Nutritional risk among Brazilian children 2 to 6 years old: A multicenter study

ObjectiveTo estimate the nutritional risk in children 2 to 6 y old.MethodsThe sample consisted of 3058 children enrolled in public and private schools in nine Brazilian cities. The assessment of nutrient intake was based on 1-d data combining direct individual weighing of foods and a food diary. A second evaluation of food consumption was conducted in a subsample to estimate the usual intake.ResultsThere was low prevalence of inadequate intake of vitamin B6 (<0.001%), riboflavin (<0.001%), niacin (<0.001%), thiamin (<0.001%), folate (<0.001%), phosphorus (<0.1%), magnesium (<0.1%), iron (<0.5%), copper (<0.001%), zinc (<0.5%), and selenium (<0.001%). However, 22% of children younger than 4 y and 5% of children older than 4 y consumed fiber quantities larger than the adequate intake. Approximately 30% of the sample consumed more saturated fat than recommended. The prevalence of inadequate vitamin E intake ranged from 15% to 29%. More than 90% of the children had an inadequate vitamin D intake. In children older than 4 y, the prevalence of inadequate calcium intake was approximately 45%. Sodium intake was higher than the upper intake level in 90% of children younger than 4 y and 73% of children older than 4 y.ConclusionsThe prevalence of inadequate dietary intake was low for most nutrients. However, fiber, calcium, and vitamin D and E intakes were lower than recommended. Moreover, children consumed large amounts of sodium and saturated fat.     

Trends in social and demographic inequalities in the prevalence of chronic diseases in Brazil. PNAD: 2003- 2008

The aims of this study are: to evaluate the prevalence of chronic diseases in the Brazilian population comparing data of 2008 with those of 2003; to estimate the impact of chronic conditions on the use of health services and on the restriction of daily activities and to measure the differentials in the prevalence of specific diseases according to educational strata and the affiliation to a private health plan. Data were obtained from PNAD 2008 and 2003. The analysis included estimations of crude and adjusted prevalence ratios, using svy commands from Stata 11 software. The prevalence of at least one disease was higher in: the elderly, women, low schooling level, black or indigenous people, urban residents, migrants and people living in the south region of Brazil. The most frequent diseases were: hypertension, back and spinal cord disorders, arthritis and depression. Between 2003 and 2008, an increase in the prevalence of diabetes, hypertension, cancer and cirrhosis was observed, and there was a reduction in chronic kidney failure and tuberculosis. All the diseases analyzed, with the exception of cancer and tendinitis/tenossinovitis, revealed a higher prevalence in low educational level strata. The greatest social inequalities were in chronic kidney failure, cirrhosis, tuberculosis and arthritis/rheumatism.     

Group for the re-education of eating habits: a holistic experience in health from the family perspective

This study describes the experience of the development of a family educational program to develop healthier eating habits. The program can enable the population to evaluate its quality of life. It can be justified if we consider obesity as a risk factor for the aging population in Brazil and the unpreparedness of the health system and society regarding this subject. The present work, which lasted two months, was carried out in a micro-area of the municipal district of Ribeir?o Preto with groups of around 13 people. Most of the participants were women who cooperated with the making of healthier menus. In order to give continuity to the process, maintenance groups were created. This program can contribute to self-care and self-commitment, giving support to healthier life styles.     

Cerebral Blood Flow and Metabolism in the Wernicke-Korsakoff Syndrome

Cerebral blood flow and metabolism were measured by the iodoantipyrine-4-¹³¹I method in nine patients and by the nitrous oxide method in three patients with the Wernicke-Korsakoff syndrome.     

GSTP1 and ABCB1 Polymorphisms Predicting Toxicities and Clinical Management on Carboplatin and Paclitaxel‐Based Chemotherapy in Ovarian Cancer

Variation in drug disposition genes might contribute to susceptibility to toxicities and interindividual differences in clinical management on chemotherapy for epithelial ovarian cancer (EOC). This study was designed to explore the association of GST and ABCB1 genetic variation with hematologic and neurologic toxicity, changes in chemotherapy, and disease prognosis in Brazilian women with EOC. A total of 112 women with a confirmed histological diagnosis of EOC treated with carboplatin/paclitaxel were enrolled (2014–2019). The samples were analyzed by multiplex polymerase chain reaction (PCR) for the deletion of GSTM1 and GSTT1 genes. GSTP1 (c.313A>G/rs1695) and ABCB1 (c.1236C>T/rs1128503; c.3435C>T/rs1045642; c.2677G>T>A/rs2032582) single nucleotide polymorphisms (SNPs) were detected by real‐time PCR. Subjects with the GSTP1 c.313A>G had reduced risk of anemia (odds ratio (OR): 0.17, 95% confidence interval (CI): 0.04–0.69, P = 0.01, dominant model) and for thrombocytopenia (OR: 0.27, 95% CI: 0.12–0.64, P < 0.01; OR 0.18, 95% CI 0.03–0.85, P = 0.03, either dominant or recessive model), respectively. The GSTP1 c.313A>G AG genotype was associated with a lower risk of dose delay (OR: 0.35, 95% CI: 0.13–0.90, P = 0.03). The ABCB1 c.1236C>T was associated with increased risk of thrombocytopenia (OR: 0.15, 95% CI: 0.03–0.82, P = 0.03), whereas ABCB1 c.3435C>T had increased risk of grade 2 and 3 neurotoxicity (OR: 3.61, 95% CI: 1.08–121.01, P = 0.03) in recessive model (CC + CT vs. TT). This study suggests that GSTP1 c.313A>G, ABCB1 c.1236C>T, and c.3435C>T SNP detection is a potential predictor of hematological toxicity and neurotoxicity and could help predict the clinical management of women with EOC.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Variation in drug disposition genes encoding drug‐metabolizing enzymes and transporters might contribute to susceptibility to toxicities and interindividual differences in clinical management such as the need to delay, reduce, or discontinue treatment.

• WHAT QUESTION DID THIS STUDY ADDRESS?

We studied the association of GST and ABCB1 genetic variation with hematologic and neurologic toxicity, clinical management, and disease prognosis in Brazilian women with epithelial ovarian carcinoma (EOC) who undergo carboplatin and paclitaxel‐based chemotherapy.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

GSTP1 c.313A>G is a potential predictor of anemia and thrombocytopenia and associated with a lower risk of dose delay during chemotherapy. In addition, ABCB1 c.1236C>T and c.3435C>T is associated with a higher risk of thrombocytopenia and neurotoxicity.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

The polymorphism detection could be a strategy to careful monitoring of patients at increased risk of toxicity and appropriate supportive therapy could decrease the need for changes in treatment, thus improving the likelihood of a beneficial treatment response in women with EOC.

Epithelial ovarian cancer (EOC) is the most common cause of gynecological cancer death, largely due to the advanced stage of the disease at the time of diagnosis. ¹ Standard first‐line treatment is cytoreductive surgery and subsequent chemotherapy using a combination of carboplatin and paclitaxel or neoadjuvant chemotherapy and residual tumor resection. ² Despite a high response rate to chemotherapy, ~ 70% of the women have a relapse within the subsequent 3 years. ³ Platinum and taxane‐based chemotherapy are often associated with severe hematological toxicities, such as anemia, neutropenia, leukopenia, and thrombocytopenia. ⁴ In addition, neuropathy is a dose‐limiting side effect of paclitaxel. ⁵ , ⁶ Interindividual differences in carboplatin and paclitaxel toxicity may be associated with polymorphisms in genes encoding drug‐metabolizing enzymes and transporters, including GSTs and ATP‐binding cassette (ABC) efflux transporters like ABCB1. ⁴ , ⁷ , ⁸ , ⁹ The GSTs are a family of phase II enzymes involved in detoxification of xenobiotics by conjugation reactions between glutathione and endogenous and exogenous electrophilic compounds, such as chemotherapeutic drugs, including the platinum agents. The GST family consists of several gene subfamilies of which GSTM1, GSTT1, and GSTP1 are the most relevant for drug metabolism. ¹⁰ , ¹¹ Functional GSTM1 and GSTT1 enzymes are directly related with the presence of the intact genes, because the absence of activity is the result of a 15 kb and 54 kb deletions that span the entire GSTM1 and GSTT1 genes (GSTM1‐null and GSTT1‐null genotypes), respectively. Consequently, individuals homozygous for the GSTM1 or GSTT1‐null allele have a complete absence of GSTM1 and GSTT1 activity, whereas individuals with two copies of the GSTM1 or GSTT1 genes have reference protein levels. ¹² , ¹³ There is some evidence that these deletion genotypes may play a role in toxicity, response to treatment, and survival in some cancers, ¹⁴ , ¹⁵ , ¹⁶ including cancer of the ovary. ⁸ In contrast to the commonly studied GSTM1 and GSTT1 genotypes, the GSTP1 c.313A>G (rs1695) is an exonic single nucleotide polymorphism (SNP) that causes an amino acid substitution and results in an isoleucine to valine (Ile > Val) change at codon 105 of the enzyme. The highest level of GSTP1 activity is seen in individuals with the AA genotype (Ile/Ile) and is associated with increased toxicity in different carcinomas, but there are discordant results regarding the effect of GSTP1 c.313A>G on treatment outcomes. ⁹ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ Polymorphisms in ABCB1 or multidrug resistance 1 may affect the function of P‐glycoprotein, a critical transporter for efflux of paclitaxel from cells. ²¹ , ²² Three SNPs in the coding region of ABCB1 (c.1236C>T, rs1128503; c.3435C>T, rs1045642; and c.2677G>T>A, rs2032582) have been extensively studied. ²³ , ²⁴ These common ABCB1 SNPs have been associated with toxicity during carboplatin and paclitaxel‐based chemotherapy, including increased risk of anemia in carriers of the c.1236C>T SNP, a more pronounced neutrophil decrease in patients carrying the c.3435C>T and c.2677G>T>A SNPs and increased risk of peripheral neuropathy associated with the c.3435C>T SNP. ¹⁸ , ²⁵ , ²⁶ Similar to studies of GST polymorphisms, the associations of ABCB1 genetic variation with treatment outcomes is inconsistent across studies. ²⁷ , ²⁸ Patients developing severe toxicities often require dose reduction, dose delay, or treatment interruption that require clinical interventions and may affect the disease prognosis. ⁴ However, no study has been found so far focus on regarding the utility of polymorphisms in the management of chemotherapy and toxicities for ovarian cancer. The current study was designed to examine the association of GST and ABCB1 genetic variants with hematologic and neurologic toxicities, clinical management on chemotherapy, and disease prognosis in Brazilian women with EOC.     

cDNA microarray analysis of differentially expressed genes in penile tissue after treatment with tadalafil

OBJECTIVE

To evaluate differential gene expression in penile tissue after treatment with the phosphodiesterase 5 (PDE5) inhibitor tadalafil, as of the three clinically available PDE5 inhibitors (sildenafil, tadalafil, and vardenafil) used for the treatment of erectile dysfunction (ED), tadalafil has a long half‐life and low incidence of side‐effects.

MATERIALS AND METHODS

In all, 32 adult rats were divided into two groups. The control group received 0.5 mL of drinking water alone, while the tadalafil group was treated with tadalafil at a dose of 0.27 mg/kg. At 4 h after treatment with water or tadalafil the rats were killed and the penile tissue was removed. The total RNA was isolated from the penile tissue from both groups and differentially expressed genes were identified by cDNA microarray analysis. To validate the expression data from the microarray analysis, quantitative real‐time polymerase chain reaction (PCR) and immunohistochemistry were used.

RESULTS

In all, 153 genes were differentially expressed between the control group and the tadalafil group. We validated the microarray results by quantitative PCR for the insulin‐like growth factor binding protein 6 (IGFBP‐6) gene and the neuronal calcium sensor 1 (NCS‐1) gene, both of which were up‐regulated in the tadalafil group, and for the natriuretic peptide receptor 1 (NPR‐1) gene that was down‐regulated in this group. Immunohistochemistry showed localization of the NCS‐1 protein in sinusoid trabeculae of the corpus cavernosum in control and tadalafil‐treated rats.

CONCLUSIONS

There was differential expression in 153 genes after tadalafil treatment. Some of these genes such as IGFBP‐6, NPR‐1 and NCS‐1, might result in new targets in the treatment of ED.