The percentage of CD39+ monocytes is higher in pregnant COVID-19+ patients than in nonpregnant COVID-19+ patients.

Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain "maternal-fetal tolerance", SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.

Protocolo clínico para inducción del trabajo de parto: propuesta de consenso / Clinical protocol for labor induction: consensus proposal

Resumen: ANTECEDENTES: la inducción del trabajo de parto es un procedimiento que se indica cuando existe riesgo de continuar el embarazo, en lugar de interrumpirlo. Esta maniobra enfrenta nuevas presiones, por lo que es necesario mantener actualizado el conocimiento sobre su indicación. En los últimos años se han desarrollado protocolos clínicos de mayor eficacia y seguridad, que han hecho más accesible este procedimiento. OBJETIVO: emitir un consenso actualizado y analizar los diferentes aspectos de la práctica cotidiana relacionada con la inducción del trabajo de parto. MATERIALES Y MÉTODOS: se integró un grupo de especialistas de trece instituciones nacionales para analizar diferentes aspectos de la práctica cotidiana de la inducción del trabajo de parto. Se siguió una metodología tipo Delphi de cuatro etapas, con bibliografía de normas clínicas internacionales de apoyo. CONCLUSIONES: la inducción del trabajo de parto considera los siguientes criterios: establecer con certeza que el procedimiento ofrece el mejor desenlace para la madre y el feto, confirmar la edad gestacional, realizar la evaluación obstétrica completa y contar con infraestructura para enfrentar las posibles complicaciones. Existen diferentes opciones para la inducción del trabajo de parto; sin embargo, en los últimos años se ha generalizado la prescripción de análogos de prostaglandinas (misoprostol) en todo el mundo. El especialista debe efectuar la evaluación individualizada de la paciente y el feto, con la finalidad de descartar situaciones que comprometan la salud de ambos. La complicación más común de la inducción del trabajo de parto es la taquisistolia, que puede asociarse con desprendimiento prematuro de placenta, rotura uterina y sufrimiento fetal agudo. Los óvulos vaginales de liberación controlada representan la única opción para retirar el estímulo con dinoprostona o misoprostol ante efectos adversos.

Abstract: BACKGROUND: Induction of labor is a maneuver indicated when there is a greater risk of continuing the pregnancy, than interrupting it. The induction of labor faces new pressures that make it necessary for the doctor to be permanently updated. In recent years, clinical protocols of greater efficiency and safety have been developed, which have made this procedure more accessible. OBJECTIVE: To present an updated consensus and to analyze the different aspects related to the labor induction. MATERIAL AND METHODS: A Delphi-type of consensus was conducted with participation of active obstetricians and gynecologists specialists from thirteen national institutions. Major clinical-oriented topics of induction of labor were addressed. CONCLUSIONS: To induce labor, it is necessary that at least the following situations coexist: to establish with certainty that the procedure offers the best outcome for the mother and her child, to confirm the gestational age, to make a complete obstetric evaluation and to have the infrastructure Necessary to deal with possible complications. There are several options to induce labor, although in recent years the indication of prostaglandin analogues (misoprostol) has become the most common option worldwide. The specialist must make an individualized evaluation of the patient and the fetus, in order to rule out situations that may endanger the health of any of them. The most common complication of labor induction is tachysystole, which can be complicated by premature placental abruption, uterine rupture and acute fetal distress, requiring urgent attention. Controlled-release vaginal ovules are the only option available to withdraw the stimulus with dinoprostone or misoprostol in the presence of adverse effects.

Renin-angiotensin system blockers and modulation of radiation-induced brain injury.

Radiation-induced brain injury remains a major cause of morbidity in cancer patients with primary or metastatic brain tumors. Approximately 200,000 individuals/year are treated with fractionated partial or whole-brain irradiation, and > half will survive long enough (≤6 months) to develop radiation-induced brain injury, including cognitive impairment. Although short-term treatments have shown efficacy, no long-term treatments or preventive approaches are presently available for modulating radiation-induced brain injury. Based on previous preclinical studies clearly demonstrating that renin-angiotensin system (RAS) blockers can modulate radiation-induced late effects in the kidney and lung, we and others hypothesized that RAS blockade would similarly modulate radiation-induced brain injury. Indeed, studies in the last 5 years have shown that both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor antagonists (AT(1)RAs) can prevent/ameliorate radiation-induced brain injury, including cognitive impairment, in the rat. The mechanistic basis for this RAS blocker-mediated effect remains the subject of ongoing investigations. Putative mechanisms include, i] blockade of Ang II/NADPH oxidase-mediated oxidative stress and neuroinflammation, and ii] a change in the balance of angiotensin (Ang) peptides from the pro-inflammatory and pro-oxidative Ang II to the anti-inflammatory and anti-oxidative Ang-1-7). However, given that both ACEIs and AT(1)RAs are 1] well-tolerated drugs routinely prescribed for hypertension, 2] exhibit some antitumor properties, and 3] can prevent/ameliorate radiation-induced brain injury, they appear to be ideal drugs for future clinical trials, offering the promise of improving the quality of life of brain tumor patients receiving brain irradiation.

Intracellular compartmentation of pyruvate in primary cultures of cortical neurons as detected by (13)C NMR spectroscopy with multiple (13)C labels.

The intracellular compartmentation of pyruvate in primary cultures of cortical neurons was investigated by high resolution (13)C NMR using mixtures of different pyruvate precursors conveniently labeled with (13)C or unlabeled. Cells were incubated with 1-5 mM (1-(13)C, 1,2-(13)C(2) or U-(13)C(6)) glucose only or with mixtures containing 1.5 mM (1-(13)C or U-(13)C(6)) glucose, 0.25-2.5 mM (2-(13)C or 3-(13)C) pyruvate and 1 mM malate. Extracts from cells and incubation media were analyzed by (13)C NMR to determine the relative contributions of the different precursors to the intracellular pyruvate pool. When ((13)C) glucose was used as the sole substrate fractional (13)C enrichments and (13)C isotopomer populations in lactate and glutamate carbons were compatible with a unique intracellular pool of pyruvate. When mixtures of ((13)C) glucose, ((13)C) pyruvate and malate were used, however, the fractional (13)C enrichments of the C2 and C3 carbons of lactate were higher than those of the C2 and C3 carbons of alanine and depicted a different (13)C isotopomer distribution. Moreover, neurons incubated with 1 mM (1,2-(13)C(2)) glucose and 0.25-5 mM (3-(13)C) pyruvate produced exclusively (3-(13)C) lactate, revealing that extracellular pyruvate is the unique precursor of lactate under these conditions. These results reveal the presence of two different pools of intracellular pyruvate; one derived from extracellular pyruvate, used mainly for lactate and alanine production and one derived from glucose used primarily for oxidation. A red-ox switch using the cytosolic NAD(+)/NADH ratio is proposed to modulate glycolytic flux, controlling which one of the two pyruvate pools is metabolized in the tricarboxylic acid cycle when substrates more oxidized or reduced than glucose are used.

Metabolism of (1-(13)C) glucose and (2-(13)C, 2-(2)H(3)) acetate in the neuronal and glial compartments of the adult rat brain as detected by [(13)C, (2)H] NMR spectroscopy.

Ex vivo ¿(13)C, (2)H¿ NMR spectroscopy allowed to estimate the relative sizes of neuronal and glial glutamate pools and the relative contributions of (1-(13)C) glucose and (2-(13)C, 2-(2)H(3)) acetate to the neuronal and glial tricarboxylic acid cycles of the adult rat brain. Rats were infused during 60 min in the right jugular vein with solutions containing (2-(13)C, 2-(2)H(3)) acetate and (1-(13)C) glucose or (2-(13)C, 2-(2)H(3)) acetate only. At the end of the infusion the brains were frozen in situ and perchloric acid extracts were prepared and analyzed by high resolution (13)C NMR spectroscopy (90.5 MHz). The relative sizes of the neuronal and glial glutamate pools and the contributions of acetyl-CoA molecules derived from (2-(13)C, (2)H(3)) acetate or (1-(13)C) glucose entering the tricarboxylic acid cycles of both compartments, could be determined by the analysis of (2)H-(13)C multiplets and (2)H induced isotopic shifts observed in the C4 carbon resonances of glutamate and glutamine. During the infusions with (2-(13)C, 2-(2)H(3)) acetate and (1-(13)C) glucose, the glial glutamate pool contributed 9% of total cerebral glutamate being derived from (2-(13)C, 2-(2)H(3)) acetyl-CoA (4%), (2-(13)C) acetyl-CoA (3%) and recycled (2-(13)C, 2-(2)H) acetyl-CoA (2%). The neuronal glutamate pool accounted for 91% of the total cerebral glutamate being mainly originated from (2-(13)C) acetyl-CoA (86%) and (2-(13)C, 2-(2)H) acetyl-CoA (5%). During the infusions of (2-(13)C, 2-(2)H(3)) acetate only, the glial glutamate pool contributed 73% of the cerebral glutamate, being derived from (2-(13)C, 2-(2)H(3)) acetyl-CoA (36%), (2-(13)C, 2-(2)H) acetyl-CoA (27%) and (2-(13)C) acetyl-CoA (10%). The neuronal pool contributed 27% of cerebral glutamate being formed from (2-(13)C) acetyl-CoA (11%) and recycled (2-(13)C, 2-(2)H) acetyl-CoA (16%). These results illustrate the potential of ¿(13)C, (2)H¿ NMR spectroscopy as a novel approach to investigate substrate selection and metabolic compartmentation in the adult mammalian brain.

Effects of heavy water on hepatic intracellular pH and phosphatidylcholine turnover. A 31P NMR study.

The short term effect of heavy water (2H2O) in intracellular pH (pHi) and phosphatidylcholine (PtdCho) turnover have been studied by 31P NMR spectroscopy in the perfused mouse liver metabolizing alanine. Hepatic pHi decreased from 7.19 +/- 0.01 (n = 10) to 7.01 +/- 0.03 (n = 4) after the addition of 6 mM alanine to Krebs Ringer bicarbonate (KRB) perfusion medium. Replacement of 50% of the KRB water with 2H2O during alanine perfusion inhibited the intracellular acidification induced by alanine and caused i) a decrease in the hepatic content of PtdCho, and ii) increases in phosphocholine and glycerophosphocholine, respectively. Amiloride (1 mM) of 5-(N-ethyl-N-isopropyl)-amiloride (10 microM), two previously reported inhibitors of the Na+/H+ exchangers, mimicked the effects produced by 2H2O on pHi and PtdCho turnover. Replacement of 50% of the KRB water with 2H2O or the addition of 1mM amiloride to KRB only, did not modify pHi nor increase the levels of phosphocholine of glycerophosphocholine. Thus, the observed increases are the result of alanine perfusion in the presence of 2H2O or amiloride. These results suggest that 2H2O behaves similarly to previously reported inhibitors of Na+/H+ exchange, disclosing also a novel role for PtdCho metabolism in the regulation on hepatic pHi.