIONS: Modifications of therapy due to PEG-IFNα-related adverse events are frequent in children with CHC, but dose adjustments do not seem to impair efficacy of therapy.

In vivo assessment of an industrial waste product as a feed additive in dairy cows: Effects of larch (Larix decidua L.) sawdust on blood parameters and milk composition.

When larch (Larix spp.) is processed in the wood industry, the sawdust is currently disposed of as waste or used as combustible material, even though it is rich in biologically active compounds. In this study the effect of larch sawdust supplementation on blood parameters as well as milk composition was examined in healthy mid-lactating dairy cows. Twenty-four multiparous Italian Friesian dairy cows were assigned to groups receiving either 300 g/day/cow of larch sawdust or a control diet, and treatments were continued for a 20 day period. Milk parameters were unaffected by treatment. A lower plasma total protein concentration was observed and can be attributed to a decrease in globulin concentration. A lower plasma urea concentration was also detected in the larch group. Moreover, biomarkers of liver function were influenced by the treatment. Total bilirubin was lower in larch-treated animals, and cholesterol tended to be lower. In addition, an interaction between day and treatment was observed for very low density lipoprotein. The concentration of other parameters, including reactive oxygen metabolites, superoxide dismutase, glutathione peroxidase and nitrotyrosine, did not differ between treatments. The observed benefits, together with the good palatability, make larch sawdust a promising candidate for the development of beneficial feed supplements for livestock. Further studies will be useful, particularly to evaluate its efficacy in different health conditions.

Synthesis of ascorbate and urate in the ovary of water buffalo.

Blood flow interruption is associated with oxygen depletion and loss of factors for function and survival in downstream tissues or cells. Hypoxia and absence of gonadotropins trigger apoptosis and atresia in the ovary. We studied the antioxidant response of follicular cells to plasma deprivation in ovaries dissected from water buffalo. Aliquots of follicular fluid were aspirated from each antral follicle, before and during incubation of the ovaries at 39 degrees C. Urate, ascorbate, retinol and alpha-tocopherol in the fluid were, titrated by High Performance Liquid Chromatography (HPLC) with spectrophotometric or spectrofluorimetric detection. The total antioxidant capacity of follicular fluid was determined as absorbance decrease, following addition of a source of radical chromophores. The more the incubation progressed, the higher levels of urate, ascorbate and total antioxidant capacity were found. Conversely, changes in concentration of the liposoluble antioxidants were not observed. Ascorbate synthesizing activity in the follicle was demonstrated by detecting the enzyme L-gulono-gamma-lactone oxidase in microsomes prepared from granulosa cells. These cells were also analyzed for the expression of the enzyme CPP32. The enzyme level, measured as DEVD-p-nitroanilide cleaving activity, was found related with the immunoreactivity to anti-CPP32 antibodies. Negative correlation between the enzyme activity (which is known to be induced by peroxynitrite) and the follicular level of urate (which scavenges peroxynitrite) was also observed. The amount of nitrotyrosine, a product of peroxynitrite attack on proteins, was measured in follicular fluids by Enzyme Linked ImmunoSorbent Assay (ELISA). This amount was found positively correlated with the CPP32 activity, and negatively correlated with the urate level in follicular fluid. Alterations in concentrations of ascorbate or urate may be associated with oxidative stress during follicular atresia.

Evaluation of the antioxidant response in the plasma of healthy or hypertensive subjects after short-term exercise.

Reactive oxygen species are produced during exercise. The antioxidants prevent or limit tissue damages by these species in physiological conditions. In particular, ascorbate and urate scavenge peroxynitrite, which can alter the function of many molecules, including the lecithin-cholesterol acyltransferase (LCAT) enzyme involved in reverse cholesterol transport. The aims of the present study were to compare the plasma antioxidant response to an ergometric test (ET) in hypertensive and healthy subjects, evaluate the exercise-dependent nitrosative stress in plasma, and assess whether the LCAT activity is altered by the exercise. Plasma samples, prepared before and after ET from hypertensive or healthy volunteers, were analysed for their levels of ascorbate, urate, alpha-tocopherol, retinol, nitrotyrosine, and LCAT activity. The alpha-tocopherol and retinol levels did not significantly change in both groups during exercise, while the ascorbate level changed displaying higher increase in controls (+38.8%) than in hypertensives (+17.2%). In these patients, during ET, the urate and nitrotyrosine levels changed more than in normotensives (+13.5 and +40.6% vs -3.1 and +25.2%, respectively). The antioxidants effectively prevented loss or reduction of LCAT activity, as it was similar in hypertensives and normotensives, and did not change after ET. The results demonstrate that exercise is associated with enhanced protein nitrosation, and suggest that the ascorbate or urate levels increase to limit oxidative damage.

Management of diabetes in childhood: are children small adults?

Diabetes in childhood is the most common chronic disease and generally fits the type 1 category, even though other forms of non-autoimmune diabetes are now emerging in this age. At variance with adults, children and adolescents undergo physiological process, which may frequently require adjustments of clinical management of diabetes. Moreover, the hormonal and psychological changes during puberty may be crucial in conditioning management. Furthermore, common illnesses frequently affecting children may also destabilise metabolic control. Consequently, education in children is the cornerstone of treatment. This review focuses on the several and peculiar aspects of practical management of diabetes in paediatric age, which require professional figures such as paediatricians, nurses, dieticians, psychologists, social assistants originally trained in paediatric area, able to deal with the age-related medical, educational, nutritional and behavioural issues of diabetes.

Estradiol esterification in the human preovulatory follicle.

In the preovulatory follicle, the LH surge stimulates progesterone production, reduces estradiol synthesis, and scales up the permeability of the blood-follicle barrier. The purpose of this study was to investigate whether the extent of these changes is correlated with the levels of estradiol, estradiol esters, and cholesteryl esters in the follicular fluid. The follicular levels of progesterone, estradiol, estradiol linoleate, cholesterol, and cholesteryl linoleate were measured by HPLC. The estradiol linoleate/estradiol ratio, which reflects the efficiency of in vivo estradiol esterification, and the cholesteryl linoleate/cholesterol ratio were calculated and found negatively correlated. The estradiol level was positively correlated with the cholesteryl linoleate/cholesterol ratio while negatively correlated with the estradiol linoleate/estradiol ratio. The in vitro activity of lecithin-cholesterol acyltransferase, the enzyme esterifying both cholesterol and estradiol, was assayed by incubating the fluid with labeled substrates. This activity was not correlated with either the estradiol linoleate/estradiol or the cholesteryl linoleate/cholesterol ratio. The enzyme K(m) and V(max) values were lower with estradiol than with cholesterol. Higher estradiol linoleate/estradiol ratios and lower cholesteryl linoleate/cholesterol ratios were associated with higher level of Haptoglobin penetration into the follicle. This level, which was determined by ELISA, was found increased with increased progesterone concentration and, therefore, used as a marker of the LH-stimulated permeability of the blood-follicle barrier. Our data suggest that early preovulatory follicles contain more cholesteryl esters and less estradiol esters than follicles closer to ovulation.

Lecithin-cholesterol acyltransferase activity during maturation of human preovulatory follicles with different concentrations of ascorbate, alpha-tocopherol and nitrotyrosine.

The enzyme lecithin-cholesterol acyltransferase (LCAT) transfers an acyl chain from lecithin to cholesterol or oestradiol, thus playing a crucial role in reverse cholesterol transport and follicular synthesis of potent long-lived oestrogens. The mechanism of catalysis is biphasic, as it is based on a phospholipase and an esterifying activity. Sulfhydryl groups were previously reported to be required for the esterification step. Lecithin-cholesterol acyltransferase has previously been shown to be inhibited by thiol oxidants such as peroxynitrite. Peroxynitrite also converts tyrosine to nitrotyrosines. In the present study, high levels of nitrotyrosine associated with low LCAT activity, and vice versa, were found in human preovulatory follicular fluids. Follicular fluids were also analysed for oestradiol (E) and progesterone (P) concentrations. The E/P ratio, which decreases as ovulation approaches, was used to evaluate the maturation status of each follicle. Enzyme activity was negatively correlated with the E/P ratio. Ascorbate (Asc) and alpha-tocopherol (Toc) were titrated in follicular fluid and plasma to evaluate their accumulation or consumption in the follicle. High LCAT activity was found in follicular fluids where Asc and Toc had accumulated, whereas lower activity was associated with Asc and Toc consumption. The consumption of both antioxidants was positively correlated with the E/P ratio. The results suggest that as follicle maturation progresses, Toc and Asc concentrations increase in follicular fluid, thus protecting LCAT from oxidative damage and loss of activity.

Adrenocortical tumor in a boy: final height is not impaired despite a severe advancement of bone age.

The long-term sequelae on the growth pattern in successfully resected virilizing adrenal tumors (ACT) have not been clearly defined. We report on 10 years follow-up of a boy with virilizing ACT until the attainment of final height. This is the first clinical description in a boy with a marked advancement of bone age, indicating that despite advanced physical and skeletal maturity the prognosis on growth is good, provided that regression of virilization is obtained.