Effect of simulated extreme rainfall on the vegetative phenology of perennial and annual herbaceous plants from a Brazilian dry forest.

Detecting changes in the phenological responses of herbaceous species as a function of predicted climate change is important for forecasting future scenarios for the functioning of dry tropical forests, especially when predicting an increase in the frequency and intensity of extreme droughts. Because of the sensitivity of plants to water availability, our study hypothesizes that if years become drier or wetter, herbaceous plants will synchronously change the onset, duration, and intensity of their vegetative phenophases. We used a historical series of 60 years of precipitation observations for the Caatinga vegetation to define daily average of precipitation for rainy (Twet), median (Tcontrol), and dry (Tdry) years. We simulated past average daily rainfall (Twet, Tcontrol, and Tdry) while growing two herbaceous perennials and two herbaceous annuals. We monitored plant growth and measured the activity (absence or presence) and intensity of vegetative phenophases. We used circular statistical analysis to assess differences between treatments. Our results revealed that leaf production was seasonal but relatively uniform for perennial species and highly seasonal (wet season) for annual species. Simulated dry years induced lower leaf emergence concentrated over a few months in annual species, but this effect was more strongly significant in one of the two perennial species. Both annual and perennial species can experience delayed and less intense leaf abscission during the rainy season in years with below-average precipitation. In contrast, large voluminous rains in years with above-average precipitation can accelerate and intensify the process of leaf renewal. If future precipitation reductions occur, the changes in phenological response indicate that the cover of annual and perennial herbaceous species in this study will likely decrease, altering the landscape and functioning of dry tropical forests. However, the potential trade-offs observed may help populations of these species to persist during years of severe drought in the Caatinga.

The geographical distribution and socioeconomic risk factors of COVID-19, tuberculosis and leprosy in Fortaleza, Brazil.

BACKGROUND: Fortaleza (Brazil) is high endemic for coronavirus disease 2019 (COVID-19), tuberculosis (TB) and leprosy. These three diseases share respiratory droplets through coughing or sneezing as the main mode of transmission but differ in incubation time, with COVID-19 having a short and leprosy a long incubation time. Consequently, contacts of a patient are at higher risk of infection and developing these diseases. There might be scope for combined preventive measures, but a better understanding of the geographical distribution and relevant socioeconomic risk factors of the three diseases is needed first. This study aims to describe the geographic distribution of COVID-19, TB and leprosy incidence and to identify common socioeconomic risk factors. METHODS: The total number of new cases of COVID-19, TB and leprosy, as well as socioeconomic and demographic variables, were retrieved from official registers. The geographical distribution of COVID-19, TB and leprosy rates per neighbourhood was visualised in Quantum GIS, and spatial autocorrelation was measured with Moran's I in GeoDa. A spatial regression model was applied to understand the association between COVID-19, TB, leprosy rates, and socioeconomic factors. RESULTS: COVID-19 and TB showed a more homogenous distribution, whereas leprosy is located more in the south and west of Fortaleza. One neighbourhood (Pedras) in the southeast was identified as high endemic for all three diseases. Literacy was a socioeconomic risk factor for all three diseases: a high literacy rate increases the risk of COVID-19, and a low literacy rate (i.e., illiteracy) increases the risk of TB and leprosy. In addition, high income was associated with COVID-19, while low income with TB. CONCLUSIONS: Despite the similar mode of transmission, COVID-19, TB and leprosy show a different distribution of cases in Fortaleza. In addition, associated risk factors are related to wealth in COVID-19 and to poverty in TB and leprosy. These findings may support policymakers in developing (partially combined) primary and secondary prevention considering the efficient use of resources.

miRNA signatures in childhood sarcomas and their clinical implications.

Progresses in multimodal treatments have significantly improved the outcomes for childhood cancer. Nonetheless, for about one-third of patients with Ewing sarcoma, rhabdomyosarcoma, or osteosarcoma steady remission has remained intangible. Thus, new biomarkers to improve early diagnosis and the development of precision-targeted medicine remain imperative. Over the last decade, remarkable progress has been made in the basic understanding of miRNAs function and in interpreting the contribution of their dysregulation to cancer development and progression. On this basis, this review focuses on what has been learned about the pivotal roles of miRNAs in the regulation of key genes implicated in childhood sarcomas.

Analysis of real-time mixture cytotoxicity data following repeated exposure using BK/TD models.

Cosmetic products generally consist of multiple ingredients. Thus, cosmetic risk assessment has to deal with mixture toxicity on a long-term scale which means it has to be assessed in the context of repeated exposure. Given that animal testing has been banned for cosmetics risk assessment, in vitro assays allowing long-term repeated exposure and adapted for in vitro - in vivo extrapolation need to be developed. However, most in vitro tests only assess short-term effects and consider static endpoints which hinder extrapolation to realistic human exposure scenarios where concentration in target organs is varies over time. Thanks to impedance metrics, real-time cell viability monitoring for repeated exposure has become possible. We recently constructed biokinetic/toxicodynamic models (BK/TD) to analyze such data (Teng et al., 2015) for three hepatotoxic cosmetic ingredients: coumarin, isoeugenol and benzophenone-2. In the present study, we aim to apply these models to analyze the dynamics of mixture impedance data using the concepts of concentration addition and independent action. Metabolic interactions between the mixture components were investigated, characterized and implemented in the models, as they impacted the actual cellular exposure. Indeed, cellular metabolism following mixture exposure induced a quick disappearance of the compounds from the exposure system. We showed that isoeugenol substantially decreased the metabolism of benzophenone-2, reducing the disappearance of this compound and enhancing its in vitro toxicity. Apart from this metabolic interaction, no mixtures showed any interaction, and all binary mixtures were successfully modeled by at least one model based on exposure to the individual compounds.

Modulation of CYP3A4 activity alters the cytotoxicity of lipophilic phycotoxins in human hepatic HepaRG cells.

The aim of this study was to investigate (i) the cytotoxic effects of lipophilic phycotoxins, including okadaic acid (OA) and dinophysistoxin-1 and -2 (DTX-1 and DTX-2), pectenotoxin-2 (PTX-2), yessotoxin (YTX), spirolide (SPX), and azaspiracids-1, -2 and -3 (AZA-1, AZA-2 and AZA-3), in human HepaRG cells using a multiparametric high content analysis approach, (ii) the ability of nine lipophilic phycotoxins to act as PXR agonists in a HepG2-PXR cell line, (iii) their potential to induce CYP450 activity, and (iv) the role of CYP3A4 in cytotoxicity induced by lipophilic phycotoxins. Our results indicate that while OA, DTX-1 and DTX-2 activated PXR-dependent transcriptional activity in HepG2 cells, no increase of CYP450 (1A2, 3A4, 2C9, 2C19) activities were observed in HepaRG cell following a 72h treatment with these toxins. Multiparametric analysis showed that OA, DTX-1, DTX-2, and PTX-2 were highly cytotoxic in HepaRG cells; inducing cell loss, activation of caspase-3 and γ-H2AX formation. However, no toxicity was observed for YTX, SPX, and AZAs. Moreover, we found that inhibition of CYP3A4 activity by ketoconazole enhances the toxic effects of OA, DTX-1, DTX-2, and PTX-2 in HepaRG cells. Taken together, these results suggest that CYP3A4-mediated metabolism of some lipophilic phycotoxins decreases their in vitro toxicity.

Polymorphism of the CYP2D6 gene in women with breast cancer treated with tamoxifen.

OBJECTIVE: To evaluate polymorphism frequency of the CYP2D6*4, *10, and * 17 alleles in women with breast cancer treated with tamoxifen. MATERIALS AND METHODS: Ninety-five women with estrogen and progesterone receptor-positive breast carcinoma were investigated from September to December 2013. A three-ml sample of peripheral blood was collected from each patient to analyze the presence of CYP2D6 *4, *10, and *17 allele polymorphism by specific polymerase chain reaction technique (PCR) for analysis of haplotypes *1, *4, *10, and *17, determined by studies of different single-nucleotide polymorphism (SNP). The data obtained were compiled and analyzed with the aid of Excel software 2010. RESULTS: The frequency of CYP2D6 alleles *4, *10, and *17 was 16%, 29%, and 2%, respectively, and haplotype * 1/*10 was shown in 22% of the women. The phenotype of intermediate metabolism occurred in 8% of women. CONCLUSIONS: The present study showed a deficiency in tamoxifen metabolism, characterized by intermediate metabolism in 8% of Brazilian women.

DAX1 Overexpression in Pediatric Adrenocortical Tumors: A Synergic Role with SF1 in Tumorigenesis.

DAX1 transcription factor is a key determinant of adrenogonadal development, acting as a repressor of SF1 targets in steroidogenesis. It was recently demonstrated that DAX1 regulates pluripotency and differentiation in murine embryonic stem cells. In this study, we investigated DAX1 expression in adrenocortical tumors (ACTs) and correlated it with SF1 expression and clinical parameters. DAX1 and SF1 protein expression were assessed in 104 ACTs from 34 children (25 clinically benign and 9 malignant) and 70 adults (40 adenomas and 30 carcinomas). DAX1 gene expression was studied in 49 ACTs by quantitative real-time PCR. A strong DAX1 protein expression was demonstrated in 74% (25 out of 34) and 24% (17 out of 70) of pediatric and adult ACTs, respectively (χ(2)=10.1, p=0.002). In the pediatric group, ACTs with a strong DAX1 expression were diagnosed at earlier ages than ACTs with weak expression [median 1.2 (range, 0.5-4.5) vs. 2.2 (0.9-9.4), p=0.038]. DAX1 expression was not associated with functional status in ACTs. Interestingly, a positive correlation was observed between DAX1 and SF1 protein expression in both pediatric and adult ACTs (r=0.55 for each group separately; p<0.0001). In addition, DAX1 gene expression was significantly correlated with SF1 gene expression (p<0.0001, r=0.54). In conclusion, DAX1 strong protein expression was more frequent in pediatric than in adult ACTs. Additionally, DAX1 and SF1 expression positively correlated in ACTs, suggesting that these transcription factors might cooperate in adrenocortical tumorigenesis.

In vitro human metabolism of permethrin isomers alone or as a mixture and the formation of the major metabolites in cryopreserved primary hepatocytes.

In vitro metabolism of permethrin, a pyrethroid insecticide, was assessed in primary human hepatocytes. In vitro kinetic experiments were performed to estimate the Michaelis-Menten parameters and the clearances or formation rates of the permethrin isomers (cis- and trans-) and three metabolites, cis- and trans-3-(2,2 dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis- and trans-DCCA) and 3-phenoxybenzoic acid (3-PBA). Non-specific binding and the activity of the enzymes involved in permethrin's metabolism (cytochromes P450 and carboxylesterases) were quantified. Trans-permethrin was cleared more rapidly than cis-permethrin with a 2.6-factor (25.7±0.6 and 10.1±0.3 µL/min/10(6) cells respectively). A 3-factor was observed between the formation rates of DCCA and 3-PBA obtained from trans- and cis-permethrin. For both isomers, the rate of formation of DCCA was higher than the one of 3-PBA. The metabolism of the isomers in mixture was also quantified. The co-incubation of isomers at different ratios showed the low inhibitory potential of cis- and trans-permethrin on each other. The estimates of the clearances and the formation rates in the co-incubation condition did not differ from the estimates obtained with a separate incubation. These metabolic parameters may be integrated in physiologically based pharmacokinetic (PBPK) models to predict the fate of permethrin and metabolites in the human body.

Ki-67 antigen expression in the mammary epithelium of female rats in persistent estrus treated with raloxifene.

OBJECTIVE: To evaluate Ki-67 antigen expression in the mammary epithelium of female rats in persistent estrus treated with raloxifene. MATERIALS AND METHODS: Forty-one Wistar-Hannover rats in persistent estrus induced by 1.25 mg of testosterone propionate were randomly divided into two groups: Group A (control, n = 21) in which the animals received only the vehicle (propylene glycol) and Group B (experimental, n = 20) in which the rats received 750 µg/day of raloxifene by gavage. After 21 days of treatment, all the animals were sacrificed and the first pair of abdominal-inguinal mammary glands was extirpated and fixed in 10% buffered formalin to investigate Ki-67 expression by immunohistochemistry. The data were analysed using Student's t-test (p < 0.05). RESULTS: The percentage of Ki-67-stained nuclei per 500 cells in the mammary epithelium was 42.33 ± 6.18 and 15.51 ± 3.71 [mean ± standard error of the mean (SEM)] in the control and experimental groups, respectively (p < 0.001). CONCLUSION: Raloxifene treatment significantly reduced Ki-67 expression in the mammary epithelium of rats in persistent estrus.

The PERICLES research program: an integrated approach to characterize the combined effects of mixtures of pesticide residues to which the French population is exposed.

Due to the broad spectrum of pesticide usages, consumers are exposed to mixtures of residues, which may have combined effects on human health. The PERICLES research program aims to test the potential combined effects of pesticide mixtures, which are likely to occur through dietary exposure. The co-exposure of the French general population to 79 pesticide residues present in the diet was first assessed. A Bayesian nonparametric model was then applied to define the main mixtures to which the French general population is simultaneously and most heavily exposed. Seven mixtures made of two to six pesticides were identified from the exposure assessment. An in vitro approach was used for investigating the toxicological effects of these mixtures and their corresponding individual compounds, using a panel of cellular models, i.e. primary rat and human hepatocytes, liver, intestine, kidney, colon and brain human cell lines. A set of cell functions and corresponding end-points were monitored such as cytotoxicity, real-time cell impedance, genotoxicity, oxidative stress, apoptosis and PXR nuclear receptor transactivation. The mixtures were tested in equimolar concentrations. Among the seven mixtures, two appeared highly cytotoxic, five activated PXR and depending on the assay one or two were genotoxic. In some experiments, the mixture effect was quantitatively different from the effect expected from the addition concept. The PERICLES program shows that, for the most pesticides mixtures to which the French general population is exposed, the toxic effects observed on human cells cannot be easily predicted based on the toxic potential of each compound. Consequently, additional studies should be carried on in order to more accurately define the mixtures of chemicals to which the consumers are exposed, as well as to improve the investigation, prediction and monitoring of their potential human health effects.

Performance evaluation of a new fourth-generation HIV combination antigen-antibody assay.

Education and diagnostic tests capable of early detection represent our most effective means of preventing transmission of human immunodeficiency virus (HIV). The importance of early detection is underlined by studies demonstrating increased life expectancy following early initiation of antiviral treatment. The Elecsys(®) HIV combi PT assay is a fourth-generation antigen-antibody combination assay developed to allow earlier detection of seroconversion, and to have increased sensitivity and improved specificity. We aimed to determine how early the assay could detect infection compared with existing assays; whether all HIV variants could be detected; and the assay's specificity using samples from blood donors, routine specimens, and patients with potential cross-reacting factors. Samples were identified as positive by the Elecsys(®) assay 4.9 days after a positive polymerase chain reaction result (as determined by the panel supplier), which was earlier than the 5.3-7.1 days observed with comparators. The analytical sensitivity of the Elecsys(®) HIV combi PT assay for the HIV-1 p24 antigen was 1.05 IU/mL, which compares favorably with the comparator assays. In addition, the Elecsys(®) assay identified all screened HIV subtypes and displayed greater sensitivity to HIV-2 homologous antigen and antibodies to HIV-1 E and O and HIV-2 than the other assays. Overall, the specificity of the Elecsys(®) assay was 99.88 % using samples from blood donors and 99.81 % when analyzing unselected samples. Potential cross-reacting factors did not interfere with assay performance. The Elecsys(®) HIV combi PT assay is a sensitive and specific assay that has been granted the CE mark according to Directive 2009/886/EC.

Diagnostics and management of sleep-related respiratory disturbances in children with skeletal dysplasia caused by FGFR3 mutations (achondroplasia and hypochondroplasia).

To evaluate the frequency of clinical indicators for sleep-related respiratory disturbances (SRD) and the polysomnographical manifestations of these disorders in children with skeletal dysplasia caused by FGFR3 mutations. From January 1990 to January 2009, 24 patients (22 achondroplasia, 2 hypochondroplasia; 13 boys, 11 girls; age 8 days to 15 years, median age 3.0 years) were examined, including a semi-structured interview, a clinical examination, and a polysomnographic sleep recording (65 polysomnographic sleep recordings (PSG) in 24 patients). We performed PSG in a subgroup of five patients before and after adenoidectomy (AT) and/or tonsilectomy (TE). Daytime symptoms suggestive of SRD (daytime somnolence, attention and concentration problems, behavioural problems, and pallor) were found in 4/24 patients (16.7%). Sleep-related symptoms (snoring, mouth breathing, cyanosis, observed apneas, excessive sweating, enuresis, problems of initiating and maintaining sleep) were present in 18/24 patients (75%). Prior to the first PSG, 11/24 patients (45.8%) had undergone AT, 1/24 (4.2%) TE, 2/24 (8.3%) adenotonsilectomy (ATE), 3/24 (12.5%) liquor drainage, and 6/24 (25%) a craniocervical decompression operation. Clinical examination prior to PSG revealed hypertrophied tonsils in 11/24 patients (45.8%), disturbed nasal breathing in 8/24 patients (33.3), and enlarged cervical lymph nodes as a sign of chronic tonsillitis in 5/24 patients (20.8%). PSG findings were abnormal in 19/24 patients (79.2%) with a nadir of oxygen saturation (pulse oximetry) below 90% and/or a nadir of transcutaneous partial pressure of oxygen below 45 mmHg. Pathologic PSG findings were found in 10/24 patients (41.7%): obstructive sleep apnea syndrome (OSAS) was diagnosed in 8/24 patients (33.3%), central sleep apnea syndrome in 1/24 patients (4.2%), and hypoventilation in 1/24 patients (4.2%). As a consequence, the following therapeutic interventions were performed: AT in 1/24 patients (4.2%), TE in 2/24 (8.3%), ATE in 2/24 (8.3%), and nasal continuous positive airway pressure (continuous positive airway pressure) and bilevel positive airway pressure therapy (bilevel positive airway pressure), respectively, in 3/24 patients(12.5%). SRD, especially OSAS, represent a complication of clinical and prognostic relevance in children with achondroplasia. We therefore think that not only those children with a history suggestive of SRD, but all achondroplastic children should be evaluated by PSG. At least in a part of these patients, the pathophysiological mechanisms of OSAS are connected with the etiology of achondroplasia. Achondroplastic children with OSAS, who do not benefit from AT and/or TE, should be treated with NCPAP therapy.

High prevalence of ST121 in community-associated methicillin-susceptible Staphylococcus aureus lineages responsible for skin and soft tissue infections in Portuguese children.

In order to evaluate the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Portugal, we analyzed a collection of 38 S. aureus isolates recovered from 30 children attending the pediatric emergency department of a central hospital in Lisbon due to skin and soft tissue infections. Molecular characterization identified seven clonal lineages among the 35 methicillin-susceptible S. aureus (MSSA) isolates, of which the major lineage PFGE A/t159/ST121 included 63% of the isolates. The three MRSA isolates belonged to the Pediatric clone PFGE D/t535/ST5-IV (n = 2) and to the European CA-MRSA clone PFGE G/t044/ST80-IVc (n = 1). All isolates harbored several virulence factors, namely, leukocidins. Panton-Valentine leukocidin (PVL) was produced by isolates from five MSSA lineages and by the ST80 MRSA. Of interest, this is the first reported isolation of CA-MRSA ST80 in Portugal.

Análise das forças desenvolvidas durante a obturação do canal radicular por diferentes operadores / Analysis of forces developed during root canal filling by different operators

Introdução: procedimentos endodônticos podem contribuir tanto para o desenvolvimento da fratura radicular vertical como para outros defeitos localizados, como linhas de fissura ou rachaduras incompletas na dentina radicular. O objetivo deste estudo foi avaliar a resistência máxima de fratura radicular e a força produzida por cinco diferentes operadores nas condensações lateral e vertical durante a obturação do canal radicular. Métodos: foram selecionados 74 dentes humanos, caninos superiores(CS) e pré-molares inferiores (PMI). Para determinara resistência máxima de fratura durante a condensação, foram utilizados 24 dentes, submetidos a carregamento axial de compressão até a ocorrência da fratura radicular em uma máquina de ensaios mecânicos. Cinquenta dentes foram utilizados para mensuração da força axial de condensação, por meio de dispositivo desenvolvido para simular condições clínicas de trabalho. Resultados:os valores médios de resistência à fratura em Kgforam: CS=14,96±2,65 e PMI=7,56±1,05. Os valores médios, em Kg, das forças exercidas pelos cinco operadoresforam respectivamente 2,49; 3,75; 2,24; 2,08 e1,18. Nenhum operador atingiu, durante os procedimentos,a força máxima de fratura radicular. Conclusões:diferentes comportamentos entre os cinco profissionais monitorados foram observados para a mesma técnica de obturação. O aumento da força durante a condensação não gerou melhora radiográfica da obturação do canal radicular. Durante a obturação, as condensações lateral e, principalmente, a vertical devem ser realizadas com força e pressão apical reduzidas, evitando tensões excessivas e desnecessárias à dentina radicular

Objectives: Endodontic procedures might contribute tothe development of vertical root fracture as well as otherlocalized defects such as craze lines or incomplete cracksin root dentine. The objective of this study was to evaluatethe maximum fracture resistance and the force producedby five different operators in lateral and verticalcondensation during root canal filling. Methods: 74 humanteeth, superior canines (SC) and inferior premolars(IPM) were selected. In order to determine the maximumfracture resistance during condensation, 24 teeth weresubmitted until failure to an axial compression load in auniversal testing machine. Fifty teeth were used in orderto measure the axial condensation force by means of adevice developed to simulate clinical working conditions.Results: Fracture resistance mean values in kg were: SC= 14.96±2.65 and IPM = 7.56±1.05. Mean values of forceapplied by each of the five operator in Kg were, respectively:2.49; 3.75; 2.24; 2.08 and 1.18. None of the operatorsachieved teeth’s maximum fracture resistance duringprocedures. Conclusions: Different behaviors amongfive professionals monitored were observed for the sametechnique of root canal filling. The increase in strengthduring condensation had no radiographic improvement ofroot canal filling. During the root canal filling, lateral andespecially vertical condensation, must be performed withreduced apical strength and pressure, avoiding excessiveand unnecessary stress to root dentin.

Intravenous immunoglobulin in lupus panniculitis.

Systemic lupus erythematosus (SLE) is a disease of unknown cause that may involve one or many organ or systems. Skin involvement is a major feature in this disease, and a wide variety of skin conditions may be present. Lupus erythematosus panniculitis (LEP) constitutes a rare form of cutaneous lupus characterized by recurrent nodular or plaque lesions that can vary from a benign and mild course to a more disfiguring disease. Initial therapy includes corticosteroids, antimalarials, and azathioprine and, in refractory cases, two antimalarials in association, mycophenolate mofetil, or other immunomodulators. Intravenous immuglobulin (IVIG) is used in many autoimmune disorders, like in SLE, although clinical trials have not yet taken place. In this report, we review skin manifestations of SLE and their treatment, IVIG, and finally a case of LEP successfully treated with IVIG when other therapy modalities failed.

Clotrimazole protects the liver against normothermic ischemia-reperfusion injury in rats.

OBJECTIVE: To investigate the possible antiapoptotic prosurvival role of the pregnane X receptor (PXR) in hepatic ischemia-reperfusion injury in rats using clotrimazole (CTZ), a strong PXR transactivator. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into 3 groups of 6 each: sham-treated, control, and CTZ-treated animals. Control and CTZ-treated animals were subjected to 30 minutes of normothermic ischemia of the whole liver followed by 6 hours of reperfusion. The animals were then killed, and the liver was excised and blood samples collected. RESULTS: Clotrimazole induced a significant increase in expression of the CYP3A gene, indicating PXR transactivation, whereas expression of the antiapoptotic Bcl-xL gene was not increased. Serum concentrations of aspartate aminotransaminase and alanine aminotransaminase were lower in CTZ-treated animals than in control animals (difference not significant). Levels of poly(adenosine diphosphate-ribose) polymerase, a caspase-3 substrate, remained significantly higher in the CTZ-treated group compared with controls (P < .05). Clotrimazole increased the expression of phospho-p 44/42 extracellular signal-regulated kinase 1,2 (P < .05). The gene expression of the heat shock proteins 27, 70 and 90 was significantly lower in CTZ-treated animals than in controls (P < .05). CONCLUSION: Clotrimazole-mediated PXR transactivation protects the liver against ischemia-reperfusion apoptosis in rats. Phospho-p 44/42 extracellular signal-regulated kinase 1,2 is activated, whereas gene expression of heat shock proteins 27, 70, and 90 is downregulated by induction of PXR.

Hemodynamic responses to exercise in obese children and adolescents before and after overweight reduction.

OBJECTIVE: To determine the change of hemodynamic parameters in graded bicycle exercise testing in obese children before and after overweight reduction. METHODS: Forty-two obese children (mean age 11 years) and 40 healthy, lean children underwent graded bicycle exercise testing (1, 1.5, 2, 2.5 Watt/kg) recording the heart rate (HR) and blood pressure (BP) before exercise (T1), at maximum load (T2), and 6 min after ending the exercise (T3). Furthermore, the increase of the patient's heart rate within each ramp (I-HR) and the individual maximum load (Watt/kg) were recorded. After participating in an one-year outpatient intervention program for obese children, the study group underwent exercise testing again. Furthermore, we analyzed the lipid and insulin levels in the study group before and after overweight reduction and correlated the changes of the hemodynamic parameters to the changes of the insulin and lipid levels. RESULTS: The obese children had significantly (p<0.05) higher systolic blood pressure values at T1, T2, and T3 as compared to the lean children. The I-HR was significantly (p<0.05) higher in the study group. HR and BP at T1, T2, and T3, and the lipid and insulin values improved significantly in the study group after overweight reduction. The changes of HR and BP did not correlate to the changes of insulin and lipids. CONCLUSION: Compared to lean children, obese children demonstrated a significantly lower exercise capacity of the cardiovascular system, which improved after participating in an obesity intervention program. Overweight reduction influences the hemodynamic and metabolic changes of childhood obesity positively and thereby leads to an improvement of the cardiovascular risk factor profile.

Peritoneal implantation of cryopreserved encapsulated porcine hepatocytes in rats without immunosuppression: viability and function.

The bioartificial liver (BAL) represents a promising approach to cell transplantation without immunosuppression as a method to support patients with hepatic insufficiency. The aim of this study was to assess viability and function of cryopreserved encapsulated porcine hepatocytes implanted intraperitoneally in rats without immunosuppression. Isolated porcine hepatocytes were cryopreserved at -196 degrees C for 1 month. Four groups were created: group 1 (n=10), freshly encapsulated porcine hepatocytes cultured in albumin-free medium for 10 days; group 2 (n=10), freshly encapsulated porcine hepatocytes implanted in the rat peritoneum without immunosuppression for 1 month and cultured for 10 days after explantation; group 3 (n=10), cryopreserved encapsulated porcine hepatocytes cultured for 10 days; group 4 (n=10), cryopreserved encapsulated porcine hepatocytes implanted in the rat peritoneum without immunosuppression for 1 month and cultured for 10 days after explantation. We assessed urea and albumin production and hepatocyte viability. The hepatocytes of all groups retained the capacity to produce urea and albumin, although the albumin synthesis was significantly decreased among hepatocytes of group 4 (P< .01). Encapsulated cryopreserved porcine hepatocytes explanted from rat peritoneum after 1 month appeared morphologically viable; their ultrastructure was preserved. In conclusion, long-term cryopreservation of porcine hepatocytes resulted in retention of their biological activity and in significant viability when transplanted into the rat peritoneum without immunosuppression.

Four-year follow-up of children and adolescents participating in an obesity intervention program.

BACKGROUND: Since obesity affects children's health and social integration, treatment concepts with long-term efficiency are necessary. METHODS: We analyzed changes of standard deviation score of body mass index (SDS-BMI) quarterly in the first year and once a year during the next 3 years in all obese children participating in the 1-year outpatient intervention program 'Obeldicks', which was based on physical exercise, nutrition education and behavior therapy. All analyses were performed on the intention-to-treat approach. RESULTS: One hundred and thirty-one children (77%) of the 170 children (mean age 10.5 years, 51% female, mean BMI 26.9 kg/m(2), mean SDS-BMI 2.54) attending the 'Obeldicks' intervention program reduced their overweight at the end of intervention (mean SDS-BMI reduction 0.41) and 122 (66%) 3 years after end of intervention (mean SDS-BMI reduction 0.48). The reduction of overweight was independent of the child's gender, age and parental age and BMI. Reduction of 0.33 SDS-BMI in the first 3 months was the best predictor for long-term success (95% predictive value). CONCLUSIONS: Participating in the 1-year outpatient obesity intervention program 'Obeldicks' was associated with a decrease of overweight, which was sustained 3 years after the end of intervention. Reduction of overweight in the first 3 months of the intervention was highly predictive for long-term success.