New Pregnane Glycosides from Mandevilla dardanoi and Their Anti-Inflammatory Activity.

Mandevilla Lindl. is an important genus of the Apocynaceae family, not only as ornamental plants but also for its medicinal uses. In Brazil, Mandevilla species are indicated to treat asthma and skin infections, their anti-inflammatory potential and wound healing properties are also reported in the literature. Concerning their chemical composition, this group of plants is a conspicuous producer of pregnane glycosides. Mandevilla dardanoi is an endemic species from the Brazilian semiarid region not studied by any phytochemical methods. In view of the medicinal potential of Mandevilla species, this study aimed to isolate new pregnane glycosides from M. dardanoi. To achieve this main goal, modern chromatography techniques were employed. Five new pregnane glycosides, dardanols A-E, were isolated from the roots of M. dardanoi by HPLC. Their structures were determined using extensive 1D and 2D-NMR and mass spectrometry (MSn and HRESIMS) data. The cytotoxicity and the anti-inflammatory potential of these compounds were evaluated. The first was evaluated by measuring proinflammatory cytokines and nitric oxide production by stimulated macrophages. Dardanols were able to inhibit the production of nitric oxide and reduce IL-1ß and TNF-α. The current work demonstrates the chemodiversity of Brazilian semiarid species and contributes to amplifying knowledge about the biological potential of the Mandevilla genus.

Targeted Isolation of Anti-inflammatory Lignans from Justicia aequilabris by Molecular Networking Approach.

Herein, the isolation of secondary metabolites from the aerial parts of Justicia aequilabris guided by HPLC-MSn and molecular networking analyses is reported. Twenty-two known compounds were dereplicated. Three new lignans (aequilabrines A-C (1-3)) and three known compounds (lariciresinol-4'-O-ß-glucose (4), roseoside (5), and allantoin (6)) were obtained. The anti-inflammatory activity of compounds 1-3 was evaluated in vitro by inhibiting the nitric oxide production (NO) and pro-inflammatory activity on the cytokine IL-1ß. Compounds 2 and 3 showed significant inhibitory activity against NO production, with IC50 values of 9.1 and 7.3 µM, respectively. The maximum inhibition of IL-1ß production was 23.5% (1), 27.3% (2), and 32.5% (3).

Decreased plasma H2O2 levels are associated with the pathogenesis leading to COVID-19 worsening and mortality.

Oxidative Stress (OS) is involved in the pathogenesis of COVID-19 and in the mechanisms by which SARS-CoV-2 causes injuries to tissues, leading to cytopathic hypoxia and ultimately multiple organ failure. The measurement of blood glutathione (GSH), H2O2, and catalase activity may help clarify the pathophysiology pathways of this disease. We developed and standardized a sensitive and specific chemiluminescence technique for H2O2 and GSH measurement in plasma and red blood cells of COVID-19 patients admitted to the intensive care unit (ICU). Contrary to what was expected, the plasma concentration of H2O2 was substantially reduced (10-fold) in COVID-19 patients compared to the healthy control group. From the cohort of patients discharged from the hospital and those who were deceased, the former showed a 3.6-fold and the later 16-fold H2O2 reduction compared to the healthy control. There was a 4.4 reduction of H2O2 concentration in the deceased group compared to the discharged group. Interestingly, there was no variation in GSH levels between groups, and reduced catalase activity was found in discharged and deceased patients compared to control. These data represent strong evidence that H2O2 is converted into highly reactive oxygen species (ROS), leading to the worst prognosis and death outcome in COVID-19 patients admitted to ICU. Considering the difference in the levels of H2O2 between the control group and the deceased patients, it is proposed the quantification of plasma H2O2 as a marker of disease progression and the induction of the synthesis of antioxidant enzymes as a strategy to reduce the production of oxidative stress during severe COVID-19.HighlightsH2O2 plasma levels is dramatically reduced in patients who deceased compared to those discharged and to the control group.Plasmatic quantification of H2O2 can be possibly used as a predictor of disease progression.Catalase activity is reduced in COVID-19.GSH levels remain unchanged in COVID-19 compared to the control group.

Flavonoids from Varronia dardani (Taroda) J.S. Mill (cordiaceae) and the evaluation of spasmolytic activity of its crude ethanolic extract.

Pharmacological studies show spasmolytic activity for various species of Varronia. Thus, based on the taxonomy criteria, the aim of this study was to contribute to chemical and biological knowledge, especially regarding the evaluation of spasmolytic activity of the ethanolic extract from Varronia dardani leaves (VD-EtOHL) on rat aorta and trachea, guinea-pig ileum and rat uterus. Were used High and Medium Performance Liquid Chromatography. Wistar rats and guinea-pigs were used for pharmacological assays. All experimental protocols were approved by Animal Ethics Committee of UFPB (126/2017). Two chalcones (pinostrobin chalcone and gymnogrammene), five flavanones (pinocembrin, isosakuranetin, pinostrobin, sakuranetin 4'-methyl ether, naringenin) and a flavonoid glycosilated (astragalin) were identified based on data of 1H and 13C Nuclear Magnetic Resonance. This study also showed that VD-EtOHL has a non-selective spasmolytic activity, presenting greater relaxing potency in rat uterus, suggesting that flavonoids isolated from VD-EtOHL may be responsible for spasmolytic activity of this extract.

Ivabradine possesses anticonvulsant and neuroprotective action in mice.

We analyzed whether ivabradine (IVA), a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, clinically used for angina and arrhythmia, had anticonvulsant, antioxidant and neuroprotective properties against classical seizure models. Potential molecular targets to IVA anticonvulsant effects were evaluated by molecular docking. Mice were treated with IVA (1, 10 or 20 mg/kg, IP) for 3 days, and 30 min after the last administration were injected with pentylenetetrazole (PTZ - 85 mg/kg, IP), pilocarpine (PILO 400 mg/kg, SC), picrotoxin (PICRO 10 mg/kg, IP). The following measures were performed: presence of seizures, latency for the first seizure, latency for death, percentage of survival. Antioxidant activity was investigated by determination of lipid peroxidation (MDA), reduced glutathione (GSH) and nitrite levels in the prefrontal cortex (PFC), hippocampus and striatum (ST). Immunohistochemistry analysis for cleaved caspase-3, a pro-apoptotic and degenerative marker, in hippocampal subregions namely cornu ammonis (CA)1, CA3 and dentate gyrus (DG), were also performed. IVA attenuated PTZ- and PICRO-induced seizures while presented an antioxidant effect in all brain areas studied. IVA markedly reduced cleaved caspase-3 expression in the CA1 and DG region of PICRO- and PTZ-treated mice, respectively. Molecular docking demonstrated that IVA has high energetic affinity and binding compatibility for GABAA receptor without causing channel obstruction. However, no reproducibility in the binding of IVA to N-methyl-d-aspartate (NMDA) receptor was detected. In conclusion, IVA has anticonvulsant, antioxidant and neuroprotective effects against PTZ- and PICRO-induced seizures. Also, a high affinity of IVA to GABAA receptor was predicted, representing a potential underlying mechanism to these observable effects.

Comparative study of alpha- and beta-pinene effect on PTZ-induced convulsions in mice.

Convulsions occur in response to a loss of balance between excitatory and inhibitory neurotransmitters, and the treatment for this condition consists in restore such lost balance. Many anticonvulsant drugs present side effects which may limit their use. This fact has stimulated the search for new sources of treatment from aromatic plants. Many monoterpenes commonly present in essential oils are known because of their anticonvulsant properties. The anticonvulsant effect of α- and ß-pinene, two structural isomers, is still little studied. Thus, the present work evaluated the anticonvulsant effect of α- and ß-pinene in pentylenetetrazole-induced convulsions model. Initially, the oral LD50 for α- and ß-pinene was estimated. Following the oral administration, a mild sedation was observed and no deaths were recorded; the LD50 estimated for both monoterpenes was greater than 2 000 mg/kg, p.o. Further, animals were orally treated with α-pinene (100, 200 and 400 mg/kg), ß-pinene (100, 200 and 400 mg/kg) and the equimolar mixture of α- and ß-pinene (400 mg/kg) and subjected to the pentylenetetrazole-induced convulsions model. In this model, only the dose of 400 mg/kg of the compounds was able to significantly decrease the seizure intensity. The latency of first convulsion was significantly increased by the mixture of α- and ß-pinene (400 mg/kg). In addition, ß-pinene and the mixture of the two monoterpenes, both at a dose of 400 mg/kg, significantly increased the time of death of animals. The treatment with ß-pinene and the equimolar mixture of the two monoterpenes significantly reduced hippocampal nitrite level and striatal content of dopamine (DA) and norepinephrine (NE). Taken together, the results suggest that α-pinene appears to be devoid of anticonvulsant action. This fact, however, seems to be dependent on the chemical structure of the compound, since pretreatment with the ß-pinene increased the time of death pf PTZ-treated mice, which seems to depend on the ability of the compound to reduce nitrite concentration and NE and DA content, during the pentylenetetrazole-induced seizure.

Orofacial antinociceptive effect of Mimosa tenuiflora (Willd.) Poiret.

Mimosa tenuiflora (Willd.) Poiret, popularly known in Brazil as "jurema-preta" is widely used against bronchitis, fever, headache and inflammation. Its antioxidant, anti-inflammatory and antinociceptive potential has already been reported. To assess the orofacial antinociceptive effect of M. tenuiflora, ethanolic extracts of M. tenuiflora (leaves, twigs, barks and roots) were submitted to in vitro tests of antioxidant activity. The extract with the highest antioxidant potential was partitioned and subjected to preliminary chemical prospecting, GC-MS, measurement of phenolic content and cytotoxicity tests of the fraction with the highest antioxidant activity. The nontoxic fraction with the highest antioxidant activity (FATEM) was subjected to tests of acute and chronic orofacial nociception and locomotor activity. The possible mechanisms of neuromodulation were also assessed. The EtOAc fraction, obtained from the ethanolic extract of M. tenuiflora barks, was the one with the highest antioxidant potential and nontoxic (FATEM), and Benzyloxyamine was the major constituent (34.27%). FATEM did not alter the locomotor system of mice and reduced significantly the orofacial nociceptive behavior induced by formalin, glutamate, capsaicin, cinnamaldehyde or acidic saline compared to the control group. FATEM also inhibited formalin- or mustard oil-induced temporomandibular nociception. In addition, it also reduced mustard oil-induced orofacial muscle nociception. However, FATEM did not alter hypertonic saline-induced corneal nociception. Neuropathic nociception was reversed by treatment with FATEM. The antinociceptive effect of FATEM was inhibited by naloxone, L-NAME and glibenclamide. FATEM has pharmacological potential for the treatment of acute and neuropathic orofacial pain and this effect is modulated by the opioid system, nitric oxide and ATP-sensitive potassium channels. These results lead us to studies of isolation and characterization of bioactive principles.

Clinical Outcomes of Plavix and Generic Clopidogrel for Patients Hospitalized With an Acute Coronary Syndrome.

BACKGROUND: Clopidogrel is one of the most commonly prescribed medications because of its ability to improve clinical outcomes for a broad range of cardiovascular conditions. After patent protection expired for Plavix in 2012, many healthcare systems adopted generic clopidogrel as a strategy to reduce healthcare costs. METHODS AND RESULTS: We conducted a population-based observational study to determine whether generic clopidogrel was noninferior to Plavix. Patients who were hospitalized with an acute coronary syndrome (ACS) from 2009 to 2014 in Ontario, Canada, >65 years, survived ≥7 days after discharge, were eligible for inclusion. The primary outcome was a composite of death and recurrent ACS at 1 year. The noninferiority margin was prespecified at a relative hazard difference of 10%. Inverse propensity of treatment weighting of the propensity score was used to account for differences in baseline characteristics between the treatment groups. The effect of clopidogrel on the hazard of clinical outcomes was estimated using a Cox proportional hazards model within the propensity-weighted cohort using Plavix as a reference. Our study included 24 530 patients with ACS, 12 643 were prescribed Plavix and 11 887 were prescribed generic clopidogrel at hospital discharge. The mean age was 77 years, 57% were men, and 21% had an ST-segment-elevation myocardial infarction. At 1 year, 17.6% of patients prescribed Plavix and 17.9% of patients prescribed clopidogrel experienced the primary outcome (hazard ratio, 1.02; 95% confidence interval, 0.96-1.08; P=0.005 for noninferiority). No significant differences between rates of death, all-cause readmission, ACS, stroke or transient ischemic attack, or bleeding were observed. CONCLUSIONS: Generic clopidogrel was noninferior to Plavix with respect to the composite end point of death and recurrent hospitalization for ACS at 1 year among adults >65 years after an ACS hospitalization. Our findings support generic clopidogrel in ACS, which could lead to substantial healthcare cost savings.

Modeling the photoperiodic entrainment of the plant circadian clock.

The circadian clock is an endogenous 24 hour rhythm that helps organisms anticipate and adapt to daily and seasonal variations in environment, such as the day/night cycle or changing temperatures. The plant clock is a complex network of transcription factors that regulate each other, forming interlocked feedback loops. Most of its components are light-regulated in some way, making the system highly sensitive to changes in light conditions. Here, we explore the mechanisms by which the plant clock adapts to changing day length. We first present some experimental data illustrating the variety of behaviors found in seedlings exposed to external day/night cycles different from 24h. We then use a mathematical model to characterize the response of the clock to a wide range of external cycle lengths and photoperiods. We show the existence of several domains of periodic entrainment with different ratios between the external cycle length and the period of the clock, and the presence of quasiperiodic and chaotic behaviors outside of the entrainment range. We simulate knockout mutants with impaired clock function and theoretical variants with diminished light sensitivity to highlight the role of a complex network and multiple light inputs in keeping the clock entrained over a wide range of conditions.

Stimulation of renal afferent fibers leads to activation of catecholaminergic and non-catecholaminergic neurons in the medulla oblongata.

Presympathetic neurons in the rostral ventrolateral medulla (RVLM) including the adrenergic cell groups play a major role in the modulation of several reflexes required for the control of sympathetic vasomotor tone and blood pressure (BP). Moreover, sympathetic vasomotor drive to the kidneys influence natriuresis and diuresis by inhibiting the cAMP/PKA pathway and redistributing the Na+/H+ exchanger isoform 3 (NHE3) to the body of the microvilli in the proximal tubules. In this study we aimed to evaluate the effects of renal afferents stimulation on (1) the neurochemical phenotype of Fos expressing neurons in the medulla oblongata and (2) the level of abundance and phosphorylation of NHE3 in the renal cortex. We found that electrical stimulation of renal afferents increased heart rate and BP transiently and caused activation of tyrosine hydroxylase (TH)-containing neurons in the RVLM and non-TH neurons in the NTS. Additionally, activation of the inhibitory renorenal reflex over a 30-min period resulted in increased natriuresis and diuresis associated with increased phosphorylation of NHE3 at serine 552, a surrogate for reduced activity of this exchanger, in the contralateral kidney. This effect was not dependent of BP changes considering that no effects on natriuresis or diuresis were found in the ipsilateral-stimulated kidney. Therefore, our data show that renal afferents leads to activation of catecholaminergic and non-catecholaminergic neurons in the medulla oblongata. When renorenal reflex is induced, NHE3 exchanger activity appears to be decreased, resulting in decreased sodium and water reabsorption in the contralateral kidney.

Predicting the presigmoid retrolabyrinthine space using a sigmoid sinus tomography classification: A cadaveric study.

BACKGROUND: The presigmoid retrolabyrinthine space is characterized by a widely variable size. The main structure involved in this large variability is the sigmoid sinus. Few studies have attempted to establish a reliable classification of sigmoid sinus to predict the presigmoid retrolabyrinthine space. We used tomographic mapping of human cadaver temporal bones to classify the position of sigmoid sinus and performed a cadaveric study to assess the validity of a novel classification in predicting the presigmoid retrolabyrinthine space. METHODS: Ten human cadaver temporal bones were randomly selected and subjected to fine-cut computed tomography scanning to classify the position of sigmoid sinus using a reference line. The specimens were classified into medial and lateral groups and each specimen was then subjected to mastoidectomy. The groups were compared using quantitative and qualitative analysis. RESULTS: The medial group showed a larger distance between the sigmoid sinus and the external auditory canal and a shallower lateral semicircular canal. In the lateral group, the mastoidectomy was more demanding, and the Trautmann's triangle was typically narrower and often "hidden" medially to the sigmoid sinus. CONCLUSIONS: The tomographic classification proposed in this study predicts, in a cadaveric model, the presigmoid retrolabyrinthine space. It may help the surgeon select the best approach to reach the petroclival region and lead to safer neurological and otological surgeries.

The impact of previous para-areolar incision in the upper outer quadrant of the breast on the localization of the sentinel lymph node in a canine model.

OBJECTIVES: This paper discusses the influence of a para-areolar incision in the upper outer quadrant of the breast on the location of the sentinel lymph node in a canine model. METHODS: The sentinel lymph node was marked with technetium-99, which was injected into the subareolar skin of the cranial breast. After the marker had migrated to the axilla, an arcuate para-areolar incision was performed 2 cm from the nipple in the upper outer quadrant. Patent blue dye was then injected above the upper border of the incision. At the marked site, an axillary incision was made, and the sentinel lymph node was identified by gamma probe and/or by direct visualization of the dye. The agreement between the two injection sites and the two sentinel lymph node identification methods was determined. Our sample group consisted of 40 cranial breasts of 23 adult females of the species Canis familiaris. The data were analyzed by using the McNemar test and by determining the kappa agreement coefficient. RESULT: Our findings showed that in 95% of the breasts, the sentinel lymph node was identified by the injection of technetium-99 m into the subareolar region, and in 82% of the cases, the sentinel lymph node was identified by the injection of patent blue dye above the upper border of the incision. The methods agreed 82% of the time. CONCLUSIONS: Previous para-areolar incisions in the upper outer quadrant did not interfere significantly with the biopsy when the dye was injected above the upper border of the incision.

The impact of previous para-areolar incision in the upper outer quadrant of the breast on the localization of the sentinel lymph node in a canine model

OBJECTIVES: This paper discusses the influence of a para-areolar incision in the upper outer quadrant of the breast on the location of the sentinel lymph node in a canine model. METHODS: The sentinel lymph node was marked with technetium-99, which was injected into the subareolar skin of the cranial breast. After the marker had migrated to the axilla, an arcuate para-areolar incision was performed 2 cm from the nipple in the upper outer quadrant. Patent blue dye was then injected above the upper border of the incision. At the marked site, an axillary incision was made, and the sentinel lymph node was identified by gamma probe and/or by direct visualization of the dye. The agreement between the two injection sites and the two sentinel lymph node identification methods was determined. Our sample group consisted of 40 cranial breasts of 23 adult females of the species Canis familiaris. The data were analyzed by using the McNemar test and by determining the kappa agreement coefficient. RESULT: Our findings showed that in 95 percent of the breasts, the sentinel lymph node was identified by the injection of technetium-99 m into the subareolar region, and in 82 percent of the cases, the sentinel lymph node was identified by the injection of patent blue dye above the upper border of the incision. The methods agreed 82 percent of the time. CONCLUSIONS: Previous para-areolar incisions in the upper outer quadrant did not interfere significantly with the biopsy when the dye was injected above the upper border of the incision.

Flora survey of a mountain forest stretch in Garanhuns, state of Pernambuco - DOI: 10.4025/actascibiolsci.v25i1.2120 / Levantamento florístico de um trecho de floresta serrana no planalto de Garanhuns, Estado de Pernambuco - DOI: 10.4025/actascibiolsci.v25i1.2120

The aim of this paper is to contribute for the flora information of marsh forests in the state of Pernambuco, Brazil. A flora survey of a semi-deciduous mountain stationary forest located in Garanhuns plateau, in Monteiro farm (latitude 8º5325S and longitude 36º2934), in Garanhuns, Pernambuco was carried out. The botanical material collection started in July 1998, representing different habits. The collected material was processed according to methods adopted in plant taxonomy. 69 species were recorded, allocated in 58 genre and 31 families, standing out by the greatest number of species to: Euphorbiaceae (06), Asteraceae and Caesalpiniaceae (05), Fabaceae, Rubiaceae, Sapindaceae and Solanaceae (04) each. Amongest the species studied, Senna rizzinii Irwin & Barneby, Casearia sylvestris Swartz, Bowdichia virgilioides Kunth and Enterolobium contortisiliquum (Vell.) Morong were verified

Este trabalho visa contribuir para o conhecimento da flora dos brejos de altitude do Estado de Pernambuco, Brasil. Foi realizado o levantamento florístico de um remanescente de floresta estacional semidecidual Montana, localizado na Fazenda Monteiro (8º5325S e 36º 2934W), Garanhuns, Pernambuco. As coletas de material botânico tiveram início no mês de julho de 1998, representando os diferentes hábitos. O material coletado foi processado segundo os métodos usuais em taxonomia. Foram registradas 69 espécies, acomodadas em 58 gêneros e 31 famílias, com destaque pelo maior número de espécies para: Euphorbiaceae (06), Asteraceae e Caesalpiniaceae (05), Fabaceae, Rubiaceae, Sapindaceae e Solanaceae (04). Dentre as espécies ocorrentes na área em estudo, verificaram-se: Senna rizzinii Irwin & Barneby, Casearia sylvestris Swartz., Bowdichia virgilioides Kunth e Enterolobium contortisiliquum (Vell.) Morong

Ciencias de la comunicación y sociedad: un diálogo para la era digital

Ciencias de la Comunicación y Sociedad un diálogo para la era digital, es un libro que recoge las principales conferencias presentadas en el VI Congreso Latinoamericano de Investigadores de la Comunicación, realizado en junio del 2002 y organizado por la ALAIC, la ABOIC y la Universidad Privada de Santa Cruz de la Sierra-UPSA, Bolivia.

New occurrence of Heliotropium L. (Boraginaceae, Heliotropioideae) in Southeast of Brazil / Nova ocorrência de Heliotropium L. (Boraginaceae, Heliotropioideae) para o Sudeste do Brasil - DOI: 10.4025/actascibiolsci.v25i2.2031

During the study of Heliotropium L. genus in the project Flora Fanerogâmica do Estado de São Paulo, it was verified that Heliotropium fruticosum L. presents a new geographical occurrence in Southeast of Brazil. Description, illustration and comments about relationships, distribution and phenology, as well as a summary of examined material are included in this paper

Durante o estudo do gênero Heliotropium L. para o projeto Flora Fanerogâmica do Estado de São Paulo, verificou-se que Heliotropium fruticosum L consiste em nova ocorrência para a região Sudeste do Brasil. São incluídos descrição, ilustração e comentários sobre afinidades, distribuição e fenologia, bem como a relação de material examinado