Associations between Urinary and Dietary Selenium and Blood Metabolic Parameters in a Healthy Northern Italy Population.

Selenium is both an essential nutrient and a highly toxic element, depending on its dose and chemical forms. We aimed to quantify urinary selenium excretion and dietary selenium intake in 137 healthy non-smoking blood donors living in the northern Italian province of Reggio Emilia. We assessed selenium status by determining urinary selenium levels (mean 26.77 µg/L), and by estimating dietary selenium intake (mean 84.09 µg/day) using a validated semi-quantitative food frequency questionnaire. Fasting blood levels of glucose, lipids and thyroid-stimulating hormone were measured using automatized laboratory procedures. Dietary and urinary selenium were correlated (beta coefficient (ß) = 0.19). Despite this, the association of the two indicators with health endpoints tended to diverge. Using linear regression analysis adjusted for age, sex, body mass index, cotinine levels and alcohol intake, we observed a positive association between urinary selenium and blood triglyceride (ß = 0.14), LDL-cholesterol (ß = 0.07) and glucose levels (ß = 0.08), and an inverse one with HDL-cholesterol (ß = -0.12). Concerning dietary selenium, a slightly positive association could be found with glycemic levels only (ß = 0.02), while a negative one emerged for other endpoints. The two selenium indicators showed conflicting and statistically highly imprecise associations with circulating TSH levels. Our findings suggest that higher selenium exposure is adversely associated with blood glucose levels and lipid profile. This is the case even at selenium exposures not exceeding tolerable upper intake levels according to current guidelines.

Comparison of Methodologies to Estimate Dietary Cadmium Intake in an Italian Population.

Cadmium is a metal that is toxic to humans, and the major source of cadmium exposure in the non-smoking general population is diet. To identify major food sources and lower exposure from diet, an accurate estimate of dietary cadmium intake is needed. Hence, the objectives of this study are to develop a method to assess dietary cadmium intake using a biomarker measurement and to improve the estimation of dietary cadmium intake when using a food frequency questionnaire (FFQ). In a random sample of an Italian population, we collected dietary habits by FFQ and measured cadmium in foods and beverages. These data were used to compute the estimated weekly dietary intake (WDI) of cadmium (µg) by kilogram (kg) of body weight (bw) (WDIFFQ). We also measured fasting serum cadmium levels by inductively-coupled plasma mass spectrometry. We used these data to develop a model for the estimation of the biomarker-derived dietary cadmium intake (WDIbio). In the 51 subjects recruited, the median level of serum cadmium was 0.041 µg/L (interquartile range (IQR): 0.030-0.054). The median WDIFFQ and WDIbio were 1.34 µg/kg bw/week (IQR: 0.86-1.70) and 0.72 µg/kg bw/week (IQR: 0.55-1.11), respectively. The correlation between the two estimates was low-to-moderate (r = 0.291). In exploratory analyses, the correlation was slightly higher in women and participants ages <50 years, and markedly higher in participants with body mass index <25 kg/m2 and smokers. Our approach allows for the dietary contribution to be isolated from the overall cadmium exposure measured with a biomarker; the estimated dietary cadmium intake was roughly similar to that estimated using the FFQ, especially in select subgroups. Future refinements to the biomarker-derived dietary cadmium intake approach should take into consideration additional sources of cadmium exposure, as well as factors affecting its absorption and metabolism.

Perineal Trauma in a Low-risk Maternity with High Prevalence of Upright Position during the Second Stage of Labor.

OBJECTIVE: Perineal trauma is a negative outcome during labor, and until now it is unclear if the maternal position during the second stage of labor may influence the risk of acquiring severe perineal trauma. We have aimed to determine the prevalence of perineal trauma and its risk factors in a low-risk maternity with a high incidence of upright position during the second stage of labor. METHODS: A retrospective cohort study of 264 singleton pregnancies during labor was performed at a low-risk pregnancy maternity during a 6-month period. Perineal trauma was classified according to the Royal College of Obstetricians and Gynecologists (RCOG), and perineal integrity was divided into three categories: no tears; first/second-degree tears + episiotomy; and third and fourth-degree tears. A multinomial analysis was performed to search for associated factors of perineal trauma. RESULTS: From a total of 264 women, there were 2 cases (0.75%) of severe perineal trauma, which occurred in nulliparous women younger than 25 years old. Approximately 46% (121) of the women had no tears, and 7.95% (21) performed mediolateral episiotomies. Perineal trauma was not associated with maternal position (p = 0.285), health professional (obstetricians or midwives; p = 0.231), newborns with 4 kilos or more (p = 0.672), and labor analgesia (p = 0.319). The multinomial analysis showed that white and nulliparous presented, respectively, 3.90 and 2.90 times more risk of presenting perineal tears. CONCLUSION: The incidence of severe perineal trauma was low. The prevalence of upright position during the second stage of labor was 42%. White and nulliparous women were more prone to develop perineal tears.

OBJETIVO: O trauma perineal é um desfecho negativo durante o parto, e é incerto, até o momento, se a posição maternal durante o período expulsivo pode influenciar o risco de evoluir com trauma perineal severo. Nós objetivamos determinar a prevalência de trauma perineal e seus fatores de risco em uma maternidade de baixo risco com alta prevalência de posição vertical durante o período expulsivo. MéTODOS: Um estudo de coorte retrospectivo de 264 gestações únicas durante o trabalho de parto foi realizado durante 6 meses consecutivos. O trauma perineal foi classificado de acordo com o Royal College of Obstetricianns and Gynecologists (RCOG). A integridade perineal foi dividida em três categorias: períneo íntegro; trauma perineal leve (primeiro e segundo graus + episiotomia); e trauma perineal severo (terceiro e quarto graus). Uma análise multinomial foi realizada para buscar variáveis associadas ao trauma perineal. RESULTADOS: De um total de 264 mulheres, houve 2 casos (0,75%)de trauma perineal severo m nulíparas com menos de 25 anos. Aproximadamente 46% (121) das mulheres não tiveram trauma perineal e 7,95% (21) realizaram episiotomias mediolaterais. Não houve correlação do trauma perineal com a posição de parto (p = 0,285), tipo de profissional que realizou o parto (p = 0,231), recém-nascidos com 4.000 gramas ou mais (p = 0,672), e presença de analgesia de parto (p = 0,319). Uma análise multinomial evidenciou que mulheres brancas e nulíparas apresentaram, respectivamente, um risco 3,90 e 2,90 vezes maior de apresentar trauma perineal. CONCLUSãO: A incidência de trauma perineal severo foi baixa. A prevalência de parto vertical durante o período expulsivo foi de 42%. Mulheres brancas e nulíparas foram mais suscetíveis a apresentar trauma perineal.

Perineal trauma in a low-risk maternity with high prevalence of upright position during the second stage of labor / Trauma perineal em uma maternidade de baixo risco com alta prevalência de parto vertical durante o período expulsivo

Abstract Objective Perineal trauma is a negative outcome during labor, and until now it is unclear if the maternal position during the second stage of labormay influence the risk of acquiring severe perineal trauma. We have aimed to determine the prevalence of perineal trauma and its risk factors in a low-risk maternity with a high incidence of upright position during the second stage of labor. Methods A retrospective cohort study of 264 singleton pregnancies during labor was performed at a low-risk pregnancymaternity during a 6-month period. Perineal trauma was classified according to the Royal College of Obstetricians and Gynecologists (RCOG), and perineal integrity was divided into three categories: no tears; first/ second-degree tears + episiotomy; and third and fourth-degree tears. A multinomial analysis was performed to search for associated factors of perineal trauma. Results From a total of 264 women, there were 2 cases (0.75%) of severe perineal trauma, which occurred in nulliparous women younger than 25 years old. Approximately 46% (121) of the women had no tears, and 7.95% (21) performed mediolateral episiotomies. Perineal trauma was not associated with maternal position (p = 0.285), health professional (obstetricians or midwives; p = 0.231), newborns with 4 kilos or more (p = 0.672), and labor analgesia (p = 0.319). The multinomial analysis showed that white and nulliparous presented, respectively, 3.90 and 2.90 times more risk of presenting perineal tears. Conclusion The incidence of severe perineal trauma was low. The prevalence of upright position during the second stage of labor was 42%. White and nulliparous women were more prone to develop perineal tears.

Resumo Objetivo O trauma perineal é um desfecho negativo durante o parto, e é incerto, até omomento, se a posiçãomaternal durante o período expulsivo pode influenciar o risco de evoluir com trauma perineal severo. Nós objetivamos determinar a prevalência de trauma perineal e seus fatores de risco em uma maternidade de baixo risco com alta prevalência de posição vertical durante o período expulsivo. Métodos Um estudo de coorte retrospectivo de 264 gestações únicas durante o trabalho de parto foi realizado durante 6 meses consecutivos. O trauma perineal foi classificado de acordo com o Royal College of Obstetricianns and Gynecologists (RCOG). A integridade perineal foi dividida em três categorias: períneo íntegro; trauma perineal leve (primeiro e segundo graus + episiotomia); e trauma perineal severo (terceiro e quarto graus). Uma análise multinomial foi realizada para buscar variáveis associadas ao trauma perineal. Resultados De um total de 264 mulheres, houve 2 casos (0,75%)de trauma perineal severo m nulíparas com menos de 25 anos. Aproximadamente 46% (121) das mulheres não tiveram trauma perineal e 7,95% (21) realizaram episiotomias mediolaterais. Não houve correlação do trauma perineal com a posição de parto (p = 0,285), tipo de profissional que realizou o parto (p = 0,231), recém-nascidos com 4.000 gramas ou mais (p = 0,672), e presença de analgesia de parto (p = 0,319). Uma análise multinomial evidenciou que mulheres brancas e nulíparas apresentaram, respectivamente, um risco 3,90 e 2,90 vezes maior de apresentar trauma perineal. Conclusão A incidência de trauma perineal severo foi baixa. A prevalência de parto vertical durante o período expulsivo foi de 42%. Mulheres brancas e nulíparas foram mais suscetíveis a apresentar trauma perineal.

Effect of type 2 diabetes mellitus on the pharmacokinetics of metformin in obese pregnant women.

BACKGROUND AND OBJECTIVE: The use of metformin throughout gestation by women with polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) significantly reduces the number of first-trimester spontaneous abortions and the rate of occurrence of gestational diabetes and hypertensive syndromes. Metformin is taken up into renal tubular cells by organic cation transport 2 (OCT2) and eliminated unchanged into the urine. The objective of this study was to analyse the influence of T2DM on the pharmacokinetics of metformin in obese pregnant women and in a control group of non-diabetic obese pregnant women with PCOS. METHODS: Eight non-diabetic obese pregnant women with PCOS and nine obese pregnant women with T2DM taking oral metformin 850 mg every 12 h were evaluated throughout gestation. Serial blood samples were collected over a 12-h period during the third trimester of pregnancy. Steady-state plasma concentrations of metformin were determined by high-performance liquid chromatography with a UV detector. The pharmacokinetic results of the two groups, reported as median and 25th and 75th percentile, were compared statistically using the Mann-Whitney test, with the level of significance set at p < 0.05. RESULTS: The pharmacokinetic parameters detected for PCOS versus T2DM patients, reported as median, were, respectively: elimination half-life 3.75 versus 4.00 h; time to maximum concentration 2.00 versus 3.00 h; maximum concentration 1.42 versus 1.21 µg/mL; mean concentration 0.53 versus 0.56 µg/mL; area under the plasma concentration-time curve from time zero to 12 h 6.42 versus 6.73 µg·h/mL; apparent total oral clearance 105.39 versus 98.38 L/h; apparent volume of distribution after oral administration 550.51 versus 490.98 L; and fluctuation (maximum-minimum concentration variation) of 179.56 versus 181.73 %. No significant differences in pharmacokinetic parameters were observed between the groups. CONCLUSION: T2DM in the presence of insulin use does not influence the pharmacokinetics of metformin in pregnant patients, demonstrating the absence of a need to increase the dose, and consequently does not influence the OCT2-mediated transport in pregnant women with PCOS.

Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome.

BACKGROUND: The use of metformin throughout gestation by pregnant women with polycystic ovary syndrome (PCOS) significantly reduces the number of first trimester spontaneous abortions and the rate of occurrence of gestational diabetes. OBJECTIVE: The objective of this study was to investigate the pharmacokinetics and the placental transfer of metformin in pregnant women with PCOS. PATIENTS AND METHODS: Eight pregnant women with PCOS taking 850 mg metformin every 12 h during the third trimester of pregnancy were evaluated. Maternal blood samples were collected at steady state during the dose interval (0-12 h). Maternal and umbilical cord blood samples were also obtained at delivery. Metformin plasma concentrations were analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using a non-compartmental model. Data are reported as median and minimum and maximum values. RESULTS: Metformin pharmacokinetic parameters were: t(½), 3.8 (2.8-5.4) h; t(max), 2.0 (0.5-3.0) h; C(max), 1.4 (0.5-2.1) mg/L; C(mean), 0.5 (0.2-0.9) mg/L; AUC(0-12), 6.4 (1.1-9.2) mg h/L; Cl/f, 105 (60-274) L/h; Vd/f, 551 (385-1173) L; median fluctuation, 89 (79-95)%. Umbilical/maternal metformin plasma concentration ratios were 0.7 (0.4-1.3). CONCLUSION: Metformin oral clearance (Cl/f) had increased in our patients relative to nonpregnant healthy volunteers or diabetic patients. Therefore, lower plasma metformin concentrations were observed for nondiabetic pregnant women with PCOS. Future studies should be conducted to demonstrate the therapeutic efficacy of metformin during pregnancy. Caution is warranted as umbilical/maternal metformin plasma concentrations ratios of around 0.7 require metformin dosage adjustment.

Influence of gestational diabetes mellitus on the stereoselective kinetic disposition and metabolism of labetalol in hypertensive patients.

PURPOSE: This study investigated the influence of gestational diabetes mellitus on the kinetic disposition and stereoselective metabolism of labetalol administered intravenously or orally. METHODS: Thirty hypertensive women during the last trimester of pregnancy were divided into four groups: non-diabetic and diabetic women treated with intravenous or oral labetalol. RESULTS: The pharmacokinetics of labetalol was not stereoselective in diabetic or non-diabetic pregnant women receiving the drug intravenously. However, oral administration of labetalol resulted in lower values of the area under the plasma concentration versus time curve (AUC) for the ß-blocker (RR) than for the other enantiomers in both diabetic and non-diabetic women. Gestational diabetes mellitus caused changes in the kinetic disposition of the labetalol stereoisomers when administered orally. The AUC values for the less potent adrenoceptor antagonist (SS) and for the α-blocking (SR) isomers were higher in diabetic than in non-diabetic pregnant women. CONCLUSIONS: The approximately 100% higher AUC values obtained for the (SR) isomer in diabetic pregnant women treated with oral labetalol may be of clinical relevance in terms of the α-blocking activity of this isomer.

Stereoselective analysis of labetalol in human plasma by LC-MS/MS: application to pharmacokinetics.

Labetalol is clinically available as a mixture of two racemates (four stereoisomers). The stereoisomer (R,R) has as main activity the beta1-antagonism and the stereoisomer (S,R) is highly selective for the alpha1 adrenoceptor and is responsible for most of the alpha-blocker activity. In the present investigation, a method for the analysis of labetalol stereoisomers in human plasma was developed and applied to pharmacokinetic studies. Plasma samples (0.5 ml) were extracted with methyl tert-butyl ether at pH 9.5. The four labetalol stereoisomers were analyzed by LC-MS/MS on a Chirobiotic V column using a mobile phase consisting of methanol, acetic acid, and diethylamine, with a recovery of more than 90% for all four. The quantitation limit was 0.5 ng/ml and linearity was observed at 250 ng/ml plasma for each stereoisomer. Studies of precision and accuracy presented coefficients of variation and percentage inaccuracy of less than 15%, indicating that the method is precise and accurate. The method was applied to the study of the kinetic disposition of labetalol over a period of 12 h after oral administration of a single 100 mg dose to a hypertensive pregnant woman. The clinical study revealed stereoselectivity in the pharmacokinetics of labetalol, with a lower plasma proportion for the active stereoisomers (R,R)-labetalol and (S,R)-labetalol. The stereoselectivity observed after oral administration is due to the hepatic metabolism and the first pass effect, with an AUC(R,R)/AUC(S,S) ratio of 0.5.

Improved sexual behavior in male rats treated with a Chinese herbal extract: hormonal and neuronal implications.

AIM: To investigate the influence of an extract obtained from five Chinese medicinal plants on sexual behavior of adult male rats. METHODS: The extract was administered at doses of 30, 60 and 120 mg/kg by oral gavage, acutely (one time, 45 min before mating test) or subchronically (daily for 10 days) in sexually potent and sexually sluggish/impotent rats. Sexual behavior, serum levels of luteinizing hormone (LH) and testosterone (T) were evaluated in treated rats and compared with controls receiving vehicle. The effect of the extract on central dopaminergic neurotransmission was assessed in the nucleus accumbens using a microdialysis technique. RESULTS: In sexually potent rats, both acute and subchronic treatment with the extract dosed at 30 and 60 mg/kg reduced mount latency and intromission latency. In sluggish/impotent rats, the acutely administered extract at the dose of 60 mg/kg shortened ejaculation latency, whereas subchronically administered at the doses of 30 and 60 mg/kg, reduced mount, intromission and ejaculation latencies, increasing also the percentage of mounting and ejaculating rats. The extract dosed at 60 mg/kg significantly increased LH and T following acute and subchronic administration and increased 3,4-dihydroxyphenylacetic acid levels in the nucleus accumbens, 30 min after the acute administration. CONCLUSION: The improvement in both appetitive and consummatory components of sexual behavior observed in male rats treated with the extract could be ascribed to increased serum T level in parallel with the activation of the central dopaminergic system.

Varicela (Catapora) na gestação / Varicella (Chickenpox) in pregnancy

Infecção primária por varicela durante o primeiro e segundo trimestre de gravidez pode aumentar o risco de síndrome de varicela congênita em 0,5-1,5 porcento sobre o risco basal de malformações congênitas severas. A infecção no terceiro trimestre pode conduzir a pneumonia materna, que pode ser letal se não tratada adequadamente. Ao contrário da infecção primária na gravidez, não estão descritas complicações fetais pelo herpes zoster, exceto na sua forma disseminada. Imunoglobulina para varicela-zoster (IGVZ) deve ser administrada o mais breve possível, preferencialmente dentro de 96 h de exposição, para prevenir infecção materna ou complicações subseqüentes. Depois de 96 h, a efetividade da IGVZ não foi avaliada. Varicela neonatal é mais severa se a erupção cutânea materna aparecer entre 5 dias antes ou 2 dias após o parto; ao recém-nascido deve ser adminisrado IGVZ imediatamente. Aciclovir intravenoso é recomendado para pneumonia materna e neonatal severas. Nenhum estudo controlado ainda avaliou a efetividade de aciclovir ou valaciclovir para profilaxia pós-exposição de gestantes ou neonatos. O advento de técnicas de imagem avançadas e a biologia molecular melhoram o diagnóstico pré-natal. Com o aumento da vacinação, é esperado que a incidência de catapora na gravidez diminua no futuro

Transferência placentária de drogas / Placental drug transfer

Grávidas podem depender do uso de medicações para minimizar os agravos da doença preexistente. A gravidez, por si só, pode causar situações que comprometem o bem-estar materno, como náuseas e vômitos, as quais necessitam de tratamento. O obstetra deve estar atento à transferência placentária de drogas e à exposição do feto a agentes teratogênicos ou tóxicos, que podem comprometer o seu desenvolvimento ou mesmo sua vida futura.O transporte através da placenta envolve o movimento de moléculas entre três compartimentos: sangue materno, citoplasma do sinciciotrofoblasto e sangue fetal. Esse movimento pode ocorrer pelos seguintes mecanismos: difusão simples, difusão facilitada, transporte ativo, bombas classe P, V, F e grande família ABC e endocitose. Com o uso de anticonvulsivantes a incidência de malformações maiores em recém-nascidos expostos é de 4 a 6 por cento, comparado com 2 a 4 por cento na população geral. A politerapia é mais lesiva, especialmente se o ácido valpróico e a hidantoína fazem parte da associação. Para as pacientes epilépticas clinicamente assintomáticas há dois anos recomenda-se a suspensão da drogas em uso, porém se apresentam crises, torna-se prudente consultar neurologista para discussão da terapia anticonvulsivante com melhores benefícios e menores efeitos colaterais. Os anestésicos locais e os opióides são largamente utilizados durante a resolução da gestação. A lidocaína utilizada como anestésico por via perineal para episiotomia, na dose fixa de 400 mg, apresenta alta concentração plasmática materna e alta taxa de transferência placentária no momento do nascimento, que vem alertar para o cuidado no uso de doses repetidas. A bupivacaína administrada por via epidural representa anestésico seguro, apresentando-se na forma racêmica e com transferência placentária em torno de 30 por cento. A fentanila, anestésico opióide, utilizado por via epidural na resolução por cesariana, na dose fixa de 0,10 mg, apresenta alta...

Pregnant women may depend on the use of medications to minimize the problems caused by preexisting disease, and pregnancy itself can cause situations that compromise the maternal well-being and that require treatment. The obstetrician should be aware of the placental transfer of drugs and of fetal exposure to teratogenic or toxic agents that might compromise the development of the fetus or even its future life.Transport through the placenta involves the movement of molecules between three compartments: maternal blood, cytoplasm of the syncytiotrophoblast, and fetal blood. This movement can occur through the following mechanisms: simple diffusion, facilitated diffusion, active transport, class P, V, F and large ABC family pumps, and endocytosis. With the use of anticonvulsants the incidence of major malformations in exposed newborns is 4 to 6 percent, compared to 2 to 4 percent in the general population. Multidrug treatment is more damaging, especially when valproic acid and hydantoin are part of the combination. The recommendation for epileptic patients who have been clinically asymptomatic for two years is to discontinue the drugs they are taking. However, if seizures occur it is advisable to consult a neurologist to discuss anticonvulsant therapy with better benefits and less side effects.Local anesthetics and opioids are extensively used during the resolution of pregnancy. Lidocaine applied by the perineal route for episiotomy at a fixed dose of 400 mg presents a high concentration in maternal plasma and a high rate of placental transfer at the time of birth, with the need for caution regarding the use of repeated doses. Bupivacaine administered by the epidural route is a safe anesthetic which is present in the racemic form and has a placental transfer of about 30 percent. Fentanyl, an opioid anesthetic used by the epidural route in resolution of cesarean section at the fixed dose of 0.10 mg, presents high rates of placental transfer...

Management of hepatic encephalopathy: role of rifaximin.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, which develops in patients with acute or chronic liver failure. It is widely accepted to be due to impairment of hepatic clearance of toxic products from the gut such as ammonia. Accumulation of ammonia induces a glutamate neurotoxicity leading to an increased tone of the gamma-aminobutyric acid A (GABA-A) receptor system in the brain which results in HE. Factors either increasing the ammonia levels (protein load, constipation, sepsis, or gastrointestinal bleeding) or potentiating the functional activity of the GABAergic system [natural benzodiazepine-like compounds (NBZDs) or exogenous benzodiazepines] may act as precipitating factors of HE. NBZDs are present in trace amounts in the blood of normal subjects and have been found to be increased in the blood of patients with liver cirrhosis, with or without HE. These compounds may derive either from the diet since they have been found in plants, vegetables and animals or from gut bacteria. The observation that intestinal bacterial flora is involved in the production of both primary agent of HE (ammonia) and precipitating factors (NBZDs) suggests that the use of nonabsorbable antibiotics such as rifaximin may be useful in preventing episodes of HE in patients with liver cirrhosis.