Antonio Carlos Romão Borges

From Inflammation to Current and Alternative Therapies Involved in Wound Healing

Wound healing is a complex event that develops in three overlapping phases: inflammatory, proliferative, and remodeling. These phases are distinct in function and histological characteristics. However, they depend on the interaction of cytokines, growth factors, chemokines, and chemical mediators from cells to perform regulatory events. In this article, we will review the pathway in the skin healing cascade, relating the major chemical inflammatory mediators, cellular and molecular, as well as demonstrating the local and systemic factors that interfere in healing and disorders associated with tissue repair deficiency. Finally, we will discuss the current therapeutic interventions in the wounds treatment, and the alternative therapies used as promising results in the development of new products with healing potential.

Antihypertensive Effect of Syzygium cumini in Spontaneously Hypertensive Rats

This study evaluated the in vivo potential antihypertensive effect of hydroalcoholic extract of Syzygium cumini leaves (HESC) in normotensive Wistar rats and in spontaneously hypertensive rats (SHR), as well as its in vitro effect on the vascular reactivity of resistance arteries. The hypotensive effect caused by intravenous infusion of HESC (0.01–4.0 mg/kg) in anesthetized Wistar rats was dose-dependent and was partially inhibited by pretreatment with atropine sulfate. SHR received HESC (0.5 g/kg/day), orally, for 8 weeks and mean arterial pressure, heart rate, and vascular reactivity were evaluated. Daily oral administration of HESC resulted in a time-dependent blood pressure reduction in SHR, with a maximum reduction of 62%. In the endothelium-deprived superior mesenteric arteries rings the treatment with HESC reduced by 40% the maximum effect (E max⁡) of contraction induced by NE. The contractile response to calcium and NE of endothelium-deprived mesenteric rings isolated from untreated SHR was reduced in a concentration-dependent manner by HESC (0.1, 0.25, and 0.5 mg/mL). This study demonstrated that Syzygium cumini reduces the blood pressure and heart rate of SHR and that this antihypertensive effect is probably due to the inhibition of arterial tone and extracellular calcium influx.

The toxicity evaluation of Syzygium cumini leaves in rodents

This study aimed to evaluate the safety of the hydroalcoholic extract (HE) of Syzygium cumini (L.) Skeels, Myrtaceae, leaves in rodents. Acute toxicity was evaluated through the determination of a LD50 in mice and rats (up to 14 days). In mice, the oral administration (p.o.) of the HE (0.1 at 6 g/kg) did not cause any death. When administered by intraperitoneal route (i.p.) the HE (0.1 at 1 g/kg) caused death of the animals (LD50 of 0.489 g/kg). In rats, the HE (0.5, 1 and 2 g/kg, p.o.) did not cause any death, while by i.p., only the 2 g/kg dose was lethal to 67% of the animals. To evaluate chronic toxicity, groups of rats daily received the HE (0.05, 0.1 and 0.25 g/kg) through p.o., during 30, 90 or 180 days and the effects on behavior, body weight, feed consumed were measured. Histology, hematology and biochemical parameters were measured at the end of the treatment. After a 30-day treatment, the HE caused changes in some biochemical parameters. Histological examination of the liver, kidneys, lungs, heart, stomach, intestine and pancreas showed normal architecture suggesting no morphological disturbances. These data may mean that the HE of S. cumini does not exert acute or chronic toxic effects by oral administration.

Antiulcerogenic activity of the extracts of Struthanthus marginatus

The gastroprotective action of the aqueous extract (AE) and the hydroalcoholic extract obtained from the leaves of Struthanthus marginatus (Desr.) Blume, Loranthaceae, were performed with in vivo models in rodents using: ethanol, indomethacin or stress-induced ulcers, determination of gastric secretion and the mucus production. The scavenger activity of AE in vitro was tested by the DPPH method. The treatment with the extracts (125-1000 mg/kg) significantly inhibited ulcerative lesions in comparison with the negative control groups in all the models evaluated and demonstrated greater effectiveness of the aqueous extract. Regarding the model of gastric secretion, a reduction in volume of gastric juice and total acidity was observed, as well as an increase in the gastric pH. The treatment of rats raised the gastric mucus production. Significant DPPH scavenging activity was evident in the AE. No sign of toxicity was observed. These results show that S. marginatus possesses gastroprotective activity. There are indications that the mechanisms involved in anti-ulcer activity are related to a decrease in acid secretion and an increase in gastric mucus content. Also, there is evidence for the involvement of antioxidant activity in the gastroprotective mechanism.

Antispasmodic effect of Jatropha gossypiifolia is mediated through dual blockade of muscarinic receptors and Ca2+ channels

The antispasmodic activity of Jatropha gossypiifolia L., Euphorbiaceae, aerial parts was investigated in rodents using the mouse intestinal transit model and acetylcholine (ACh, 10-9 to 10-4 M) and calcium (CaCl2, 10-4 to 10-1 M)-induced contractions of isolated rat jejunum. Similar to atropine (1 mg/kg), oral doses of ethanolic extract (EE) of J. gossypiifolia (500, 1000 and 2000 mg/kg) produced a decrease in intestinal transit (37.6 to 57.1%) when compared with control. The ACh-induced contraction in the jejunum was inhibited by EE (0.5, 1.0 and 2.0 mg/mL), chloroformic (CF) and aqueous fractions (0.1 and 0.5 mg/mL) and methanolic subfraction (0.05 and 0.25 mg/mL), suggesting an antimuscarinic mechanism. CaCl2 - induced responses in jejunum were also attenuated in the presence of CF (0.05 and 0.1 mg/mL) implying a direct interference of CF with the influx of calcium ions in the cells. Only the organic fraction of the extract had a calcium-antagonist effect, whereas both chloroformic and aqueous fractions had anticholinergic effect. These results suggest that the antispasmodic effect of J. gossypiifolia may be due a combination of anticholinergic and calcium antagonist mechanisms.

Phytochemical Characterization of Terminalia catappa Linn. Extracts and Their antifungal Activities against Candida spp.

Terminalia catappa Linn bark is used to treat dysentery by various populations in Southeast Asian countries, and its leaves have also been used in traditional medicine to treat hepatitis in India and the Philippines. Here, the antifungal actions of crude hydro-alcoholic extract (TcHE) and fractions from T. catappa leaves were assessed via the agar diffusion and microdilution tests on Candida reference strains and clinical isolates from patients with acquired immunodeficiency syndrome (AIDS). Additionally, the potential cytotoxic effects of TcHE were assessed on cultured human peripheral blood mononuclear cells (PBMC). T. catappa fractions and sub-fractions were analyzed by gas chromatography coupled to mass spectrometry with electron impact (GC/MS/EI), high-performance liquid chromatography coupled to mass spectrometry “electrospray” ionization in positive mode (HPLC/MS/MS/ESI+) and hydrogen nuclear magnetic resonance (1HNMR). TcHE and its fractions were able to inhibit the growth of all tested Candida strains with the n-butanol (FBuOH) fraction presenting the best antifungal activity. Testing of different FBuOH sub-fractions (SF) showed that SF10 was the most active against Candida spp. Fractioning of SF10 demonstrated that 5 out of its 15 sub-fractions were active against Candida spp., with SF10.5 presenting the highest activity. Chemical analysis of SF10 detected hydrolysable tannins (punicalin, punicalagin), gallic acid and flavonoid C-glycosides. Overall, the results showed that T. catappa L. leaf extract, fractions and sub-fractions were antifungal against Candida spp. and may be useful to treat diseases caused by this fungus.

Efeito da ropivacaína na recaptação neuronal de noradrenalina em músculo liso

JUSTIFICATIVA Y OBJETIVOS: Ademas de la accion anestesica local, la ropivacaina presenta un efecto vasoconstrictor, clinicamente significativo y puede ser observado cuando de la anestesia infiltrativa, con esto lo hace un anestesico importante en el bloqueo del campo. Este trabajo tuvo por objetivo caracterizar el mecanismo de accion constrictor de la ropivacaina en musculo liso. METODO: En preparaciones separadas del conducto deferente de ratones fueron construidas curvas concentracion-efecto de noradrenalina en la ausencia o en la presencia de la ropivacaina. En otra serie de experimentos los ratones fueron tratados con reserpina (10 mg.kg-1, por la via intraperitoneal) para evaluar la reactividad de los conductos deferentes a la tiramina o noradrenalina, en la ausencia o presencia de la ropivacaina. RESULTADOS: La ropivacaina en las concentraciones de 5 o 10 µg.mL-1 potencio el efecto maximo (Emax) de la noradrenalina en un 47% y 35%, respectivamente, mientras que en las concentraciones de 50 o 100 µg.mL-1 inhibio el efecto maximo producido por este agonista. En conductos deferentes separados de ratones reserpinizados, la ropivacaina (10 o 20 µg.mL-1) potencio (150% y 25%, respectivamente) las contracciones inducidas por la noradrenalina, mientras que las concentraciones de 50 o 100 µg.mL-1 no alteraron las respuestas a la noradrenalina. CONCLUSIONES: Los resultados logrados permiten concluir que la ropivacaina bloquea la recaptacion neuronal de noradrenalina por los terminales nerviosos simpaticos.BACKGROUND AND OBJECTIVES In addition to local anesthetic action, ropivacaine has clinically significant vasoconstrictor effects, which may be observed at infiltrative anesthesia, making it an important anesthetic for field blockade. This study aimed at characterizing the constrictor mechanism of ropivacaine on smooth muscles. METHODS Norepinephrine concentration-effect curves in the absence or presence of ropivacaine were plotted on isolated preparations of vas deferens of rats. In another series of experiments rats were treated with reserpine (10 mg.kg-1, i.p.) to evaluate vas deferens reactivity to tyramine or norepinephrine, in the absence or presence of ropivacaine. RESULTS Ropivacaine 5 or 10 microg.mL-1 potentiated maximum norepinephrine effect (Emax) in 47% and 35%, respectively, while higher concentrations (50 or 100 microg.mL-1) inhibited its maximum effect. In isolated vas deferens of rats treated with reserpine, ropivacaine (10 or 20 microg.mL-1) potentiated (150% and 25%, respectively) norepinephrine-induced contractions, while higher concentrations (50 or 100 microg.mL-1) have not changed responses to norepinephrine. CONCLUSIONS Ropivacaine blocks neuronal norepinephrine reuptake by sympathetic nerve terminals.

Effect of ropivacaine on neuronal norepinephrine reuptake in smooth muscle.

JUSTIFICATIVA Y OBJETIVOS: Ademas de la accion anestesica local, la ropivacaina presenta un efecto vasoconstrictor, clinicamente significativo y puede ser observado cuando de la anestesia infiltrativa, con esto lo hace un anestesico importante en el bloqueo del campo. Este trabajo tuvo por objetivo caracterizar el mecanismo de accion constrictor de la ropivacaina en musculo liso. METODO: En preparaciones separadas del conducto deferente de ratones fueron construidas curvas concentracion-efecto de noradrenalina en la ausencia o en la presencia de la ropivacaina. En otra serie de experimentos los ratones fueron tratados con reserpina (10 mg.kg-1, por la via intraperitoneal) para evaluar la reactividad de los conductos deferentes a la tiramina o noradrenalina, en la ausencia o presencia de la ropivacaina. RESULTADOS: La ropivacaina en las concentraciones de 5 o 10 µg.mL-1 potencio el efecto maximo (Emax) de la noradrenalina en un 47% y 35%, respectivamente, mientras que en las concentraciones de 50 o 100 µg.mL-1 inhibio el efecto maximo producido por este agonista. En conductos deferentes separados de ratones reserpinizados, la ropivacaina (10 o 20 µg.mL-1) potencio (150% y 25%, respectivamente) las contracciones inducidas por la noradrenalina, mientras que las concentraciones de 50 o 100 µg.mL-1 no alteraron las respuestas a la noradrenalina. CONCLUSIONES: Los resultados logrados permiten concluir que la ropivacaina bloquea la recaptacion neuronal de noradrenalina por los terminales nerviosos simpaticos.BACKGROUND AND OBJECTIVES In addition to local anesthetic action, ropivacaine has clinically significant vasoconstrictor effects, which may be observed at infiltrative anesthesia, making it an important anesthetic for field blockade. This study aimed at characterizing the constrictor mechanism of ropivacaine on smooth muscles. METHODS Norepinephrine concentration-effect curves in the absence or presence of ropivacaine were plotted on isolated preparations of vas deferens of rats. In another series of experiments rats were treated with reserpine (10 mg.kg-1, i.p.) to evaluate vas deferens reactivity to tyramine or norepinephrine, in the absence or presence of ropivacaine. RESULTS Ropivacaine 5 or 10 microg.mL-1 potentiated maximum norepinephrine effect (Emax) in 47% and 35%, respectively, while higher concentrations (50 or 100 microg.mL-1) inhibited its maximum effect. In isolated vas deferens of rats treated with reserpine, ropivacaine (10 or 20 microg.mL-1) potentiated (150% and 25%, respectively) norepinephrine-induced contractions, while higher concentrations (50 or 100 microg.mL-1) have not changed responses to norepinephrine. CONCLUSIONS Ropivacaine blocks neuronal norepinephrine reuptake by sympathetic nerve terminals.

Antinociceptive and anti-inflammatory effects of triterpenes from Pluchea quitoc DC. aerial parts

Background: Pluchea quitoc DC. (Asteraceae), a medicinal plant known as “quitoco,” “caculucage,” “tabacarana” and “madre-cravo,” is indicated for inflammatory conditions such as bronchitis, arthritis, and inflammation in the uterus and digestive system. Objective: This study evaluated the analgesic and anti-inflammatory activities of the triterpenes compounds obtained from P. quitoc aerial parts. Materials and Methods: The triterpenes compounds β-amyrin, taraxasterol and pseudo-taraxasterol in a mixture (T); β-amyrin, taraxasterol and pseudo-taraxasterol acetates in a mixture (Ta); β-amyrin, taraxasterol, pseudo-taraxasterol acetates in a mixture with β-amyrin, taraxasterol and pseudo-taraxasterol myristates (Tafe) were analyzed in the models of nociception and inflammation. The evaluation of antinociceptive activity was carried out by the acetic acid-induced writhing and tail-flick tests while leukocyte migration to the peritoneal cavity was used for anti-inflammatory profile. Results: The oral administration of T or Tafe (40 mg/kg and 70 mg/kg) and Ta (70 mg/kg) to mice reduced acetic acid-induced writhing. The tail-flick response of mice was not affected by T or Tafe (40 mg/kg). T or Tafe (40 mg/kg) and Ta (70 mg/kg) also inhibited peritoneal leukocyte infiltration following the injection of carrageenan. Conclusion: The results demonstrate the anti-inflammatory and peripheral antinociceptive activity of the triterpenes β-amyrin, taraxasterol, and pseudo-taraxasterol that were decreased when these were acetylated; while the acetylated triterpenes in mixture with myristyloxy triterpenes improved this activity. These compounds seem, at least in part, to be related to the plants reported activity.

Molecular studies with Aedes (Stegomyia) aegypti (Linnaeus, 1762), mosquito transmitting the dengue virus

Dengue is an infectious viral disease, which can present a wide clinical picture, ranging from oligo or asymptomatic forms, to bleeding and shock, and can progress to death. The disease problem has increased in recent years, especially in urban and suburban areas of tropical and subtropical regions. There are five dengue viruses, called serotypes (DEN-1, DEN-2, DEN-3, DEN-4, and DEN-5), which belong to the Flaviviridae family and are transmitted to humans through infected mosquito bites, with the main vector the Aedes aegypti mosquito (Linnaeus, 1762). Studies performed with Ae. aegypti, aimed at their identification and analysis of their population structure, are fundamental to improve understanding of the epidemiology of dengue, as well for the definition of strategic actions that reduce the transmission of this disease. Therefore, considering the importance of such research to the development of programs to combat dengue, the present review considers the techniques used for the molecular identification, and evaluation of the genetic variability of Ae. aegypti.