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In brief: In the proestrus day, the neural and endocrine signals modulate ovarian function. This study shows vagus nerve plays a role in the multisynaptic pathways of communication between the suprachiasmatic nucleus and the ovaries where such neural information determines ovulation. Abstract: The suprachiasmatic nucleus (SCN) regulates the activity of several peripheral organs through a parasympathetic-sympathetic pathway. Previously, we demonstrated that atropine (ATR) microinjection in the right SCN of rats during proestrus blocks ovulation. In the present study, we analysed whether the vagus nerve is one of the neural pathways by which the SCN regulates ovulation. For this, CIIZ-V strain cyclic rats on the day of proestrus were microinjected with a saline solution (vehicle) or ATR in the right or left SCN, which was followed by ventral laparotomy or ipsilateral vagotomy to the microinjection side. Some animal groups were sacrificed (i) on the same day of the surgery to measure oestradiol, progesterone and luteinizing hormone (LH) levels or (ii) at 24 h after surgery to evaluate ovulation. The left vagotomy in rats microinjected with ATR in the left SCN did not modify ovulation. In rats with ATR microinjection in the right SCN, the right vagotomy increased the levels of steroids and LH on the proestrus and ovulatory response. The present results suggest that the right vagus nerve plays a role in the multisynaptic pathways of communication between the SCN and the ovaries and indicate that such neural information participates in the regulation of the oestradiol and progesterone surge, which triggers the preovulatory peak of LH and determines ovulation.
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Hormônio Luteinizante , Progesterona , Feminino , Ratos , Animais , Progesterona/metabolismo , Hormônio Luteinizante/metabolismo , Núcleo Supraquiasmático/metabolismo , Ovulação/fisiologia , Estradiol/metabolismo , Atropina/farmacologia , Atropina/metabolismo , Nervo Vago/metabolismoRESUMO
In rats with polycystic ovary syndrome (PCOS) induced by injection of estradiol valerate (EV), unilateral or bilateral section of the vagus nerve restores ovulatory function in 75% of animals, suggesting that the vagus nerve participates in the development of PCOS. Since the vagus nerve is a mixed nerve through which mainly cholinergic-type information passes, the objective of the present study was to analyze whether acetylcholine (ACh) is involved in the development of PCOS. Ten-day-old rats were injected with 2.0 mg EV, and at 60 days of age, they were microinjected on the day of diestrus in the bursa of the left or right ovary with 100 or 700 mg/kg of ovarian weight atropine, a blocker of muscarinic receptors, and sacrificed for histopathological examination after the surgery. Animals with PCOS microinjected with 100 mg of atropine showed a lack of ovulation, lower serum concentrations of progesterone and testosterone, and cysts. Histology of the ovaries of animals microinjected with 700 mg of atropine showed corpus luteum and follicles at different stages of development, which was accompanied by a lower concentration of progesterone and testosterone. These results allow us to suggest that in animals with PCOS, ACh, which passes through parasympathetic innervation, is an important component in the persistence and development of the pathophysiology.
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Síndrome do Ovário Policístico , Progesterona , Animais , Atropina/farmacologia , Estradiol , Feminino , Ovulação/efeitos dos fármacos , RatosRESUMO
BACKGROUND: Polycystic ovary syndrome is characterized by hyperactivity of the ovarian sympathetic nervous system, increases in the content and release of norepinephrine, as well as decreases in the number of ß-adrenoreceptors. In the present study, ß-adrenoreceptors in the ovaries of rats with polycystic ovary syndrome were blocked and analyzed the resultant effects on ovulation, hormone secretion and the enzymes responsible for the synthesis of catecholamines. METHODS: At 60 days of age, vehicle or estradiol valerate-treated rats were injected with propranolol [10- 4 M] into the ovarian bursas on oestrus day. The animals were sacrificed on the next day of oestrus, and the ovulation response, the steroid hormone levels in the serum and the immunoreactivity of tyrosine hydroxylase and dopamine ß-hydroxylase in the ovaries were measured. RESULTS: In animals with the induction of polycystic ovary syndrome and ß-adrenoreceptor blocking, ovulation was restored in more than half of the animals and resulted in decreased hyperandrogenism with respect to the levels observed in the estradiol valerate-treated group. Tyrosine hydroxylase and dopamine ß-hydroxylase were present in the theca cells of the growing follicles and the interstitial gland. Injection of propranolol restored the tyrosine hydroxylase and ovarian dopamine ß-hydroxylase levels in rats with polycystic ovary syndrome induction. CONCLUSIONS: The results suggest that a single injection into the ovarian bursas of propranolol, a nonselective antagonist of ß-adrenoreceptor receptors, decreases the serum testosterone concentration and the formation of ovarian cysts, improving the ovulation rate that accompanies lower levels of tyrosine hydroxylase and dopamine ß-hydroxylase in the ovary.
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Ovulação/efeitos dos fármacos , Síndrome do Ovário Policístico/metabolismo , Propranolol/farmacologia , Receptores Adrenérgicos beta/metabolismo , Antagonistas Adrenérgicos beta/farmacologia , Animais , Estradiol , Estro/efeitos dos fármacos , Estro/fisiologia , Feminino , Humanos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/fisiopatologia , Ratos , Testosterona/sangue , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
NEW FINDINGS: What is the central question of this study? What is the role of the nicotinic system of the suprachiasmatic nucleus (SCN) in the regulation of follicular growth and ovulation? What is the main finding and its importance? The stimulation of the nicotinic system of the pro-oestrus rat SCN results in an increase in the number of ova shed, in the number of growing ovarian follicles and in the secretion of oestradiol. ABSTRACT: The timing of the preovulatory luteinizing hormone surge that leads to ovulation depends to a large extent on a functional circadian clock that is localized in the suprachiasmatic nucleus (SCN). The activities of the SCN are regulated by several neurotransmitter systems, including the muscarinic system. Given that acetylcholine binds to muscarinic (mAChRs) and nicotinic (nAChRs) receptors, in the present study, we analysed the effects of unilaterally stimulating nAChRs in the left or right SCN. Stimulation treatment was administered in rats in pro-oestrus at 09.00 or 19.00 h by injecting 0.3 µl of a nicotine solution (200 µm). The effects of the stimulation were assessed by evaluating the number of ova shed, the number of ovarian follicles, and the levels of oestradiol and progesterone in serum 24 h after treatment. We observed that regardless of the time (4 h after lights on, 09.00 h, or immediately after lights off, 19.00 h) or the side of the SCN treated, the unilateral microinjection of nicotine resulted in a higher number of ova shed and higher number of growing follicles in the ovaries as well as higher oestradiol serum levels. When the nicotine microinjection treatment failed to reach the SCN, the oestradiol levels in serum were similar to those of animals treated with vehicle solution. Based on the current results, we suggest that during pro-oestrus, the nicotinic neuronal information in the SCN modulates follicular growth and ovulation in a stimulatory manner.
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Folículo Ovariano/metabolismo , Ovário/metabolismo , Receptores Nicotínicos/metabolismo , Núcleo Supraquiasmático/metabolismo , Animais , Estradiol/metabolismo , Estro/metabolismo , Feminino , Hormônio Foliculoestimulante/metabolismo , Hormônio Luteinizante/metabolismo , Ovulação/metabolismo , Proestro/metabolismo , Progesterona/metabolismo , RatosRESUMO
Taenia solium cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Taenia crassiceps Both peptides have proven protective capacity against cysticercosis and are part of the highly conserved, cestode-native, 264-amino-acid long protein KE7. KE7 belongs to a ubiquitously distributed family of proteins associated with membrane processes and may participate in several vital cell pathways. The aim of this study was to identify the T. solium KE7 (TsKE7) full-length protein and to determine its immunogenic properties. Recombinant TsKE7 (rTsKE7) was expressed in Escherichia coli Rosetta2 cells and used to obtain mouse polyclonal antibodies. Anti-rTsKE7 antibodies detected the expected native protein among the 350 spots developed from T. solium cyst vesicular fluid in a mass spectrometry-coupled immune proteomic analysis. These antibodies were then used to screen a phage-displayed 7-random-peptide library to map B-cell epitopes. The recognized phages displayed 9 peptides, with the consensus motif Y(F/Y)PS sequence, which includes YYYPS (named GK-1M, for being a GK-1 mimotope), exactly matching a part of GK-1. GK-1M was recognized by 58% of serum samples from cysticercotic pigs with 100% specificity but induced weak protection against murine cysticercosis. In silico analysis revealed a universal T-cell epitope(s) in native TsKE7 potentially capable of stimulating cytotoxic T lymphocytes and helper T lymphocytes under different major histocompatibility complex class I and class II mouse haplotypes. Altogether, these results provide a rationale for the efficacy of the KETc7, rTsKE7, and GK-1 peptides as vaccines.
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Antígenos de Helmintos/imunologia , Taenia solium/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/genética , Clonagem Molecular , Cisticercose/imunologia , Cisticercose/prevenção & controle , Cisticercose/veterinária , Mapeamento de Epitopos , Escherichia coli/genética , Expressão Gênica , Camundongos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Suínos , Linfócitos T/imunologia , Taenia solium/genéticaRESUMO
MAIN CONCLUSION: Transgenic papaya callus lines expressing the components of the S3Pvac vaccine constitute a stable platform to produce an oral vaccine against cysticercosis caused by Taenia solium or T. crassiceps. The development of effective delivery systems to cope with the reduced immunogenicity of new subunit vaccines is a priority in vaccinology. Herein, experimental evidence supporting a papaya-based platform to produce needle-free, recombinant, highly immunogenic vaccines is shown. Papaya (Carica papaya) callus lines were previously engineered by particle bombardment to express the three protective peptides of the S3Pvac anti-cysticercosis vaccine (KETc7, KETc12, KETc1). Calli were propagated in vitro, and a stable integration and expression of the target genes has been maintained, as confirmed by PCR, qRT-PCR, and HPLC. These results point papaya calli as a suitable platform for long-term transgenic expression of the vaccine peptides. The previously demonstrated protective immunogenic efficacy of S3Pvac-papaya orally administered to mice is herein confirmed in a wider dose-range and formulated with different delivery vehicles, adequate for oral vaccination. This protection is accompanied by an increase in anti-S3Pvac antibody titers and a delayed hypersensitivity response against the vaccine. A significant increase in CD4+ and CD8+ lymphocyte proliferation was induced in vitro by each vaccine peptide in mice immunized with the lowest dose of S3Pvac papaya (0.56 ng of the three peptides in 0.1 µg of papaya callus total protein per mouse). In pigs, the obliged intermediate host for Taenia solium, S3Pvac papaya was also immunogenic when orally administered in a two-log dose range. Vaccinated pigs significantly increased anti-vaccine antibodies and mononuclear cell proliferation. Overall, the oral immunogenicity of this stable S3Pvac-papaya vaccine in mice and pigs, not requiring additional adjuvants, supports the interest in papaya callus as a useful platform for plant-based vaccines.
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Antígenos de Helmintos/imunologia , Carica/metabolismo , Cisticercose/veterinária , Doenças dos Suínos/prevenção & controle , Taenia solium/imunologia , Vacinas Sintéticas/imunologia , Administração Oral , Animais , Antígenos de Helmintos/administração & dosagem , Carica/genética , Carica/imunologia , Cisticercose/parasitologia , Cisticercose/prevenção & controle , Feminino , Imunização , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Plantas Geneticamente Modificadas , Suínos , Doenças dos Suínos/parasitologia , Vacinas Sintéticas/administração & dosagemRESUMO
MAIN CONCLUSION: The Taenia solium HP6/TSOL18 antigen was produced in carrot cells, yielding an immunogenic protein that induced significant protection in an experimental murine model against T. crassiceps cysticercosis when orally administered. This result supports the potential of HP6/TSOL18-carrot as a low-cost anti-cysticercosis vaccine candidate. Cysticercosis is a zoonosis caused by Taenia solium that can be prevented by interrupting the parasite life cycle through pig vaccination. Several injectable vaccine candidates have been reported, but the logistic difficulties and costs for its application limited its use in nationwide control programs. Oral plant-based vaccines can deal with this limitation, because of their easy administration and low cost. A stable expression of the HP6/TSOL18 anti-T. solium cysticercosis protective antigen in carrot calli transformed with an optimized transgene is herein reported. An antigen accumulation up to 14 µg g(-1) of dry-weight biomass was achieved in the generated carrot lines. Mouse immunization with one of the transformed calli induced both specific IgG and IgA anti-HP6/TSOL18 antibodies. A statistically significant reduction in the expected number of T. crassiceps cysticerci was observed in mice orally immunized with carrot-made HP6/TSOL18, in a similar extent to that obtained by subcutaneous immunization with recombinant HP6/TSOL18 protein. In this study, a new oral plant-made version of the HP6/TSOL18 anti-cysticercosis vaccine is reported. The vaccine candidate should be further tested against porcine cysticercosis.
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Antígenos de Helmintos/imunologia , Cisticercose/veterinária , Daucus carota/metabolismo , Taenia solium/imunologia , Administração Oral , Animais , Cisticercose/parasitologia , Cisticercose/prevenção & controle , Daucus carota/genética , Feminino , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes , Suínos , Transgenes , VacinasRESUMO
Reproduction in all mammalian species depends on the growth and maturation of ovarian follicles, that is, folliculogenesis. Follicular development can culminate with the rupture of mature follicles and the consequent expulsion of their oocytes (ovulation) or in atresia, characterized by the arrest of development and eventual degeneration. These processes are regulated by different neuroendocrine signals arising at different hypothalamic nuclei, including the suprachiasmatic nucleus (SCN). In the later, the activation of muscarinic receptors (mAChRs) and nicotinic receptors (nAChRs) by acetylcholine is essential for the regulation of the pre-ovulatory signals that stimulate the rupture of mature follicles. To evaluate the participation of the nAChRs in the SCN throughout the oestrous cycle in the regulation of the hypothalamic-pituitary-ovarian axis. For this purpose, 90-day-old adult female rats in metoestrus, dioestrus, proestrus or oestrus were microinjected into the left- or right-SCN with 0.3 µL of saline solution as vehicle or with 0.225 µg of mecamylamine (Mec), a non-selective antagonist of the nicotinic receptors, diluted in 0.3 µL of vehicle. The animals were sacrificed when they presented vaginal cornification, indicative of oestrus stage, and the effects of the unilateral pharmacological blockade of the nAChRs in the SCN on follicular development, ovulation and secretion of oestradiol and follicle-stimulating hormone (FSH) were evaluated. The microinjection of Mec decreased the serum levels of FSH, which resulted in a lower number of growing and healthy follicles and an increase in atresia. The higher percentage of atresia in pre-ovulatory follicles was related to a decrease in the number of ova shed and abnormalities in oestradiol secretion. We also detected asymmetric responses between the left and right treatments that depended on the stage of the oestrous cycle. The present results allow us to suggest that during all the stages of the oestrous cycle, cholinergic signals that act on the nAChRs in the SCN are pivotal to modulate the secretion of gonadotropins and hence the physiology of the ovaries. Further research is needed to determine if such signals are generated by the cholinergic neurons in the SCN or by cholinergic afferents to the SCN.
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BACKGROUND: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability. AIMS: To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19. METHODS: A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded. RESULTS: Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died. CONCLUSIONS: IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.
Assuntos
COVID-19 , Humanos , SARS-CoV-2 , RNA Viral , Tratamento Farmacológico da COVID-19 , Dexametasona/uso terapêuticoRESUMO
Ovarian functions are modulated by the hypothalamus-pituitary-ovary axis and neural signals. Stress modifies the activity of the sympathetic nervous system. In adult female rats, cold stress results in higher noradrenergic and steroidogenic activity of the ovary, anovulation and the presence of ovarian cysts; however, it is unknown whether this response occurs in prepubertal rats. The purpose of this study was to analyse the effects of cold stress initiated in the prepubertal stage of female rats on ovarian function. Female rats 24 days old were exposed to three, five or eight weeks of cold stress. Autopsies were performed at the end of each stress period. The parameters analysed were the number of ova shed by ovulating animals; the number of ovulating animals; the serum concentrations of progesterone, testosterone, and oestradiol; and the ovarian concentrations of norepinephrine and 3-methoxy-4-hydroxyphenyl-glycol. Our results show that chronic cold stress applied to prepubertal rats did not modify the number of ovulating animals, the total number of ova shed, or progesterone and testosterone concentrations in any of the periods analysed. Oestradiol concentration was lower in the animals exposed to five or eight weeks of stress. The ovarian norepinephrine concentration was higher in the animals exposed to three weeks of stress and was lower at eight weeks of stress. No changes in ovarian morphology were observed. Our data suggest that the changes in noradrenergic activity resulting from chronic cold stress experienced in the prepubertal stage do not modify ovarian architecture or affect the ovulatory response in adulthood.
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Resposta ao Choque Frio , Progesterona , Ratos , Animais , Feminino , Estradiol , Norepinefrina/fisiologia , TestosteronaRESUMO
Shift work disorder (SWD) may affect medical residents because their workload, academic demands and extended work hours. This condition set residents at risk of more sleep disorders. The study compared parasomnias among residents with and without shift work disorder (SWD) and weighed their relative risk (RR) for each parasomnia. One hundred twenty-six residents participated in the study. The Munich Parasomnia Screening questionnaire and the Barger Questionnaire for SWD were used for the screening of parasomnias and SWD, respectively. Means and percentages of studied variables were compared between groups. Relative risk (RR) was calculated for each type of parasomnia. The more frequent parasomnias in residents with SWD the RR (and 95% confidence intervals) were: sleep terrors, 5.60 (1.84-17.01); confusional arousals, 3.73 (1.84-7.56); sleep paralysis, 3.27 (1.53-6.93); hypnagogic/hypnopompic hallucinations, 2.55 (1.03-6.28); somniloquies, 2.45 (1.21-4.92); and nightmares, 2.01 (1.54-2.62). Our data suggest that residents who experience SWD may be at risk of having lower threshold for the occurrence of rapid eye movement (REM) and non-REM (NREM) sleep parasomnias. Additional research is needed to confirm these results, and to further identify the contribution to this association.
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During some estimations of the nuclear DNA content, based on determinations propidium iodide (PI) binding through fluorocytometry for Taenia crassiceps cysticerci, significant variation in the results were found. This initial observation led to a series of experiments designed to explain the variation. These changes could be induced by the diameter of the needles in the syringes used for the mouse to mouse transfer of the cysts. Nuclei from cysts transferred through 27-gauge needles showed 30% less PI staining than those transferred through 21 gauge needles, after 2 months infections. Reduction in PI capture induced by 27-gauge needle was reversible when the cysts were maintained in their mice hosts during 5 months. Moreover, variation in PI binding to cysticercal DNA was also found when comparing parasites grown in male versus female mice. The use of agents that homogenize the chromatin structure during PI staining, allowed demonstrating that variation were entirely due to differences in the chromatin relaxation/compaction. Additional experiments demonstrated that the higher compaction is accompanied by a reduced ability of cysts to grow in the peritoneal cavity of BALB/cAnN mice. Furthermore, proteomic analysis also showed that these changes in chromatin relaxation/compaction resulted in different levels and patterns of protein expression. Our results strongly suggest that chromatin is involved in several well characterized phenomena of the T. crassiceps murine model, and open new avenues for a detailed approach to understand such a complex host-parasite relationship.
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Cromatina/metabolismo , Cisticercose/parasitologia , Cysticercus/genética , Proteínas de Helminto/análise , Animais , Cysticercus/fisiologia , DNA de Helmintos/metabolismo , Eletroforese em Gel Bidimensional , Feminino , Citometria de Fluxo , Proteínas de Helminto/química , Ponto Isoelétrico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peso Molecular , Proteoma/análiseRESUMO
Objective: Cyclic alternanting pattern (CAP) has been considered a marker of sleep instability in children. The aim of this study was to evaluate the CAP in infants with laryngomalacia. Material and Methods: CAP were quantified in 15 infants with laryngomalacia (mean age 167.2±97.21 days) and 10 controls (mean age of 158.5±116.2 days) using polysomnography. Results: The distribution of the A2 subtypes across NREM stages in infants with laryngomalacia showed a decrease, as well as in the mean duration of CAP sequences. The A3 CAP and arousals increased in infants with laryngomalacia. Our data showed a stronger correlation between the mean duration of A1 CAP and the age in healthy controls than in infants with laryngomalacia. In accordance to previous reports infants with laryngomalacia exhibited an increase in total awake time, apnea-hypopnea index, and a decrease in N3 stage compared to controls. Discussion: Our findings add to a growing body of literature of CAP as an indicator of brain maturation.
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BACKGROUND: By end December of 2021, COVID-19 has infected around 276 million individuals and caused over 5 million deaths worldwide. Infection results in dysregulated systemic inflammation, multi-organ dysfunction, and critical illness. Cells of the central nervous system are also affected, triggering an uncontrolled neuroinflammatory response. Low doses of glucocorticoids, administered orally or intravenously, reduce mortality among moderate and severe COVID-19 patients. However, low doses administered by these routes do not reach therapeutic levels in the CNS. In contrast, intranasally administered dexamethasone can result in therapeutic doses in the CNS even at low doses. METHODS: This is an approved open-label, multicenter, randomized controlled trial to compare the effectiveness of intranasal versus intravenous dexamethasone administered in low doses to moderate and severe COVID-19 adult patients. The protocol is conducted in five health institutions in Mexico City. A total of 120 patients will be randomized into two groups (intravenous vs. intranasal) at a 1:1 ratio. Both groups will be treated with the corresponding dexamethasone scheme for 10 days. The primary outcome of the study will be clinical improvement, defined as a statistically significant reduction in the NEWS-2 score of patients with intranasal versus intravenous dexamethasone administration. The secondary outcome will be the reduction in mortality during hospitalization. CONCLUSIONS: This protocol is currently in progress to improve the efficacy of the standard therapeutic dexamethasone regimen for moderate and severe COVID-19 patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04513184 . Registered November 12, 2020. Approved by La Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) with identification number DI/20/407/04/36. People are currently being recruited.
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Tratamento Farmacológico da COVID-19 , Dexametasona/efeitos adversos , Humanos , Inflamação , Doenças Neuroinflamatórias , SARS-CoV-2 , Resultado do TratamentoRESUMO
AIMS: In the cyclic rat in estrus, the vasoactive intestinal peptide (VIP) has an impact on ovarian function, which depends on the endocrine status of the animal. In this work, we aimed to clarify the participation of VIP in the pathophysiological condition of polycystic ovary syndrome (PCOS) using a model of PCOS induced by estradiol valerate (EV-PCOS) in rats. MAIN METHODS: In the cyclic rat in estrus and in the EV-PCOS model, we analyzed the acute effects of blocking VIP receptors with the use of an antagonist (Ant-VIP) injected into the left or right ovarian bursa on the steroidogenic response and ovarian catecholamine levels. KEY FINDINGS: In the cyclic animal in estrus, the treatment with Ant-VIP in the left ovarian bursa resulted in a reduction in testosterone serum levels and in ovarian levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), without changes in 4-hydroxy-3-methoxyphenyl (MHPG) and norepinephrine (NE). When the treatment was applied on the right side, only MHPG levels increased. In the EV-PCOS model, the treatment with Ant-VIP in the left ovarian bursa increased testosterone, estradiol, MHPG, and NE levels. When the treatment was performed on the right side, progesterone levels decreased and estradiol increased, without changes in ovarian catecholamines. SIGNIFICANCE: The binding of VIP to its receptors differentially regulates steroidogenesis in the cyclic animal in estrus and in the EV-PCOS model. The blocking of VIP signaling produces changes in ovarian catecholamines.
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Modelos Animais de Doenças , Ovário/metabolismo , Síndrome do Ovário Policístico/metabolismo , Receptores de Peptídeo Intestinal Vasoativo/antagonistas & inibidores , Receptores de Peptídeo Intestinal Vasoativo/metabolismo , Animais , Catecolaminas/metabolismo , Estradiol/metabolismo , Estradiol/toxicidade , Feminino , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/tratamento farmacológico , Ratos , Testosterona/metabolismo , Peptídeo Intestinal Vasoativo/antagonistas & inibidores , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
The present study tested the hypothesis that if polycystic ovary syndrome (PCOS) results from activating the noradrenergic outflow to the ovary, unilaterally sectioning the superior ovarian nerve (SON) will result in ovulation by the denervated ovary, and the restoration of progesterone (P4), testosterone (T) and estradiol (E2) normal serum level. A single 2 mg dose of estradiol valerate (EV) to adult rats results in the development of a syndrome similar to the human PCOS. Ten-day old rats were injected with EV or vehicle solution (Vh) and were submitted to sham surgery, unilateral or bilateral sectioning of the SON at 24-days of age. The animals were sacrificed at 90 to 92 days of age, when they presented vaginal estrus preceded by a pro-estrus smear. In EV-treated animals, unilateral sectioning of the SON restored ovulation by the innervated ovary and unilateral or bilateral sectioning of the SON normalized testosterone and estradiol levels. These results suggest that aside from an increase in ovarian noradrenergic tone in the ovaries, in the pathogenesis of the PCOS participate other neural influences arriving to the ovaries via the SON, regulating spontaneous ovulation. Changes in P4, T and E2 serum levels induced by EV treatment seem to be controlled by neural signals arising from the abdominal wall and other signals arriving to the ovaries through the SON, and presents asymmetry.
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Ovário/inervação , Ovário/cirurgia , Ovulação/fisiologia , Síndrome do Ovário Policístico/reabilitação , Síndrome do Ovário Policístico/cirurgia , Algoritmos , Animais , Contagem de Células , Modelos Animais de Doenças , Estradiol/análogos & derivados , Estradiol/sangue , Estradiol/farmacologia , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Procedimentos Cirúrgicos em Ginecologia/reabilitação , Procedimentos Cirúrgicos em Ginecologia/veterinária , Oócitos/citologia , Ovário/citologia , Ovulação/sangue , Ovulação/efeitos dos fármacos , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/fisiopatologia , Progesterona/sangue , Ratos , Recuperação de Função Fisiológica/fisiologiaRESUMO
OBJECTIVE: Posttransplant anemia (PTA) in kidney recipients is a complication that has repercussions mainly of cardiovascular consequence. The objective of this study is to determine the prevalence of anemia, as well as the relationship between kidney recipient and donor sex, in the presence or absence of anemia at 12 months after kidney transplant (KT). MATERIAL AND METHODS: Observational, longitudinal study of KTs made over a 5-year period, from 2013 to 2017, in a renal transplant unit from La Raza National Health Care Medical Center. Three hundred twenty-eight records were analyzed. Hemoglobin (Hb) and the presence or absence of anemia according to the definition by the World Health Organization were analyzed. The association between kidney recipient sex and donor type (living or deceased) was evaluated. Analysis of central tendency and dispersion were performed and the mean difference was established with χ2 test or Student t test. Significance level was set at P < .05. RESULTS: The mean Hb (standard deviation) before KT was 10.38 (2.16) g/dL; Hb at 12 months was 14.47 (2.37) g/dL with an absolute increase of 4.09 g/dL. Before KT, male kidney recipients had a mean Hb of 10.54 (2.17) g/dL. At 12 months post-KT, mean Hb was 15.33 (2.25) with a change of 4.79 g/dL. Before KT, female kidney recipients had a mean Hb of 10.16 (2.13) g/dL. At 12 months post-KT, mean Hb was 13.31 (2.01) with a change of 3.15 g/dL. The difference between both sexes was 1.64 g/dL at the end of 12 months. Sixteen out of 152 (10.5%) patients had a serum creatinine (Cr) < 1.2 mg/dL and anemia; 36 out of 176 (20.5%) patients had a Cr ≥ 1.2 mg/dL and anemia (P = .014). In the bivariate logistic regression with an odds ratio of 2.047 (95% confidence interval, 1027-4078; P = .042) for higher Cr levels and the presence of persistent anemia. CONCLUSIONS: There is a prevalence of anemia in female kidney recipients and recipients of kidneys from deceased donors. There is a higher risk of persistent anemia in the case of patients with some degree of graft failure at 12 months.
Assuntos
Anemia/epidemiologia , Transplante de Rim/efeitos adversos , Doadores de Tecidos , Adulto , Anemia/etiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores SexuaisRESUMO
This study describes the first days of Taenia crassiceps infection in BALB/c substrains, BALB/cAnN and BALB/cJ, using two stocks of the same strains which were kept in different animal facilities, conventional and pathogen-free conditions, respectively. This study shows that parasite growth restriction shown by conventional BALB/cJ mice changed to parasite growth permissiveness when pathogen-free BALB/cJ mice were used. In addition, the higher number of macrophages, NK cells and intraperitoneal level of IFN-gamma found in the conventional restrictive BALB/cJ substrain vanished when the permissiveness to the parasite growth increased. No differences were found in DNA sequences of parasites collected before and after the change in the permissiveness to parasite growth which favors the possibility that the observed modifications could be due to changes in the murine strains and/or their maintenance conditions.
Assuntos
Cisticercose/imunologia , Cysticercus/crescimento & desenvolvimento , Animais , Cisticercose/parasitologia , Cysticercus/genética , Cysticercus/imunologia , DNA de Helmintos/química , DNA Intergênico/química , Feminino , Citometria de Fluxo , Interferon gama/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Peritônio/citologia , Peritônio/imunologia , Polimorfismo Genético , Organismos Livres de Patógenos EspecíficosRESUMO
In rats with polycystic ovarian syndrome (PCOS) induced by estradiol valerate (EV) injection, sectioning of the vagus nerve in the juvenile stage restores ovulatory function, suggesting that the vagus nerve stimulates the onset and development of PCOS. We analyzed whether in adult rats, the role played by the vagus nerve in PCOS development is associated with the nerve's regulation of noradrenergic activity in the celiac superior mesenteric ganglion (CSMG). Ten-day-old rats were injected with corn oil [vehicle (Vh)] or EV (2 mg). At 76 days of age, rats injected with Vh or EV were subjected to sham surgery or the sectioning of one or both vagus nerves (vagotomy). The animals were sacrificed at 80-82 days of age at vaginal estrus smear. Compared to Vh-treated animals, EV-induced PCOS rats showed a lack of ovulation, the presence of follicular cysts, and a high concentration of testosterone, without changes in noradrenaline concentrations in the CSMG or ovaries. In PCOS rats, sham surgery lowered serum testosterone and noradrenaline concentrations in the CSMG but did not restore ovulation. In animals with PCOS, vagotomy lowered testosterone concentrations to a larger degree than in sham-surgery animals. The ovaries of rats with PCOS and vagotomy showed fresh corpora lutea, indicating ovulation. In EV-treated rats with unilateral vagotomy, the concentration of noradrenaline in the CSMG was similar to that in rats with PCOS and sham surgery, which did not ovulate, while in the ovaries of PCOS rats with left or bilateral vagotomy, the noradrenaline concentration was lower than that in sham-surgery-treated animals. Our results suggest that the vagus nerve regulates PCOS development through a different mechanism than the increase in the noradrenergic activity in the CSMG; however, in ovaries, the restoration of ovulation is associated with a decrease in ovarian noradrenaline.
RESUMO
Expansion of penguin activity in maritime Antarctica, under ice thaw, increases the chances of penguin feces affecting soil microbiomes. The detail of such effects begins to be revealed. By comparing soil geochemistry and microbiome composition inside (one site) and outside (three sites) of the rookery, we found significant effects of penguin feces on both. First, penguin feces change soil geochemistry, causing increased moisture content (MC) of ornithogenic soils and nutrients C, N, P, and Si in the rookery compared to non-rookery sites, but not pH. Second, penguin feces directly affect microbiome composition in the rookery, not those outside. Specifically, we found 4,364 operational taxonomical units (OTUs) in 404 genera in six main phyla: Proteobacteria, Actinobacteria, Gemmatimonadetes, Acidobacteria, Chloroflexi, and Bacteroidetes. Although the diversity is similar among the four sites, the composition is different. For example, penguin rookery has a lower abundance of Acidobacteria, Chloroflexi, and Nitrospirae but a higher abundance of Bacteroidetes, Firmicutes, and Thermomicrobia. Strikingly, the family Clostridiaceae of Firmicutes of penguin-feces origin is most abundant in the rookery than non-rookery sites with two most abundant genera, Tissierella and Proteiniclasticum. Redundancy analysis showed all measured geochemical factors are significant in structuring microbiomes, with MC showing the highest correlation. We further extracted 21 subnetworks of microbes which contain 4,318 of the 4,364 OTUs using network analysis and are closely correlated with all geochemical factors except pH. Our finding f penguin feces, directly and indirectly, affects soil microbiome suggests an important role of penguins in soil geochemistry and microbiome structure of maritime Antarctica.