Decreased Fatty Acid Oxidation Gene Expression in Pre-Eclampsia According to the Onset and Presence of Intrauterine Growth Restriction.

Mitochondrial fatty acid oxidation (FAO) is lower in placentas with pre-eclampsia. The aim of our study was to compare the placental mRNA expression of FAO enzymes in healthy pregnancies vs. different subgroups of pre-eclampsia according to the severity, time of onset, and the presence of intrauterine growth restriction (IUGR). By using real-time qPCR, we measured the mRNA levels of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), medium-chain acyl-CoA dehydrogenase (MCAD), and carnitine palmitoyltransferases 1A and 2 (CPT1A, CPT2) on the maternal side (anchoring villi in the basal decidua) and on the fetal side (chorionic plate) of the placenta (n = 56). When compared to the controls, LCHAD, MCAD, and CPT2 mRNA had decreased in all pre-eclampsia subgroups globally and on the fetal side. On the maternal side, LCHAD mRNA was also lower in all pre-eclampsia subgroups; however, MCAD and CPT2 mRNA were only reduced in severe and early-onset disease, as well as CPT2 in IUGR (p < 0.05). There were no differences in CPT1A mRNA expression. We conclude that the FAO enzymes mRNA in the placenta was lower in pre-eclampsia, with higher reductions observed in severe, early-onset, and IUGR cases and more striking reductions on the fetal side.

The Relationship between Angiogenic Factors and Energy Metabolism in Preeclampsia.

Antiangiogenic factors are currently used for the prediction of preeclampsia. The present study aimed to evaluate the relationship between antiangiogenic factors and lipid and carbohydrate metabolism in maternal plasma and placenta. We analyzed 56 pregnant women, 30 healthy and 26 with preeclampsia (including early and late onset). We compared antiangiogenic factors soluble Fms-like Tyrosine Kinase-1 (sfLt-1), placental growth factor (PlGF), and soluble endoglin (sEng)), lipid and carbohydrate metabolism in maternal plasma, and lipid metabolism in the placenta from assays of fatty acid oxidation, fatty acid esterification, and triglyceride levels in all groups. Antiangiogenic factors sFlt-1, sFlt-1/PlGF ratio, and sEng showed a positive correlation with triglyceride, free fatty acid, and C-peptide maternal serum levels. However, there was no relationship between angiogenic factors and placental lipid metabolism parameters. Free fatty acids were predictive of elevated sFlt-1 and sEng, while C-peptide was predictive of an elevated sFlt1/PlGF ratio. The findings in this study generate a model to predict elevated antiangiogenic factor values and the relationship between them with different products of lipid and carbohydrate metabolism in maternal serum and placenta in preeclampsia.

Placental Compartmentalization of Lipid Metabolism: Implications for Singleton and Twin Pregnancies.

The study of placental lipid metabolism in uncomplicated pregnancies has not been developed in the literature to date. Its importance lies in expanding the knowledge of placental function to enable comparison with pathological pregnancies in future research. The aim of the present study was to compare the lipid metabolic activity and storage of the maternal and fetal sides of the placenta in healthy pregnancies. Moreover, we compare singleton vs. twin pregnancies to determine if placental metabolic needs differ. We analyzed placental explants from uncomplicated pregnancies, 20 from singleton and 8 from bichorial-biamniotic twin pregnancies (n = 28). Six cotyledon fragments were collected from each placenta at different distances from the umbilical cord, three close to the chorionic plate (hereinafter, we will refer to them as "fetal side") and another three close to the anchoring villi into the decidua basalis (referred to as "maternal side"). The samples were analyzed for quantitative assay placental fatty acid oxidation (FAO) and esterification (FAE) activities and triglyceride levels. The location of lipid storage in the chorionic villi was assessed by Oil red-O staining. Placental fatty acid oxidation did not show differences when comparing the maternal and fetal sides of the placenta or between single and twin pregnancies. When comparing placental sides, FAE was increased twofold in the maternal side compared to the fetal side of the placenta (P = 0.013). The tendency for lipogenesis in the placenta was exemplified by the FAE/FAO ratio, which was a 37.1% higher on the maternal side (P = 0.019). Despite this, triglyceride levels were five times higher in the fetal side than in the maternal one (P = 0.024). When analyzing singleton vs. twins, FAE was superior in the fetal side in multiple pregnancies (× 2.6, P = 0.007) and the FAE/FAO ratio was significantly higher in twins than in singleton pregnancies, on both sides of the placenta. Despite this finding, triglyceride levels were similar in twin and singleton pregnancies. Comparing the placentas of twins in the same pregnancy, there were no differences in lipid metabolism (FAO or FAE) or placental triglyceride levels between the two co-twins. Using Oil red-O staining, lipid storage in chorionic villi was found to be located on the syncytiotrophoblast cells and not in the connecting axis. The maternal side of the placenta is more active in the esterification of fatty acids, while the storage of neutral lipids concentrates on the fetal side. Moreover, multiple gestations have increased esterification without changes in the concentration of placental triglycerides, probably due to a higher transfer to the fetal circulation in response to the greater energy demand from twin fetuses.

INVESTIGACIÓN DE LA CALIDAD DE SANITIZANTES PARA MANOS SECUESTRADOS POR LA JUSTICIA EN EL MARCO DE LA PANDEMIA DE COVID-19 / Research on the quality of hand sanitizers seized by the Department of Justice in the context of COVID-19 pandemic

En el marco de la pandemia de COVID-19, las agencias reguladoras del mundo, junto a la Organización Mundial de la Salud, recomendaron el uso de sanitizantes de manos para disminuir la transmisión viral. El repentino incremento del uso de estos productos por parte de la población derivó, entre otras cosas, en la aparición de vías de comercialización no autorizadas. Como consecuencia, y por intervención de la justicia, el Laboratorio Nacional de Control del Instituto Nacional de Medicamentos recibió numerosas muestras a fin de conocer la composición cuali-cuantitativa dado que, por la apariencia de los envases y rótulos, denotaban ilegitimidad. Para ello, se llevaron a cabo diversos análisis físico-químicos por picnometría, cromatografía gaseosa y espectrofotometría de infrarrojo medio. Los resultados indicaron que, si bien las muestras analizadas contenían etanol y/o isopropanol, en la mayoría de los casos su concentración no se hallaba en los valores recomendados y casi todos los envases no cumplían con la normativa vigente de rotulado

In the context of COVID-19 pandemic, the use of hand sanitizers was recommended to reduce viral transmission by the global regulatory agencies together with the World Health Organization. The sudden increase in the use of these products by the population led, among other things, to the emergence of unauthorized marketing channels. As a result, and due to judicial intervention, numerous samples were received by the National Control Laboratory of the National Institute of Medicines in order to determine the qualitative-quantitative composition, since the appearance of the containers and labels denoted illegitimacy. To that end, various physicochemical analyses were carried out by pycnometry, gas chromatography and mid-infrared spectrophotometry. Although the analyzed samples contained ethanol and/or isopropanol, the results showed that in most cases the concentration was not within the recommended values and almost all the containers did not comply with the current labeling regulations.

Control de mercado argentino de especialidades medicinales que contienen orlistat

Todos los productos analizados demostraron su calidad al cumplir con las especificaciones de los ensayos de Identificación, Valoración y Sustancias Relacionadas establecidas en USP38. Los métodos de control resultaron ser simples, específicos, exactos, precisos y de muy fácil implementación, permitiendo una rápida identificación y valoración del principio activo Orlistat para cápsulas y comprimidos, así como una correcta cuantificación de impurezas. Este trabajo se enmarca dentro de la misión fundamental de la ANMAT Control de mercado: El ensayo de identificación para todas las especialidades medicinales analizadas resultó positivo para Orlistat. En las Tablas 1 y 2 se observan los resultados de los ensayos de valoración, uniformidad de unidades de dosificación e impurezas de evaluar la seguridad, calidad y eficacia de los productos para la salud. Es dentro de este marco donde interviene el Laboratorio Nacional de Control al determinar la calidad de las especialidades medicinales del mercado nacional con el objetivo de garantizar medicamentos seguros, eficaces y de calidad.

Effect of rabbit doe-litter separation on 24-hour changes of luteinizing hormone, follicle stimulating hormone and prolactin release in female and male suckling pups.

BACKGROUND: The daily pattern of nursing of the rabbit pup by the doe is the most important event in the day for the newborn and is neatly anticipated by them. Such anticipation presumably needs a close correlation with changes in hormones that will allow the pups to develop an appropriate behavior. Although a number of circadian functions have been examined in newborn rabbits, there is no information on 24-h pattern of gonadotropin release or on possible sex-related differences in gonadotropin or prolactin (PRL) release of pups. This study examined the 24-h changes of plasma luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) in 11 days old suckling female and male rabbits left with the mother or after short-term (i.e., 48 h) doe-litter separation. METHODS: Animals were kept under controlled light-dark cycles (16 h-8 h; lights on at 08:00 h). On day 9 post partum, groups of 6-7 female or male rabbit pups were separated from their mothers starting at 6 different time intervals in the 24 h cycle. Pups were killed 48 h after separation. At each time interval groups of male or female pups that stayed with the mother were killed as controls. Plasma, LH, FSH and PRL levels were measured by specific radioimmunoassays. RESULTS: In pups kept with their mother plasma FSH and LH maxima occurred at the first and second part of the light phase (at 13:00 and 17:00-21:00 h, respectively) (females) or as two peaks for each of the hormones (at 13:00 and 01:00 h) (males). PRL release was similar in female and male rabbit pups kept with their mother, showing a 24-h pattern with two peaks, at 13:00 and 01:00 h, respectively. Mean 24-h values of gonadotropins and PRL did not differ between sexes. Isolation of pups for 48 h augmented circulating gonadotropin and PRL levels and distorted hormone 24-h pattern to a similar extent in both sexes. CONCLUSION: Significant sex differences in 24-h changes in LH and FSH, but not in PRL, release occurred in rabbit pups kept with the doe. Separation of newborn pups from their mother augmented circulating gonadotropin and PRL levels and disrupted 24-h rhythmicity of gonadotropin and PRL release similarly in both sexes. The effect of pups' isolation can be attributed either to a modification of the circadian pacemaker or to a masking effect on some of its output overt rhythms.

24-hour changes in ACTH, corticosterone, growth hormone, and leptin levels in young male rats subjected to calorie restriction.

Calorie restriction of young male rats increases plasma prolactin, decreases luteinizing hormone (LH) and testosterone, and disrupts their 24 h secretory pattern. To study whether this could be the consequence of stress, we examined the 24 h variations of plasma adrenocorticotropic hormone (ACTH) corticosterone, growth hormone (GH), leptin, and adrenal corticosterone. Rats were submitted to a calorie restriction equivalent to a 66% of usual intake for 4 weeks, starting on day 35 of life. Controls were kept in individual cages and allowed to eat a normal calorie regimen. Significantly lower ACTH levels were detected in calorie-restricted rats. Plasma corticosterone levels during the light phase of the daily cycle were significantly higher in calorie-restricted rats. Time-of-day variation in plasma ACTH and corticosterone levels attained significance in calorie-restricted rats only, with a maximum toward the end of the resting phase. The daily pattern of adrenal gland corticosterone mirrored that of circulating corticosterone; however, calorie restriction reduced its levels. Plasma ACTH and corticosterone correlated significantly in controls only. Calorie restriction decreased plasma GH and leptin, and it distorted 24h rhythmicity. In a second study, plasma ACTH and corticosterone levels were measured in group-caged rats, isolated control rats, and calorie-restricted rats during the light phase of the daily cycle. Plasma ACTH of calorie-restricted rats was lower, and plasma corticosterone was higher, compared with isolated or group-caged controls. The changes in the secretory pattern of hormones hereby reported may be part of the neuroendocrine and metabolic mechanisms evolved to maximize survival during periods of food shortage.

Effect of litter separation on 24-hour rhythmicity of plasma prolactin, follicle-stimulating hormone and luteinizing hormone levels in lactating rabbit does.

BACKGROUND: This work describes the effect of a 48-h litter separation on 24-h patterns of plasma prolactin, FSH and LH concentration in female lactating rabbits kept under a 16:8 light-dark photoperiod (lights on at 0800 h). METHODS: Groups of 6-7 female lactating rabbits maintained with their litters or separated from them for 48 h were killed by decapitation on day 11 post-partum, at 6 different time points throughout a 24-h cycle, starting at 0900 h. Plasma levels of prolactin, FSH and LH were measured by specific double antibody radio-immunoassays. RESULTS: Plasma level of prolactin in control and separated does changed in a similar way throughout the day, showing two maxima, at 0500-0900 h and at 1700-2100 h, respectively. Litter separation significantly augmented plasma FSH and LH and disrupted their 24-h rhythmicity. CONCLUSION: Since previous studies had shown that litter separation for short periods of time augmented sexual receptivity and fertility of the doe, the changes in FSH and LH reported may influence the massive release of gonadotropin releasing hormone, LH and FSH triggered by mating or artificial insemination in litter-separated mothers.

Effect of interferon-gamma treatment on 24-hour variations in plasma ACTH, growth hormone, prolactin, luteinizing hormone and follicle-stimulating hormone of male rats.

OBJECTIVE: Interferon-gamma (IFN-gamma) is a cytokine produced by T helper cells on antigenic challenge that may affect the release of several pituitary hormones. However, in vitro or in vivo studies have yielded disparate results with stimulatory, inhibitory or absent effects of IFN on pituitary hormone release. One of the reasons for these discrepancies could be that hormone changes were commonly assessed at a single time point in the day-night cycle. In this study we measured the circadian pattern of plasma ACTH, growth hormone (GH), prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at 6 different time points within a 24-hour cycle in adult male Wistar rats. METHODS: Groups of 6-8 rats kept under light from 08:00 to 20:00 h daily received 5 daily injections intraperitoneally of human IFN-gamma (10(5) IU/kg body weight) or saline at 08:30 h. Plasma ACTH, GH, prolactin, LH and FSH levels were measured by a homologous specific double antibody RIA. RESULTS: A factorial ANOVA for main effects indicated a significant 43% increase of circulating prolactin in IFN-gamma-treated rats. Time of day changes were significant for the five hormones examined and these diurnal variations became altered by IFN-gamma administration, with a phase advance of ACTH peak, a suppression of the rest phase peak of GH, the appearance of a second peak of prolactin at an early phase of daily photoperiod, and the blunting of the 24-hour variations of plasma FSH. CONCLUSION: The data point out an effect of IFN-gamma on the mechanisms responsible for the circadian organization of pituitary hormone release.

Effect of chronic ethanol feeding on 24-hour rhythms of mitogenic responses and lymphocyte subset populations in thymus and spleen of peripubertal male rats.

This work analyzes the effect of chronic ethanol feeding on the 24-hour variation of mitogenic responses and lymphocyte subset populations in thymus and spleen. Animals were maintained under a 12:12-hour light/dark photoperiod and they received a liquid diet for 4 weeks, starting on day 35 of life. The ethanol-fed group received a similar diet to controls except that maltose was isocalorically replaced by ethanol. Ethanol replacement provided 36% of the total caloric content of the diet. Rats were killed at 6 time intervals around the clock, beginning at Zeitgeber time (ZT) 1 (ZT 0 = lights on). Under ethanol intake the splenic and thymic weight decreased. In addition, mean values of the thymic, but not of the splenic T cell number decreased, and mean values of the thymic and splenic CD8+ and CD4+CD8+ number increased. Consequently, the thymic T/B ratio and the thymic and splenic CD4+/CD8+ ratio decreased in ethanol-fed rats. At the same time there was a significant increase in the response of the thymic cells to LPS. The ethanol diet modified the 24-hour rhythmicity of thymic and splenic T, B and CD4+CD8+ cells, thymic CD4+ and splenic CD8+ cells, thymic and splenic T/B and CD4+/CD8+ ratios, as well as of mitogenic responses in both tissues. Chronic ethanol administration presumably affects the endogenous clock that modulates the circadian variation of immune responsiveness in growing rats.

24-hour pattern of circulating prolactin and growth hormone levels and submaxillary lymph node immune responses in growing male rats subjected to social isolation.

To assess the effect of social isolation of growing rats on 24-h rhythmicity of circulating prolactin and growth hormone (GH) levels and submaxillary lymph node immune responses, male Wistar rats were either individually caged or kept in groups (4-5 animals per cage) for 30 d starting on d 35 of life. Plasma prolactin and GH levels, and submaxillary lymph node lymphocyte subset populations, interferon (IFN)-gamma release and mitogenic responses to concanavalin A (Con A) and lipopolysaccharide (LPS) were determined at six time intervals during the 24 h span. Social isolation brought about changes in mean values and 24-h pattern of plasma prolactin and GH levels and lymph node immune responses. After isolation, prolactin and GH mean values decreased, and lymph node T, B, non T-non B, CD8+, and CD4+-CD8+ cells augmented, whereas lymph node CD4+/CD8+ ratio, IFN-gamma release and mitogenic responses decreased. Social isolation resulted in disruption of 24 h rhythmicity of every immune parameter tested. CD4+/CD8+ ratio, IFN-gamma release and Concanavalin A (Con A) and lipopolysaccharide (LPS) responses correlated significantly with plasma prolactin or GH levels while T/B ratio correlated with plasma prolactin levels only. B, non T-non B, and CD4+-CD8+ cells correlated negatively with plasma prolactin. Modifications in mean value and 24-h rhythmicity of plasma prolactin and GH levels are presumably involved in the effect of social isolation on immune responsiveness.

Effect of ethanol on 24-hour hormonal changes in peripubertal male rats.

We analyzed the effect of chronic (4 weeks) ethanol feeding on 24-h variation of pituitary-testicular function in peripubertal male Wistar rats by measuring circulating concentrations of prolactin, follicle-stimulating hormone, luteinizing hormone, testosterone, and thyrotropin. Animals were maintained under a 12-h light: 12-h dark photoperiod and received a liquid diet for 4 weeks, starting on day 35 of life. The ethanol-fed group received a diet similar to that provided to control animals, except that maltose was replaced isocalorically with ethanol. Ethanol replacement provided 36% of the total caloric content of the diet. Rats were killed at one of six times around the clock, beginning at zeitgeber time (ZT) 1 (ZT 0 = lights on). In ethanol-fed rats globally, secretion of prolactin was augmented, whereas secretion of follicle-stimulating hormone, luteinizing hormone, testosterone, and thyrotropin was decreased. Significant changes in the 24-h secretory pattern of circulating hormones occurred in rats receiving ethanol, including the appearance of two peaks (at ZT 1 and ZT 9), rather than one peak, of follicle-stimulating hormone during the inactive phase of the daily cycle, suppression of the maximum plasma luteinizing hormone concentration during the first part of the inactive phase, and appearance of a second peak of testosterone and prolactin during the second part of the inactive phase (at ZT 5 and ZT 9, respectively) and of a second peak of plasma thyrotropin during the first part of the active phase (at ZT 13). The significant positive correlation between testosterone and individual luteinizing hormone and prolactin concentrations in control animals was no longer observed after ethanol administration. Chronic ethanol administration presumably affects the endogenous clock that modulates the circadian variation of the pituitary-gonadal axis and thyrotropin release in growing male rats.