Search

Background: A growing body of evidence suggests that oxidative stress plays a role in the pathophysiology of hypertension. However, the involvement of the reactive oxygen species (ROS) in the commissural nucleus of the solitary tract (commNTS) in development the of hypertension remains unclear., Method: We evaluated the hemodynamic and sympathetic responses to acute inhibition of NADPH oxidase in the commNTS in renovascular hypertensive rats. Under anesthesia, male Holtzman rats were implanted with a silver clip around the left renal artery to induce 2-kidney 1-clip (2K1C) hypertension. After six weeks, these rats were anesthetized and instrumented for recording mean arterial pressure (MAP), renal blood flow (RBF), renal vascular resistance (RVR), and renal sympathetic nerve activity (RSNA) during baseline and after injection of apocynin (nicotinamide adenine dinucleotide phosphate oxidase inhibitor), NSC 23766 (RAC inhibitor) or saline into the commNTS., Results: Apocynin into the commNTS decreased MAP, RSNA, and RVR in 2K1C rats. NSC 23766 into the commNTS decreased MAP and RSNA, without changing RVR in 2K1C rats., Conclusion: These results demonstrate that the formation of ROS in the commNTS is important to maintain sympathoexcitation and hypertension in 2K1C rats and suggest that NADPH oxidase in the commNTS could be a potential target for therapeutics in renovascular hypertension., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The pre-Bötzinger complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetized and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviors. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviors have been associated with the development and progression of diseases., Competing Interests: MM, AW, AC, JB, SC, SM, CM, RB, AA No competing interests declared, (© 2023, Melo et al.)

Melanoma is the most aggressive and lethal type of skin cancer, characterized by therapeutic resistance. In this context, the present study aimed to investigate the cytotoxic potential of manool, a diterpene from Salvia officinalis L., in human (A375) and murine (B16F10) melanoma cell lines. The analysis of cytotoxicity using the XTT assay showed the lowest IC 50 after 48 h of treatment with the manool, being 17.6 and 18.2 µg/ml for A375 and B16F10, respectively. A selective antiproliferative effect of manool was observed on the A375 cells based on the colony formation assay, showing an IC 50 equivalent to 5.6 µg/ml. The manool treatments led to 43.5% inhibition of the A375 cell migration at a concentration of 5.0 µg/ml. However, it did not affect cell migration in the B16F10 cells. Cell cycle analysis revealed that the manool interfered in the cell cycle of the A375 cells, blocking the G2/M phase. No changes in the cell cycle were observed in the B16F10 cells. Interestingly, manool did not induce apoptosis in the A375 cells, but apoptosis was observed after treatment of the B16F10 cells. Additionally, manool showed an antimelanoma effect in a reconstructed human skin model. Furthermore, in silico studies, showed that manool is stabilized in the active sites of the tubulin dimer with comparable energy concerning taxol, indicating that both structures can inhibit the proliferation of cancer cells. Altogether, it is concluded that manool, through the modulation of the cell cycle, presents a selective antiproliferative activity and a potential antimelanoma effect., (© 2022 Wiley Periodicals LLC.)

Anatomical tracing studies examining the vagal system can conflate details of sensory afferent and motor efferent neurons. Here, we used a serotype of adeno-associated virus that transports retrogradely and exhibits selective tropism for vagal afferents, to map their soma location and central termination sites within the nucleus of the solitary tract (NTS). We examined the vagal sensory afferents innervating the trachea, duodenum, stomach, or heart, and in some animals, from two organs concurrently. We observed no obvious somatotopy in the somata distribution within the nodose ganglion. The central termination patterns of afferents from different organs within the NTS overlap substantially. Convergence of vagal afferent inputs from different organs onto single NTS neurons is observed. Abdominal and thoracic afferents terminate throughout the NTS, including in the rostral NTS, where the 7th cranial nerve inputs are known to synapse. To address whether the axonal labeling produced by viral transduction is so widespread because it fills axons traveling to their targets, and not just terminal fields, we labeled pre and postsynaptic elements of vagal afferents in the NTS . Vagal afferents form multiple putative synapses as they course through the NTS, with each vagal afferent neuron distributing sensory signals to multiple second-order NTS neurons. We observe little selectivity between vagal afferents from different visceral targets and NTS neurons with common neurochemical phenotypes, with afferents from different organs making close appositions with the same NTS neuron. We conclude that specific viscerosensory information is distributed widely within the NTS and that the coding of this input is probably determined by the intrinsic properties and projections of the second-order neuron., (© 2022 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.)

Interruption of the activity of neurons in the commissural portion of the nucleus of the solitary tract (cNTS) decreases blood pressure (BP) in experimental models of hypertension, such as the spontaneously hypertensive (SH) rat. To examine whether PHOX2B expressing cNTS neurons are involved in maintaining the elevated BP, we used replication-deficient viruses with a modified Phox2 binding site promoter to express the inhibitory chemogenetic allatostatin receptor or green fluorescent protein in the cNTS. Following administration of allatostatin, we observed a depressor and bradycardic response in anesthetized SH rats that expressed the allatostatin receptor. Injection of allatostatin did not affect BP or heart rate (HR) in control SH rats expressing green fluorescent protein in the cNTS. Immunohistochemistry showed that the majority of transduced cNTS neurons were PHOX2B-immunoreactive and some also expressed tyrosine hydroxylase. We conclude that in anesthetized SH rat, the Phox2B expressing cNTS neurons maintain elevated BP., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The dopamine content in cerebral structures has been related to neuronal excitability and several approaches have been used to study this phenomenon during seizure vulnerability period. In the present work, we describe the effects of dopamine depletion after the administration of 6-hidroxidopamine (6-OHDA) into the substantia nigra pars compacta of male rats submitted to the pilocarpine model of epilepsy. Susceptibility to pilocarpine-induced status epilepticus (SE), as well as spontaneous and recurrent seizures (SRSs) frequency during the chronic period of the model were determined. Since the hippocampus is one of main structures in the development of this experimental model of epilepsy, the dopamine levels in this region were also determined after drug administration. In the first experiment, 62% (15/24) of 6-OHDA pre-treated rats and 45% (11/24) of those receiving ascorbic acid as control solution progressed to motor limbic seizures evolving to SE, after the administration of pilocarpine. Severeness of seizures during the model´s the acute period, was significantly higher in epileptic experimental rats (56.52%), than in controls (4.16%). In the second experiment, the frequency of seizures in the model's chronic phase did not significantly change between groups. Our data show that dopamine may play an important role on seizure severity in the pilo's model acute period, which seems to be due to dopamine inhibitory action on motor expression of seizure.

Naringin, considered as the main bitter component of grapefruit, requires the use of enzymes to reduce the level of this substance during juice processing. For this reason, it has been the focus of many studies. In this study, to increase the production of naringinase by Aspergillus niger cultivated in solid-state fermentation (SSF), a three-component simplex-centric mixing design along with a response surface methodology (RSM) was applied to generate statistical models and analyze the dataset. First, grapefruit peel, rice bran, and wheat bran were used for substrate selection for naringinase production and, finally, selected the best of the three inducers or their mixtures to remove the bitterness of grapefruit juice. Cultivation with 2.3 g of grapefruit peel, 2.5 g of rice bran, and 5.2 g of wheat bran and medium supplementation with a mixture of naringin, rutin, and hesperidin in the concentration of 2, 5, 4.5, and 3.0 g/L, respectively, resulted in a maximum activity of 28 U/mL. The results indicate that the sequencing procedure, which allowed the definition of an optimal mixture of components, is a new way for microorganisms to have a high naringinase yield, in particular by SSF, since our data showed a 96% increase in the production of naringinase. This dataset can help other researchers apply a mixing design to increase enzyme production., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Antibiotic resistance among bacterial pathogens is one of the most worrying problems in health systems today. To solve this problem, bacteriocins from lactic acid bacteria, especially nisin, have been proposed as an alternative for controlling multidrug-resistant bacteria. Bacteriocins are antimicrobial peptides that have activity mainly against Gram-positive strains. Nisin is one of the most studied bacteriocins and is already approved for use in food preservation. Nisin is still not approved for human clinical use, but many in vitro studies have shown its therapeutic effectiveness, especially for the control of antibiotic-resistant strains. Results from in vitro studies show the emergence of nisin-resistant bacteria after exposure to nisin. Considering that nisin has shown promising results for clinical use, studies to elucidate nisin-resistant mechanisms and the development of approaches to circumvent nisin-resistance are important. Thus, the objectives of this review are to identify the Gram-positive bacterial strains that have shown resistance to nisin, describe their resistance mechanisms and propose ways to overcome the development of nisin-resistance for its successful clinical application.

Background/aims: Furosemide is a loop diuretic widely used in clinical practice for the treatment of oedema and hypertension. The aim of this study was to determine physiological and molecular changes in the hypothalamic-neurohypophysial system as a consequence of furosemide-induced sodium depletion., Methods: Male rats were sodium depleted by acute furosemide injection (10 and 30 mg/kg) followed by access to low sodium diet and distilled water for 24 h. The renal and behavioural consequences were evaluated, while blood and brains were collected to evaluate the neuroendocrine and gene expression responses., Results: Furosemide treatment acutely increases urinary sodium and water excretion. After 24 h, water and food intake were reduced, while plasma angiotensin II and corticosterone were increased. After hypertonic saline presentation, sodium-depleted rats showed higher preference for salt. Interrogation using RNA sequencing revealed the expression of 94 genes significantly altered in the hypothalamic paraventricular nucleus (PVN) of sodium-depleted rats (31 upregulated and 63 downregulated). Out of 9 genes chosen, 5 were validated by quantitative PCR in the PVN (upregulated: Ephx2, Ndnf and Vwf; downregulated: Caprin2 and Opn3). The same genes were also assessed in the supraoptic nucleus (SON, upregulated: Tnnt1, Mis18a, Nr1d1 and Dbp; downregulated: Caprin2 and Opn3). As a result of these plastic transcriptome changes, vasopressin expression was decreased in PVN and SON, whilst vasopressin and oxytocin levels were reduced in plasma., Conclusions: We thus have identified novel genes that might regulate vasopressin gene expression in the hypothalamus controlling the magnocellular neurons secretory response to body sodium depletion and consequently hypotonic stress., (© 2020 S. Karger AG, Basel.)

Objective:  To evaluate the distribution of the main sociodemographic and clinical-pathological characteristics in women with breast cancer according to the molecular profile by immunohistochemistry., Methods:  A cross-sectional, retrospective, analytical and quantitative study was performed, with an analysis of 137 medical records from January 2015 to December 2018 of women attending the High Complexity in Oncology Unit of the city of Imperatriz, state of Maranhão, Brazil. The immunohistochemical profile of tumors based on the estrogen and progesterone receptor, Human Epidermal growth factor Receptor-type 2 (HER2) overexpression and Ki67 cell proliferation index was defined, from which six molecular subtypes were determined: luminal A, luminal B-HER2 negative, luminal B-HER2 positive, triple negative, overexpression of HER2 and inconclusive., Results:  A total of 52.6% of the patients were postmenopausal, mean age 52.1 years old, brown (56.2%), had a schooling level < 9 years (40%), staging > IIB (52.6%) and 23.4% had metastasis. Invasive ductal carcinoma accounted for 84.7%, tumor size was 2 to 5 cm (48.9%), with lymph node involvement (56.2%), axillary lymphadenectomy in 67.2%, and mastectomy in 73.7% of the patients. The most frequent molecular subtype was the luminal B-HER2 negative (36.5%), and the luminal A subtype showed characteristics of better prognosis when compared with the others., Conclusion:  It was concluded that in the association of molecular subtypes with sociodemographic and clinical-pathological characteristics, there were no statistically significant results obtained, except for complementary therapy, referring to hormone therapy, and there was a high index of metastasis at diagnosis, which was a worrying factor and indicative of failures in the screening and early diagnosis of this population., Competing Interests: The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Chemogenetics enables manipulation of neuronal activity in experimental animals. While providing information about the transduced neuron expressing a ligand-activated molecule, chemogenetics does not provide understanding about the antecedent circuit that drives that neuron's activity. For current approaches, this is not feasible, because the activating molecules are not genetically encoded. The insect allatostatin/allatostatin receptor system, a highly specific, powerful inhibitory chemogenetic approach, has this advantage, because the ligand, being a peptide, is genetically encoded. We developed viral vector-based systems to express biologically active allatostatin in neurons in vivo and allatostatin receptors in subpopulations of postsynaptic neurons. We demonstrate that activity-dependent release of allatostatin induces inhibition of allatostatin receptor-expressing neurons. We validate the approach in the vagal viscerosensory system where inhibitory, rather than the usual excitatory, viscerosensory input leads to sustained decreases in baroreceptor reflex sensitivity and bodyweight., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Heart rate and blood pressure oscillate in phase with respiratory activity. A component of these oscillations is generated centrally, with respiratory neurons entraining the activity of pre-sympathetic and parasympathetic cardiovascular neurons. Using a combination of optogenetic inhibition and excitation in vivo and in situ in rats, as well as neuronal tracing, we demonstrate that preBötzinger Complex (preBötC) neurons, which form the kernel for inspiratory rhythm generation, directly modulate cardiovascular activity. Specifically, inhibitory preBötC neurons modulate cardiac parasympathetic neuron activity whilst excitatory preBötC neurons modulate sympathetic vasomotor neuron activity, generating heart rate and blood pressure oscillations in phase with respiration. Our data reveal yet more functions entrained to the activity of the preBötC, with a role in generating cardiorespiratory oscillations. The findings have implications for cardiovascular pathologies, such as hypertension and heart failure, where respiratory entrainment of heart rate is diminished and respiratory entrainment of blood pressure exaggerated., Competing Interests: CM, AC, JB, MM, SL, JK, NK, SM, SM, AA No competing interests declared, (© 2020, Menuet et al.)

The two kidney-one clip (2K1C) renovascular hypertension depends on the renin-angiotensin system and sympathetic overactivity. The maintenance of 2K1C hypertension also depends on inputs from the carotid bodies (CB), which when activated stimulate the respiratory activity. In the present study, we investigated the importance of CB afferent activity for the ventilatory responses in 2K1C hypertensive rats and for phrenic and hypoglossal activities in in situ preparations of normotensive rats treated with angiotensin II. Silver clips were implanted around the left renal artery of male Holtzman rats (150 g) to induce renovascular hypertension. Six weeks after clipping, hypertensive 2K1C rats showed, in conscious state, elevated resting tidal volume and minute ventilation compared with the normotensive group. 2K1C rats also presented arterial alkalosis, urinary acidification, and amplified hypoxic ventilatory response. Carotid body removal (CBR), 2 wk before the experiments (4th week after clipping), significantly reduced arterial pressure and pulmonary ventilation in 2K1C rats but not in normotensive rats. Intra-arterial administration of angiotensin II in the in situ preparation of normotensive rats increased phrenic and hypoglossal activities, responses that were also reduced after CBR. Results show that renovascular hypertensive rats exhibit increased resting ventilation that depends on CB inputs. Similarly, angiotensin II increases phrenic and hypoglossal activities in in situ preparations of normotensive rats, responses that also depend on CB inputs. Results suggest that mechanisms that depend on CB inputs in renovascular hypertensive rats or during angiotensin II administration in normotensive animals increase respiratory drive.

Recent studies demonstrated an important natriorexigenic mechanism activated by aldosterone acting in the hindbrain. Studies have also shown that aldosterone effects are intensified by angiotensin II (ANG II) and vice-versa. Thus, the aim of the present work was to test if angiotensinergic mechanisms in the forebrain are involved on sodium appetite to aldosterone infused into the 4 th V and also if aldosterone into the 4th V might facilitate ingestive and cardiovascular responses to central ANG II. Male Holtzman rats with stainless steel cannulas implanted into the 4 th ventricle (4 th V) and lateral ventricle (LV) had access to 1.8% NaCl during 2 h/day. Chronic infusion of aldosterone (100 ng/h) into the 4 th V for 7 days strongly increased 1.8% NaCl intake (16.1 ± 2.2 ml/2h/day). Losartan (AT1 receptor antagonist, 50 µg/1 µl) acutely injected into the LV reduced 1.8% NaCl intake induced by aldosterone infusion into the 4 th V (8.8 ± 2.3 ml/2h/day). The pressor response to ANG II (50 ng/1 µl) into the LV increased in rats treated with aldosterone into the 4 th V (45 ± 5 mmHg, vs. vehicle infusion: 26 ± 4 mmHg). Similarly, fluid intake (water + 1.8% NaCl) also increased when rats receiving aldosterone infusion were treated with ANG II acutely into the LV. These results suggest that forebrain angiotensinergic mechanisms are important for sodium intake produced by aldosterone acting in the hindbrain. In addition, aldosterone in the hindbrain produces sensitization of the central pressor mechanisms activated by ANG II acting in the forebrain., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The rodent renovascular hypertension model has been used to investigate the mechanisms promoting hypertension. The importance of the carotid body for renovascular hypertension has been demonstrated. As the commissural NTS (cNTS) is the first synaptic site in the central nervous system that receives information from carotid body chemoreceptors, we evaluated the contribution of cNTS to renovascular hypertension in the present study. Normotensive male Holtzman rats were implanted with a silver clip around the left renal artery to induce two-kidney, one-clip (2K1C) hypertension. Six weeks later, isoguvacine (a GABA A agonist) or losartan (an AT1 antagonist) was injected into the cNTS, and the effects were compared with carotid body removal. Immunohistochemistry for Iba-1 and GFAP to label microglia and astrocytes, respectively, and RT-PCR for components of the renin-angiotensin system and cytokines in the NTS were also performed 6 weeks after renal surgery. The inhibition of cNTS with isoguvacine or the blockade of AT1 receptors with losartan in the cNTS decreased the blood pressure and heart rate of 2K1C rats even more than carotid body removal did. The mRNA expression of NOX2, TNF-α and IL-6, microglia, and astrocytes also increased in the cNTS of 2K1C rats compared to that of normotensive rats. These results indicate that tonically active neurons within the cNTS are essential for the maintenance of hypertension in 2K1C rats. In addition to signals from the carotid body, the present results suggest that angiotensin II directly activates the cNTS and may also induce microgliosis and astrogliosis within the NTS, which, in turn, cause oxidative stress and neuroinflammation.

A high-fat diet (HFD) induces an increase in arterial pressure and a decrease in baroreflex function, which may be associated with increased expression of angiotensin type 1 receptor (AT1R) and pro-inflammatory cytokine genes and reduced expression of the angiotensin type 2 receptor (AT2R) gene within the nucleus of the solitary tract (NTS), a key area of the brainstem involved in cardiovascular control. Thus, in the present study, we evaluated the changes in arterial pressure and gene expression of components of the renin-angiotensin system (RAS) and neuroinflammatory markers in the NTS of rats fed a HFD and treated with either an AT1R blocker or with virus-mediated AT2R overexpression in the NTS. Male Holtzman rats (300-320 g) were fed either a standard rat chow diet (SD) or HFD for 6 weeks before commencing the tests. AT1R blockade in the NTS of HFD-fed rats attenuated the increase in arterial pressure and the impairment of reflex bradycardia, whereas AT2R overexpression in the NTS only improved the baroreflex function. The HFD also increased the hypertensive and decreased the protective axis of the RAS and was associated with neuroinflammation within the NTS. The expression of angiotensin-converting enzyme and neuroinflammatory components, but not AT1R, in the NTS was reduced by AT2R overexpression in this site. Based on these data, AT1R and AT2R in the NTS are differentially involved in the cardiovascular changes induced by a HFD. Chronic inflammation and changes in the RAS in the NTS may also account for the cardiovascular responses observed in HFD-fed rats.

Cholinergic activation of the medial septal area (MSA) with carbachol produces thirst, natriuresis and antidiuresis. Hydrogen peroxide (H 2 O 2 ) injected into the medial septal area (MSA) impairs behavioral and renal responses induced by carbachol at the same site, suggesting the exogenous H 2 O 2 may modulate the responses to cholinergic activation in the MSA. In the present study, we investigated if the accumulation of endogenous H 2 O 2 in the MSA after the injection of the catalase inhibitor 3-amino-1,2,4-triazole (ATZ) also affects cholinergic responses. In addition, the effects of the combination of ATZ with a non-effective dose of H 2 O 2 in the MSA were also tested. Male Holtzman rats (280-320 g) with stainless steel cannulas implanted in the MSA were used. The treatment with ATZ (10 nmol) into the MSA partially reverted the antidiuretic effect of carbachol (10.5 ± 0.7, vs. saline + carbachol: 7.3 ± 0.6 ml/120 min), without changing carbachol-induced water intake (9.5 ± 1.9, vs. saline + carbachol: 10.7 ± 1.6 ml/60 min). The combination of a low dose of ATZ (2.5 nmol) with an ineffective dose of H 2 O 2 (0.5 μmol) into the MSA reduced carbachol-induced thirst (7.5 ± 2.0, vs. saline + carbachol: 14.9 ± 1.2 ml/15 min) and reverted the antidiuresis (8.1 ± 1.1, vs. saline + carbachol: 5.3 ± 0.9 ml/120 min). Sodium and potassium excretion were not modified regardless the treatment. Although exogenous H 2 O 2 injected in the MSA may affect most of the responses to cholinergic activation of the MSA, the antidiuresis is the response clearly modulated by endogenous H 2 O 2 ., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aldosterone infusion into the 4th ventricle (4th V), upstream the nucleus of the solitary tract (NTS), produces strong 0.3 M NaCl intake. In the present study, we investigated whether aldosterone infusion into the 4th V activates HSD2 neurons, changes renal excretion, or alters blood pressure and cardiovascular reflexes. Chronic infusion of aldosterone (100 ng/h) into the 4th V increased daily 0.3 M NaCl intake (up to 44 ± 10, vs. vehicle: 5.6 ± 3.4 ml/24 h) and also c-Fos expression in HSD2 neurons in the NTS and in non-HSD2 neurons in the NTS. Natriuresis, diuresis and positive sodium balance were present in rats that ingested 0.3 M NaCl, however, renal excretion was not modified by 4th V aldosterone in rats that had no access to NaCl. 4th V aldosterone also reduced baroreflex sensitivity (-2.8 ± 0.5, vs. vehicle: -5.1 ± 0.9 bpm/mmHg) in animals that had sodium available, without changing blood pressure. The results suggest that sodium intake induced by aldosterone infused into the 4th V is associated with activation of NTS neurons, among them the HSD2 neurons. Aldosterone infused into the 4th V in association with sodium intake also impairs baroreflex sensitivity, without changing arterial pressure., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: This study sought to compare patients with thyroid eye disease (TED) and normal controls with respect to the expression of the NR3C1, CHUK, IKBKB, FOS, NFKB and HSD11B1 genes in orbital fat (OF) and extraocular muscle (EOM)., Design and Methods: A prospective study design was used to evaluate 34 TED patients and 38 healthy controls. OF was harvested from 33 TED patients and 27 controls. EOM biopsies were obtained from 32 TED patients and 18 controls. Samples were examined by real-time PCR and evaluated using appropriate statistical analyses with a significance cut-off of P  < 0.05., Results: NR3C1 mRNA levels were higher in TED EOM (median 213 (96-376)) than those in control EOM (78 (34-138)) ( P  < 0.001), and NFKB expression was elevated in TED muscle (223 (31-520)) relative to that in control muscle (8 (6-31)) ( P  < 0.001). HSD11B1 expression was higher in TED EOM (0.78 (0.47-2.01)) than that in control EOM (0.22 (0.09-0.51)) ( P  < 0.001). Levels of CHUK, IKBKB , and FOS were higher in TED EOM (115 (20-223), 111 (54-299) and 0.11 (0.03-0.19), respectively) than those in control EOM (5.8 (2-13), 21 (5-52) and 0.05 (0.001-0.03) respectively) ( P  < 0.001)., Conclusion: Tissues involved in GO exhibited different mRNA levels of NR3C1, CHUK, IKBKB, FOS, NFKB and HSD11B1 . Gene expression in OF was similar for TED patients and controls. CHUK, IKBKB, FOS, NFKB , and HSD11B1 mRNA levels were higher in TED EOM than those in control EOM. NFKB was disproportionally elevated compared with NR3C1 ; this finding was indicative of a local proinflammatory profile., (© 2017 European Society of Endocrinology.)

Chronic infusion of aldosterone into the 4th ventricle (4th V) induces robust daily sodium intake, whereas acute injection of aldosterone into the 4th V produces no sodium intake. The inhibitory mechanism of the lateral parabrachial nucleus (LPBN) restrains sodium intake induced by different natriorexigenic stimuli and might affect the acute response to aldosterone into the 4th V. In the present study, 1.8% NaCl and water intake was tested in rats treated with acute injections of aldosterone into the 4th V combined with the blockade of the inhibitory mechanisms with injections of moxonidine (α 2 adrenergic/imidazoline agonist) or methysergide (a serotonergic antagonist) into the LPBN. Male Holtzman rats with stainless steel cannulas implanted in the 4th V and bilaterally in the LPBN were used. Aldosterone (250 or 500ng) into the 4th V combined with vehicle into the LPBN induced no 1.8% NaClintake compared to control (1.5±1.1 and 1.1±0.4, respectively, vs. vehicle into 4th V: 1.0±0.5ml/2h). However, aldosterone (250 or 500ng) into the 4th V combined with moxonidine (0.5nmol) into the LPBN induced strong ingestion of 1.8% NaCl (12.7±4.6 and 17.6±3.7ml/2h, respectively). Aldosterone (250ng) into the 4th V combined with methysergide (4μg) into the LPBN also induced 1.8% NaCl intake (17.6±5.4ml/2h). These data suggest that the inhibitory mechanisms of the LPBN counteract the facilitation of sodium intake produced by aldosterone injected into the 4th, restraining sodium intake in this condition., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

A new species of Dysalotus (family Chiasmodontidae) known only from off the Hawaiian archipelago is described here as Dysalotus pouliulii sp. nov. It differs from all other species of Dysalotus in having a greater number of teeth on the premaxilla (151-198 v. 60-138) and dentary (136-199 v. 76-132) and in a shorter upper jaw [51·9-54·9% of head length (L H ) v. 62·4-74·4% L H ] and lower jaw (64·8-67·4% in L H v. 75·3-88·1% in L H ). A key for the species of Dysalotus and an updated distribution map are provided. http://zoobank.org/urn:lsid:zoobank.org:pub:E9B5F1DC-52E0-4F53-9109-2A8E252AE8CE., (© 2016 The Fisheries Society of the British Isles.)

A new species of Characidium Reinhardt, 1867 endemic to tributaries of the upper rio Paraguaçu in the Chapada Diamantina, Bahia, Brazil, is described. The new species can be distinguished from its congeners except C. bahiense, C. bimaculatum, C. laterale, C. nana, C. nupelia, and C. xavante, by having a conspicuous peduncular blotch in addition to the basicaudal spot on the base of the middle caudal-fin rays. Among other features, the new species differs from C. bahiense, C. laterale, C. nana, C. nupelia, and C. xavante by having a complete lateral line with 32-36 perforated scales (vs. lateral line short, with 9-11 perforated scales), and from C. bimaculatum by the body pigmentation pattern, with secondary bars present (vs. absent), total bars 11-16 (vs. 10-12), peduncular blotch rounded (vs. horizontally elongated), and mature males not having a darker dorsal fin (vs. proximal third of dorsal fin darker in mature males). Characidium bimaculatum, a poorly known species from Northeastern Brazil, is redescribed.

Background: Dedicated pediatricians in emergency departments (EDs) may be beneficial, though no previous studies have assessed the related costs and benefits/harms. We aimed to evaluate the net benefits and costs of dedicated emergency pediatricians in a pediatric ED., Methods: Cost-consequences analysis of visits to a pediatric ED of a tertiary hospital. Two pediatric ED Medical Teams (MT) were compared: MT-A (May-September 2012), with general pediatrics physicians only; and MT-B (May-September 2013), with emergency dedicated pediatricians. The main outcomes analyzed were relevant clinical outcomes, patient throughput time and costs., Results: We included 8,694 children in MT-A and 9,417 in MT-B. Medication use in the ED increased from 42.3% of the children in MT-A to 49.6% in MT-B; diagnostic tests decreased from 24.2% in MT-A to 14.3% in MT-B. Hospitalization increased from 1.3% in MT-A to 3.0% in MT-B; however, there was no significant difference in diagnosis-related group relative weight of hospitalized children in MT-A and MT-B (MT-A, 0.979; MT-B, 1.075). No differences were observed in ED readmissions or in patients leaving without being seen by a physician. The patient throughput time was significantly shorter in MT-B, with faster times to first medical observation. Within the cost domains analyzed, the total expenditures per children observed in the ED were 16% lower in MT-B: 37.87 euros in MT-A; 31.97 euros in MT-B., Conclusion: The presence of dedicated emergency pediatricians in a pediatric ED was associated with significantly lower waiting times in the ED, reduced costs, and similar clinical outcomes., Competing Interests: The authors have declared that no competing interests exist.

Objective: The Hip Function Recovery Score questionnaire is an instrument that was developed for evaluating the functional recovery of patients over 60 years of age who undergo surgical treatment due to hip fractures. The objective of this study was to make a thorough transcultural translation of this questionnaire, with adaptation to the individual and cultural traits of the Brazilian population., Method: This translation method consisted of initial translation, back translation, drafting of a consensual version and pretesting with comments invited. Subsequently, a final version was drawn up after making the necessary adjustments, without altering the semantics of the questions in the original text., Results: The consensual version was applied to thirty patients over the age of 60 years who had undergone surgical treatment due to hip fractures. However, some difficulties in understanding some words and expressions were observed, and these were then replaced with terms that were more easily understood. After the final version had been drawn up, this was applied to the same patients and full understanding was achieved among some of them, without altering the semantics of the questions of the original text., Conclusion: The transcultural translation of the Hip Function Recovery Score will have an immediate impact on functional evaluations on patients over 60 years of age who underwent surgery due to hip fracture. It will subsequently be possible for other Brazilian scientific studies to use this questionnaire, which has been standardized and adapted to Brazilian culture, in order to make comparisons between results, thereby enriching Brazilian scientific production.

The clinical expression of systemic lupus erythematosus (SLE) is influenced by genetic and environmental factors and therefore varies between ethnicities. Information on the epidemiology of SLE in Brazil is scarce and practically limited to studies conducted in socioeconomically developed regions (South and Southeast). The objective of this study was to describe the clinical and immunological aspects and outcome of a cohort of patients with SLE treated at a university hospital in northeastern Brazil and compare patterns related to age at onset: childhood (cSLE), adult (aSLE), and late (lSLE). A random sample of 414 records (women: 93.5%) were reviewed. The mean age at SLE onset and the mean disease duration were 28.9 ± 10.9 years and 10.2 ± 6.6 years, respectively. Most patients had aSLE (n = 338; 81.6%), followed by cSLE (n = 60; 14.5%) and lSLE (n = 16; 3.9%). The female/male ratio was 6.5:1 in cSLE and 16.8:1 in aSLE; in lSLE, all patients were female (p = 0.05). During follow-up, the cSLE group presented higher rates of nephritis (70% vs. 52.9% vs. 12.5%; p = 0.0001) and leuko/lymphopenia (61.7% vs. 43.8% vs. 56.2%; p = 0.02). No significant differences were found for anti-dsDNA, anti-Sm, and antiphospholipid antibodies. Treatment with immunosuppressants was significantly more common, and higher doses of prednisone were used, in cSLE. The prevalence of cardiovascular diseases were more frequent in lSLE (p = 0.03). No significant differences were found between the three groups with regard to mean damage accrual (SDI), remission, and mortality. Although cSLE presented higher rates of nephritis and leuko/lymphopenia, more frequent use of immunosuppressants and higher prednisone doses than aSLE and lSLE, the three groups did not differ significantly with regard to damage accrual, remission, and mortality., (© The Author(s) 2015.)

Urophycis Gill 1864 is a genus of demersal fish composed by eight valid species with anti-tropical distributions in the western Atlantic. Only two species occur in the South Atlantic: U. brasiliensis (Kaup 1858) and U. mystacea Miranda Ribeiro 1903. These species have similar ranges from southeastern Brazil to northern Argentina, but U. brasiliensis occurs in more shallow waters than U. mystacea. Both species are important fishery resources in southern Brazil and Uruguay. Herein, we redescribe U. brasiliensis based on comparison of types and additional specimens, including the description of the Sagitta otolith, formerly place U. latus Miranda Ribeiro 1903 as a junior synonym of U. brasiliensis, and provide an updated map of distribution.

Intragastric hypertonic NaCl that simulates the ingestion of osmotically active substances by food intake induces thirst, vasopressin and oxytocin release, diuresis and natriuresis. Reactive oxygen species (ROS) produced endogenously in central areas may act modulating autonomic and behavioral responses. In the present study, we investigated the effects of H2O2 injected centrally on water intake and renal responses induced by increasing plasma osmolality with intragastric (ig) administration of 2M NaCl (2 ml/rat). Male Holtzman rats (280-320 g) with stainless steel cannula implanted in the lateral ventricle (LV) were used. Injections of H2O2 (2.5 μmol/1 μl) into the LV reduced ig 2M NaCl-induced water intake (3.1 ± 0.7, vs. PBS: 8.6 ± 1.0 ml/60 min, p<0.05), natriuresis (769 ± 93, vs. PBS: 1158 ± 168 μEq/120 min, p<0.05) and diuresis (4.1 ± 0.5, vs. PBS: 5.0 ± 0.5 ml/120 min, p<0.05). Injections of H2O2 into the LV also decreased meal associated water intake (4.9 ± 1.5, vs. PBS: 11.0 ± 1.7 ml/120 min). However, H2O2 into the LV did not modify 2% sucrose intake (3.3 ± 1.5, vs. PBS: 5.4 ± 2.3 ml/120 min) or 24h food deprivation-induced food intake (8.2 ± 2.0, vs. PBS: 11.0 ± 1.6g/120 min), suggesting that this treatment does not produce nonspecific inhibition of ingestive behaviors. The data suggest an inhibitory role for H2O2 acting centrally on thirst and natriuresis induced by hyperosmolarity and on meal-associated thirst., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The anti-malarials quinine and artemisinin were isolated from traditionally used plants (Cinchona spp. and Artemisia annua, respectively). The synthetic quinoline anti-malarials (e.g. chloroquine) and semi-synthetic artemisinin derivatives (e.g. artesunate) were developed based on these natural products. Malaria is endemic to the Amazon region where Plasmodium falciparum and Plasmodium vivax drug-resistance is of concern. There is an urgent need for new anti-malarials. Traditionally used Amazonian plants may provide new treatments for drug-resistant P. vivax and P. falciparum. Herein, the in vitro and in vivo antiplasmodial activity and cytotoxicity of medicinal plant extracts were investigated., Methods: Sixty-nine extracts from 11 plant species were prepared and screened for in vitro activity against P. falciparum K1 strain and for cytotoxicity against human fibroblasts and two melanoma cell lines. Median inhibitory concentrations (IC50) were established against chloroquine-resistant P. falciparum W2 clone using monoclonal anti-HRPII (histidine-rich protein II) antibodies in an enzyme-linked immunosorbent assay. Extracts were evaluated for toxicity against murine macrophages (IC50) and selectivity indices (SI) were determined. Three extracts were also evaluated orally in Plasmodium berghei-infected mice., Results: High in vitro antiplasmodial activity (IC50 = 6.4-9.9 µg/mL) was observed for Andropogon leucostachyus aerial part methanol extracts, Croton cajucara red variety leaf chloroform extracts, Miconia nervosa leaf methanol extracts, and Xylopia amazonica leaf chloroform and branch ethanol extracts. Paullinia cupana branch chloroform extracts and Croton cajucara red variety leaf ethanol extracts were toxic to fibroblasts and or melanoma cells. Xylopia amazonica branch ethanol extracts and Zanthoxylum djalma-batistae branch chloroform extracts were toxic to macrophages (IC50 = 6.9 and 24.7 µg/mL, respectively). Andropogon leucostachyus extracts were the most selective (SI >28.2) and the most active in vivo (at doses of 250 mg/kg, 71% suppression of P. berghei parasitaemia versus untreated controls)., Conclusions: Ethnobotanical or ethnopharmacological reports describe the anti-malarial use of these plants or the antiplasmodial activity of congeneric species. No antiplasmodial activity has been demonstrated previously for the extracts of these plants. Seven plants exhibit in vivo and or in vitro anti-malarial potential. Future work should aim to discover the anti-malarial substances present.

Objective: To assess the correlation between ultrasound (US) measurement on the calcaneus and bone densitometry (DEXA), among postmenopausal women who already presented fragility fractures., Methods: 35 postmenopausal women over 40 years of age, with the ability to walk and presenting osteoporotic fractures of the wrist or spine, without previous treatment for osteoporosis, were analyzed in a retrospective cohort. Of these, 16 were under 60 and 19 were over 60. The broadband ultrasound attenuation (BUA) and speed of sound (SOS) were compared using DEXA (L1-L4, total femur, femoral neck and wrist). Two different values of BUA were used as cutoff points for osteoporosis: BUA < 60 dB/MHz and BUA < 64 dB/MHz (P < 0.05); and SOS < 1600 m/s. The confidence interval was 95%. The DEXA and US data were plotted on dispersion graphs and, through linear regression, it was possible to establish correlations. Following this, the sample was stratified according to age (up to 60 years and 60 years and over). Thus, the values were again compared and correlated., Results: The best correlation obtained between DEXA and US was between the T-score of the wrist and BUA < 64 dB/MHz, with 92% sensitivity and 95% specificity. Better sensitivity at all DEXA sites was obtained when US was performed on patients over 60 years of age. The SOS compatible with osteoporosis was < 1592.5 m/s (89% sensitivity and 85% specificity)., Conclusion: US on the calcaneus can be used for screening the risk of osteoporosis fractures, using a cutoff of BUA < 64 dB/MHz, especially among patients over 60 years of age.

This open-label, prospective, phase 2 study evaluated the safety and efficacy of deferasirox (10 ± 5 mg/kg/d) in patients with hereditary hemochromatosis (HH) and iron overload refractory to or intolerant of phlebotomy. Ten patients were enrolled and all completed the 12-month treatment period. There were significant decreases from baseline to end of study (i.e., 12 months) in median serum ferritin (P < 0.001), mean transferrin saturation (P < 0.05), median liver iron concentration (P < 0.001), and mean alanine aminotransferase (P < 0.05). The median time to achieve serum ferritin reduction ≥50% compared to baseline was 7.53 months. The most common adverse events were mild, transient diarrhea (n = 5) and nausea (n = 2). No patient experienced an increase in serum creatinine that exceeded the upper limit of normal. These data confirm that deferasirox was well tolerated and effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Obesity is associated to several comorbidities, including nonalcoholic fatty liver disease, which implicates in isolated steatosis to steatohepatitis. The latter may progress to severe manifestations such as liver fibrosis, cirrhosis and hepatocellular carcinoma., Aim: To compare the presence of advanced liver fibrosis before and after bariatric surgery in patients of private and public health system., Methods: Patients from public and privative networks were studied before and after bariatric surgery. The presence or absence of advanced hepatic fibrosis was evaluated by NAFLD Fibrosis Score, a non-invasive method that uses age, BMI, AST/ALT ratio, albumin, platelet count and the presence or absence of hyperglycemia or diabetes. The characteristics of the two groups were compared. The established statistical significance criterion was p<0.05., Results: Were analyzed 40 patients with a mean age of 34.6±9.5 years for private network and 40.6± 10.2 years for public. The study sample, 35% were treated at private health system and 65% in the public ones, 38% male and 62% female. Preoperatively in the private network one (7.1%) patient had advanced liver fibrosis and developed to the absence of liver fibrosis after surgery. In the public eight (30.8%) patients had advanced liver fibrosis preoperatively, and at one year after the proportion fell to six (23%)., Conclusion: The non-alcoholic fatty liver disease in its advanced form is more prevalent in obese patients treated in the public network than in the treated at the private network and bariatric surgery may be important therapeutic option in both populations.

Several studies point to the increased risk of reactivation of latent tuberculosis infection (LTBI) in patients with chronic inflammatory arthritis (CIAs) after using tumour necrosis factor (TNF)a blockers. To study the incidence of active mycobacterial infections (aMI) in patients starting TNFa blockers, 262 patients were included in this study: 109 with rheumatoid arthritis (RA), 93 with ankylosing spondylitis (AS), 44 with juvenile idiopathic arthritis (JIA) and 16 with psoriatic arthritis (PsA). All patients had indication for anti-TNFa therapy. Epidemiologic and clinical data were evaluated and a simple X-ray and tuberculin skin test (TST) were performed. The control group included 215 healthy individuals. The follow-up was 48 months to identify cases of aMI. TST positivity was higher in patients with AS (37.6%) than in RA (12.8%), PsA (18.8%) and JIA (6.8%) (p < 0.001). In the control group, TST positivity was 32.7%. Nine (3.43%) patients were diagnosed with aMI. The overall incidence rate of aMI was 86.93/100,000 person-years [95% confidence interval (CI) 23.6-217.9] for patients and 35.79/100,000 person-years (95% CI 12.4-69.6) for control group (p < 0.001). All patients who developed aMI had no evidence of LTBI at the baseline evaluation. Patients with CIA starting TNFa blockers and no evidence of LTBI at baseline, particularly with nonreactive TST, may have higher risk of aMI.

This randomized double-blind crossover trial investigated the discomfort associated with 2 injection speeds, low (60 seconds) and slow (100 seconds), during inferior alveolar nerve block by using 1.8 mL of 2% lidocaine with 1 : 100,000 epinephrine. Three phases were considered: (a) mucosa perforation, (b) needle insertion, and (c) solution injection. Thirty-two healthy adult volunteers needing bilateral inferior alveolar nerve blocks at least 1 week apart were enrolled in the present study. The anesthetic procedure discomfort was recorded by volunteers on a 10-cm visual analog scale in each phase for both injection speeds. Comparison between the 2 anesthesia speeds in each phase was performed by paired t test. Results showed no statistically significant difference between injection speeds regarding perforation (P = .1016), needle placement (P = .0584), or speed injection (P = .1806). The discomfort in all phases was considered low. We concluded that the 2 injection speeds tested did not affect the volunteers' pain perception during inferior alveolar nerve blocks.

Cholinergic activation of the medial septal area (MSA) with carbachol produces thirst, natriuresis, antidiuresis and pressor response. In the brain, hydrogen peroxide (H2O2) modulates autonomic and behavioral responses. In the present study, we investigated the effects of the combination of carbachol and H2O2 injected into the MSA on water intake, renal excretion, cardiovascular responses and the activity of vasopressinergic and oxytocinergic neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Furthermore, the possible modulation of carbachol responses by H2O2 acting through K+ATP channels was also investigated. Male Holtzman rats (280-320 g) with stainless steel cannulas implanted in the MSA were used. The pre-treatment with H2O2 in the MSA reduced carbachol-induced thirst (7.9±1.0, vs. carbachol: 13.2±2.0 ml/60 min), antidiuresis (9.6±0.5, vs. carbachol: 7.0±0.8 ml/120 min,), natriuresis (385±36, vs. carbachol: 528±46 μEq/120 min) and pressor response (33±5, vs. carbachol: 47±3 mmHg). Combining H2O2 and carbachol into the MSA also reduced the number of vasopressinergic neurons expressing c-Fos in the PVN (46.4±11.2, vs. carbachol: 98.5±5.9 c-Fos/AVP cells) and oxytocinergic neurons expressing c-Fos in the PVN (38.5±16.1, vs. carbachol: 75.1±8.5 c-Fos/OT cells) and in the SON (57.8±10.2, vs. carbachol: 102.7±7.4 c-Fos/OT cells). Glibenclamide (K+ATP channel blocker) into the MSA partially reversed H2O2 inhibitory responses. These results suggest that H2O2 acting through K+ATP channels in the MSA attenuates responses induced by cholinergic activation in the same area., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

Water quality of the Jansen Lagoon (São Luís, Maranhão State, Brazil) was assessed through histological biomarkers and microbiological parameters. To this end, 29 fish specimens (11 Centropomus undecimalis and 18 Sardinella sp) and eight water samples were collected during the rainy and dry periods of 2013. The lagoon water showed thermotolerant coliform indices above the limit set forth in CONAMA Resolution 357/2005. Histological changes observed in the gills were: lifting of the respiratory epithelium, hyperplasia of the lamellar epithelium, incomplete and complete fusion of several lamellae, disorganization of the lamellae, congestion of blood vessels, aneurysms, hypertrophy of the respiratory epithelium, hemorrhage and rupture of the lamellar epithelium and parasite. The histological alteration index (HAI) average value to Sardinella sp was 31.8 and to C. undecimalis was 22.2. The average HAI value in both species corresponds to category 21-50, with tissue injuries being classified from moderate to severe. The presence of histological injuries and the HAI values indicate that the fish sampled from the Jansen Lagoon are reacting to non-specific xenobiotics present at the site.

Background: Carapa guianensis is a cultivable tree used by traditional health practitioners in the Amazon region to treat several diseases and particularly symptoms related to malaria. Abundant residual pressed seed material (RPSM) results as a by-product of carapa or andiroba oil production. The objective of this study was to evaluate the in vitro and in vivo anti-malarial activity and cytotoxicity of limonoids isolated from C. guaianensis RPSM., Methods: 6α-acetoxyepoxyazadiradione (1), andirobin (2), 6α-acetoxygedunin (3) and 7-deacetoxy-7-oxogedunin (4) (all isolated from RPSM using extraction and chromatography techniques) and 6α-hydroxy-deacetylgedunin (5) (prepared from 3) were evaluated using the micro test on the multi-drug-resistant Plasmodium falciparum K1 strain. The efficacy of limonoids 3 and 4 was then evaluated orally and subcutaneously in BALB/c mice infected with chloroquine-sensitive Plasmodium berghei NK65 strain in the 4-day suppressive test., Results: In vitro, limonoids 1-5 exhibited median inhibition concentrations (IC50) of 20.7-5.0 μM, respectively. In general, these limonoids were not toxic to normal cells (MRC-5 human fibroblasts). In vivo, 3 was more active than 4. At oral doses of 50 and 100 mg/kg/day, 3 suppressed parasitaemia versus untreated controls by 40 and 66%, respectively, evidencing a clear dose-response., Conclusion: 6α-acetoxygedunin is an abundant natural product present in C. guianensis residual seed materials that exhibits significant in vivo anti-malarial properties.

The sulfated polysaccharide (PLS) fraction of Agardhiella ramosissima was characterized by microanalysis, infrared spectroscopy, NMR and gas-liquid-chromatography-mass-spectrometry. The main constituent of PLS was the ι carrageenan. The monosaccharide composition of the PLS showed galactose, 3,6-anhydrogalactose and 6-O-methylgalactose. The PLS (30 mg kg(-1)) significantly reduced the paw oedema induced by carrageenan, dextran, histamine and serotonin and also was able to significantly inhibit leucocyte migration into the peritoneal cavity and decrease the concentration of myeloperoxidase (MPO) in paw tissue. In the antinociceptive tests, the pre-treatment with PLS reduced the number of writhes, the licking time but did not increase the latency time of response. This study demonstrates for the first time the anti-inflammatory and anti-nociceptive effects of PLS from A. ramosissima. Thus, we concluded that PLS could be a new natural tool in pain and acute inflammatory conditions., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Glucocorticoids (GCs) are key drugs in the treatment of systemic lupus erythematosus (SLE). GC dose reduction during remission is related to disease activity, GC dose used, length of treatment, and individual GC sensitivity. We compared GC receptor α (GRα) isoform and nuclear factor kappaB (NF-κB) messenger RNA quantitation and in vivo GC sensitivity between SLE patients during remission and healthy controls. We performed a cross-sectional study of 19 women aged 22-49 years, including 9 SLE patients in clinical remission taking ≤5 mg prednisone and 10 matched controls. We evaluated GC sensitivity using 2 cortisol suppression tests: a very-low-dose intravenous dexamethasone suppression test (VLD-IV-DST) and a low-dose oral dexamethasone suppression test. GRα and NF-κB mRNA were quantified using real-time polymerase chain reaction. Although basal cortisol and adrenocorticotropic hormone levels were similar between the groups, the percentage of cortisol reduction after the VLD-IV-DST was 56% lower in SLE patients than in controls (P = 0.014). GRα and NF-κB gene expression levels were similar between the groups. The low-dose oral dexamethasone test caused intense cortisol suppression in all individuals, limiting the ability of this test to discriminate individual GC sensitivity. A positive correlation was found between the extent of cortisol suppression in vivo (VLD-IV-DST) and the number of days elapsed since the last flare of lupus activity. Despite clinical remission, SLE patients displayed partial GC resistance recognized by the VLD-IV-DST. The mechanism of this resistance is unrelated to altered GRα and NF-κB mRNA expression.

Normal testosterone levels are frequently observed in women with androgenetic alopecia (AGA), suggesting the involvement of androgen sensitivity in this condition. Androgen sensitivity is related to androgen receptor (AR) messenger RNA (mRNA) production in hair follicles and is negatively related to the number of CAG repeats present in exon 1 of the AR gene. The aim of this study was to compare AR expression in AGA women with normal controls and to correlate this expression with the number of CAG repeats. Hair follicles were obtained from 27 women with AGA and 21 controls for AR gene expression analysis. AR expression was evaluated through AR mRNA quantification using real-time polymerase chain reaction and the number of CAG repeats in the AR gene was determined in complementary DNA samples obtained from hair follicles and analyzed with the Gene Scan software. AR mRNA in the frontal-parietal region was significantly higher than in the occipital region of AGA patients (paired t-test, P = 0.046). No significant difference was identified in controls (P = 0.67). Both regions in the same individual showed a significant positive correlation in AGA patients (r = 0.77; P < 0.05) and in controls (r = 0.91; P < 0.05). A negative correlation was identified between AR expression and the number of CAG repeats only in AGA patients (r = 0.510; P = 0.013). The identification of elevated AR mRNA quantitation in hair follicles is a useful tool for identifying potentially abnormal androgen sensitivity in AGA patients.