Clinical efficacy of new α-bisabolol mouthwashes in postoperative complications of maxillofacial surgeries: a randomized, controlled, triple-blind clinical trial.

OBJECTIVES: The present study aimed to evaluate the efficacy of α-bisabolol (BISA)-based mouthwashes in the oral hygiene of patients submitted to oral and maxillofacial surgery. MATERIALS AND METHODS: A randomized, controlled, triple-blind clinical trial was conducted with 30 patients, undergoing oral and maxillofacial surgery. Three types of mouthwashes were developed, based at 0.12% chlorhexidine, 0.5% BISA, and 0.12% chlorhexidine + 0.5% BISA. The patients were evaluated in the preoperative and postoperative period, divided into three groups according to the mouthwash to be used. In the postoperative period, the oral hygiene quality of the patients was evaluated through the simplified oral hygiene index; the healing of the wounds was evaluated observing the presence of suture dehiscence and/or infection, and the pain was established using the Visual Analogue Scale. The antiseptic effect of the mouthwashes was evaluated in vitro. RESULTS: There were no differences in the efficacy of BISA-containing mouthwashes for oral hygiene, healing, and pain, compared to chlorhexidine based at 0.12%. There were no differences in the antiseptic activity of chlorhexidine and chlorhexidine + α-bisabolol-based mouthwashes. CONCLUSION: The results indicate that BISA-based mouthwashes have clinical efficacy, in the improvement of oral hygiene and wound healing, as well as in the reduction of postoperative pain. CLINICAL RELEVANCE: Considering that BISA has analgesic, antimicrobial, and anti-inflammatory properties, it is relevant to evaluate the efficacy of BISA-based mouthwashes in the oral hygiene of patients undergoing oral and maxillofacial surgery, seeking a better postoperative recovery.

The elav gene product of Drosophila, required in neurons, has three RNP consensus motifs.

A sequence of developmental events transforms neurons from their immature state to their mature, terminally differentiated state. The elav locus is one of the first examples of a gene that is expressed in neurons early during this developmental sequence. This gene has been shown to be required for the proper development of young neurons and for the maintenance of mature neurons. DNA sequence data presented in this report suggest that the elav gene product is an RNA binding protein, based on the presence of RNP (ribonucleoprotein) consensus sequences. This leads to the proposal that this protein is involved in the RNA metabolism of neurons.

(-)-α-Bisabolol reduces nociception and trigeminal central sensitisation in acute orofacial neuropathic pain induced by infraorbital nerve injury.

Neuropathic orofacial pain conditions represent a challenge to diagnose and treat. Natural substances are promising therapeutic options for the control of pain. AIMS: This study aimed to examine whether (-)-α-bisabolol (BISA), a natural terpene, can attenuate nociceptive behaviour and central sensitisation in a rodent model of trigeminal neuropathic pain. MATERIALS AND METHODS: Infraorbital nerve transection (IONX) or sham operation was performed in adult male rats. Head withdrawal thresholds as a measure of facial mechanical sensitivity were tested with von Frey monofilaments applied bilaterally to the facial vibrissal pad pre-operatively (baseline) and then post-operatively before and at 60, 120, 240 and 360 min after administration of vehicle control per oris (p.o.) or BISA (200 mg/kg p.o.) (n = 8/group). Effects of BISA or vehicle on the activity of nociceptive neurons recorded in the medullary dorsal horn (MDH) were tested on post - operative day 8-10. ANOVA followed by post-hoc Bonferroni tested for statistically significant differences (p < 0.05) across study groups and time points. KEY FINDINGS: IONX animals (but not sham or naïve animals) showed post-operative facial mechanical hypersensitivity that was unaffected by vehicle. However, administration of BISA at post-operative day 7 significantly reversed the mechanical hypersensitivity in IONX rats; this effect lasted for at least 6 h. BISA also attenuated IONX-induced central sensitisation of MDH nociceptive neurons, as reflected in reversal of their reduced activation thresholds, increased responses to graded mechanical stimuli and enhanced spontaneous activity. SIGNIFICANCE: BISA may attenuate nociceptive behaviour and central sensitisation in a rat model of acute trigeminal neuropathic pain.

Gastroprotective and anti-inflammatory activities integrated to chemical composition of Myracrodruon urundeuva Allemão - A conservationist proposal for the species.

ETHNOPHARMACOLOGICAL RELEVANCE: Myracrodruon urundeuva Allemão (Aroeira-do-Sertão), Anacardiaceae, is one of the most used plants in folk medicine in Northeastern Brazil as an anti-inflammatory, healing and antiulcer. This species is threatened with extinction due to anthropogenic exploitation. The importance of this study is to demonstrate the feasibility of a conservationist model of replacement of the M. urundeuva adult tree (inner bark) for its under developing plants (shoots) in order to ensure the preservation of this species, but also to ensure sufficient raw material for pharmaceutical purposes. AIM OF THE STUDY: To characterize chemically and assess the gastroprotective and anti-inflammatory activities of the fluid extracts from M. urundeuva innebark (adult plant) as well as stem and leaves of shoots (young plant). MATERIALS AND METHODS: The fluid extracts were prepared by maceration-percolation with hydroalcoholic solution according to the methodology described in the Brazilian Pharmacopoeia. These extracts were cleaned-up through solid phase extraction (SPE) and chemically characterized by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-ESI-QTOF MS/MS). Gastroprotective and anti-inflammatory activities of the extracts (700 or 1000 mg/kg) were assessed on ethanol-induced gastric lesions and Croton oil-induced ear edema in rats, respectively. The extracts were evaluated for cytotoxicity in vitro. RESULTS: The UPLC-ESI-QTOF-MS/MS analysis evidenced the presence of chalcones, flavonoids and tannins. Gastroprotective and anti-inflammatory activities achieved with fluid extracts from the stems and leaves was similar to inner bark. The fluid extracts were not toxic. CONCLUSION: It is possible to replace the inner bark of the adult tree for the stems and leaves from the shoots as raw material to be used in the preparation of its the phytotherapeutics. Therefore, this finding may help in the implementation of public policies that ensure the conservation of the species along with its sustainable use for pharmaceutical purposes.

Human dirofilariasis in the eyelid caused by Dirofilaria repens: An imported case. / Dirofilariasis palpebral causada por Dirofilaria repens: un caso importado.

CLINICAL CASE: The case concerns a 33-year-old Ukrainian woman, who came to the Ophthalmology Emergency Service, stating that she had a «worm¼ under the skin of her upper left eyelid that wriggled at night and bit her. A complete examination revealed a subcutaneous foreign body, which showed a filarial appearance and seemed to crawl under the skin. It was surgically removed to discover a live parasite, PCR-identified as Dirofilaria repens. DISCUSSION: Humans are accidental hosts in the cycle of Dirofilaria. There are only 8 reported cases of subcutaneous infection in Spain. Due to global warming, D. repens has become an emerging infectious agent in Central Europe countries such as Ukraine. The findings in this case are discussed.

The tamas gene, identified as a mutation that disrupts larval behavior in Drosophila melanogaster, codes for the mitochondrial DNA polymerase catalytic subunit (DNApol-gamma125).

From a screen of pupal lethal lines of Drosophila melanogaster we identified a mutant strain that displayed a reproducible reduction in the larval response to light. Moreover, this mutant strain showed defects in the development of the adult visual system and failure to undergo behavioral changes characteristic of the wandering stage. The foraging third instar larvae remained in the food substrate for a prolonged period and died at or just before pupariation. Using a new assay for individual larval photobehavior we determined that the lack of response to light in these mutants was due to a primary deficit in locomotion. The mutation responsible for these phenotypes was mapped to the lethal complementation group l(2)34Dc, which we renamed tamas (translated from Sanskrit as "dark inertia"). Sequencing of mutant alleles demonstrated that tamas codes for the mitochondrial DNA polymerase catalytic subunit (DNApol-gamma125).

Cloning, genomic organization and expression pattern of a novel Drosophila gene, the disco-interacting protein 2 (dip2), and its murine homolog.

We report the cloning and initial characterization of a novel gene encoding the Disco interacting protein 2 (Dip2). dip2 DNA complementary to RNA (cDNA) showed a high degree of sequence similarity to cDNAs of unknown function previously identified in humans and Caenorhabditis elegans. We have cloned the mouse homolog of the dip2 cDNA and characterized the expression of this gene by Northern blotting analysis and in situ hybridization to whole mount embryos. Our observations demonstrate that there is a remarkable degree of sequence conservation at the dip2 locus that is reflected in the nervous system-specific expression of both the Drosophila and mouse homologs.

Effects of acute and repeated dose administration of caffeine and pentoxifylline on diazepam-induced mouse behavior in the hole-board test.

RATIONALE: The behavioral effects of methyl xanthines and their interactions with benzodiazepines have not been clearly established in animal models of anxiety. OBJECTIVE: The present study extended the previous studies to determine the effects of acute and repeated administration of caffeine, a non-specific phosphodiesterase (PDE) inhibitor and pentoxyfylline, a specific type-4 phosphodiesterase (PDE4) inhibitor on (1) baseline anxiety-like behavior and (2) the response to an acute challenge with diazepam on anxiety-like behavior in the hole-board test. METHODS: Mice were observed for the number of head-dips they made into the holes of the hole-board apparatus during a 5-min period, starting 30 min after acute (20 mg/kg) and repeated oral dose (20 mg/kg, twice a day for 4 days) administration of caffeine and pentoxifylline. In separate experiments, the response to an acute challenge with graded doses of diazepam (0.375 3 mg/kg, SC) was observed in naive mice or mice on acute and repeated dose regimen with methyl xanthines. RESULTS: Mice on acute but not after repeated dose regimen demonstrated a significantly increased number of hole-dips, indicating an anxiolytic-like effect of methylxanthines. Diazepam at the lower doses (0.375 and 0.75 mg/kg) but not at the highest doses (1.5 and 3 mg/kg) examined produced a significant anxiolytic-like effect. After an acute dose exposure of mice to caffeine and pentoxifylline, a rightward shift in the dose-response curve of diazepam was observed and particularly at 1.5 mg/kg dose, the net effect of diazepam was significantly enhanced which was, however, impaired upon repeated administration, more so with caffeine than with pentoxifylline. CONCLUSIONS: It is concluded that the xanthine drugs exert anxiolytic-like activity similar to diazepam in the hole-board test. In addition, they seem to modulate the anxiolytic effects of diazepam after both acute and repeated administration, probably as a result of an endogenous adenosinergic mechanism which may have therapeutic significance.

Human schistosomiasis: Schistosoma mansoni antigen detection in renal glomeruli.

Twelve kidney, five biopsy and seven necropsy specimens, all from schistosomiasis mansoni patients were studied by light and immunoflurescent microscopy in an attempt to detect antigen in the glomerular walls. Deposits of IgM, IgG,I gA, IgE, complement C3 and fibrinogen were observered in most cases. Antigen was successfully detected in two cases(one biopsy and one necropsy specimen), both exhibiting proliferative glomerulonephritis. The only clinical manifestation was a slight proteinuria. IgG antibodies eluted from the sutopsy kidney homogenates showed specific binding mostly to Schistosoma mansoni gut, thus spggesting that the fixed antibodies (eluates) are, at least partially, consituted by antibodies similar to the anti-circulating antigen. These data reinfroce the hypothesis that renal injury in schistosomiasis is mediated through an immune complex disease.

Attenuation of ischemia/reperfusion-induced intestinal injury by oleo-resin from Copaifera langsdorffii in rats.

Copaifera langsdorffii oleo-resin (CLOR) is a reputed herbal medicine used to combat gastrointestinal functional disorders. Our previous studies show that CLOR prevents gastric ulceration and promotes wound healing. This study examined the effects of CLOR on intestinal damage associated with mesenteric ischemia/reperfusion in rat. Wistar albino rats were divided into four groups of six in each. Group 1: Sham operated, Group 2: Vehicle + 45 min of ischemia followed by 60 min reperfusion (I/R), Groups 3 and 4: I/R + CLOR (200 and 400 mg /kg, p.o., respectively). All treatments were given 24 h, 12 h and 2 h before I/R. Animals were sacrificed at the end of reperfusion period and ileal tissue samples were obtained for biochemical analysis. Myeloperoxidase (MPO), an index of polymorphonuclear leukocytes; malondialdehyde (MDA), an end product of lipoperoxidation; catalase (CAT), an antioxidant enzyme; reduced glutathione (GSH), a key antioxidant; and nitrite, a marker of nitric oxide (NO) production were determined in ileum homogenates. The results show that I/R produces a significant increase in MDA content, MPO, and CAT activities with a significant decrease in GSH and an elevation in nitrite production, as compared to sham control. CLOR treatment caused significant attenuations in I/R-associated increases of MPO, MDA and CAT activities and on nitrite level. Besides, CLOR could effectively prevent the I/R-associated depletion of GSH. The data indicate that the oleo-resin has a protective action against I/R-induced intestinal tissue damage, which appeared to be, at least in part, due to an antioxidant and anti-lipid peroxidation mechanism.

Mexican use of lead in the treatment of empacho: community, clinic, and longitudinal patterns.

This paper discusses research designed to investigate community, clinic, and longitudinal patterns in use of lead as a treatment for empacho, a folk illness manifest by gastrointestinal symptoms. The same questionnaire used in a clinic-based study seven years previously in Guadalajara, Mexico, was used to interview a randomly selected community sample: in addition, the study was repeated at the same clinic sites that had been studied previously. The goals were to investigate: (1) What are community wide prevalences of empacho and use of lead based remedies? (2) To what extent are current patterns of use of lead for treatment of empacho in clinic-based samples similar to those seven years ago. The attributable risk to the population as a whole from use of lead based remedies was found to be 11% of the households of Guadalajara. Essentially this same estimate was seen for the 1987 and 1994 clinic populations. Interestingly, while percentages of lead users have declined since 1987, twice as great a percentage of informants reported treating empacho. Other patterns originally identified in 1987 persisted in 1994; lead use continues to be associated with lower levels of parental education and income.

1,8-cineole (eucalyptol), a monoterpene oxide attenuates the colonic damage in rats on acute TNBS-colitis.

The monoterpene oxide, 1,8-cineole (cineole, eucalyptol) was examined for its possible influence on the acute phase of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. The test compound, 1,8-cineole (200 and 400 mg/kg) or vehicle (1 ml, 2% Tween 80) was instilled rectally, 24, and 2 h before (pre-treatment) or 2 and 24 h after (post-treatment) the induction of colitis by intracolonic administration of TNBS (0.25 ml of 25 mg of TNBS in 50% ethanol). Rats were killed 48 h after colitis induction and colonic segments were analysed for gross damage scores, changes in wet weights, myeloperoxidase activity, an indicator of neutrophilic infiltration and glutathione level, a major cellular antioxidant. TNBS induced an extensive inflammation and ulceration in the colon. Colonic damage was associated with an increase in myeloperoxidase activity and by a decrease in glutathione. When compared to vehicle-treated TNBS controls, a marked reduction in gross damage scores and wet weights (mg/cm) of colonic segments were evident in animals pre-treated but not post-treated with 1,8-cineole. Cineole also significantly reduced the myeloperoxidase activity, and caused repletion of glutathione. These results confirm the anti-inflammatory action of 1,8-cineole and suggest its potential value as a dietary flavoring agent in the prevention of gastrointestinal inflammation and ulceration.

Investigations on the antinociceptive activity of crude extracts from Croton cajucara leaves in mice.

The crude leaf extracts of Croton cajucara Benth. were studied for their antinociceptive property in chemical and thermal models of nociception in mice. All the tested extracts (hexanic, chloroformic and methanolic), at oral doses of 100 and 200 mg/kg demonstrated significant inhibition of acetic acid-induced writhing and the second phase response of formalin, but did not manifest a significant effect in hot-plate test.

Silencing synaptic communication between random interneurons during Drosophila larval locomotion.

Genetic manipulation of individual neurons provides a powerful approach toward understanding their contribution to stereotypic behaviors. We describe and evaluate a method for identifying candidate interneurons and associated neuropile compartments that mediate Drosophila larval locomotion. We created Drosophila larvae that express green fluorescent protein (GFP) and a shibire(ts1) (shi(ts1)) transgene (a temperature-sensitive neuronal silencer) in small numbers of randomly selected cholinergic neurons. These larvae were screened for aberrant behavior at an elevated temperature (31-32°C). Among larvae with abnormal locomotion or sensory-motor responses, some had very small numbers of GFP-labeled temperature-sensitive interneurons. Labeled ascending interneurons projecting from the abdominal ganglia to specific brain neuropile compartments emerged as candidates for mediation of larval locomotion. Random targeting of small sets of neurons for functional evaluation, together with anatomical mapping of their processes, provides a tool for identifying the regions of the central nervous system that are required for normal locomotion. We discuss the limitations and advantages of this approach to discovery of interneurons that regulate motor behavior.

Bisabolol-induced gastroprotection against acute gastric lesions: role of prostaglandins, nitric oxide, and KATP+ channels.

The effects of Matricaria recutita and alpha-bisabolol, a bioactive component from Chamomile species, were investigated against gastric damage induced by absolute ethanol (96%, 1 mL per animal) in rats. The effects of M. recutita extract and alpha-bisabolol on gastric mucosal damage were assessed by determination of changes in mean gastric lesion area. Mechanistic studies were carried out at with 100 mg=kg alpha-bisabolol. We further examined the possible participation of prostaglandins, nitric oxide, and KATP+ channels in its mechanism. M. recutita reduced gastric damage in all doses tested. Alpha-bisabolol at oral doses of 50 and 100 mg=kg markedly attenuated the gastric lesions induced by ethanol to the extent of 87% and 96%, respectively. Pretreatments with the nitric oxide antagonist N-nitro-l-arginine methyl ester (10 mg=kg, i.p.) or with indomethacin, an inhibitor of cyclooxygenase, failed to block effectively the gastroprotective effect of alpha-bisabolol. Furthermore, the alpha-bisabolol effect was significantly reduced in rats pretreated with glibenclamide, an inhibitor of KATP+ channel activation. Thus we provide evidence that alpha-bisabolol reduces the gastric damage induced by ethanol, at least in part, by the mechanism of activation of KATP+ channels.

Relaxant effects of an alkaloid-rich fraction from Aspidosperma ulei root bark on isolated rabbit corpus cavernosum.

We described earlier that an alkaloid-rich fraction (F(3-5)) from Aspidosperma ulei (Markgr) induces penile erection-like behavioral responses in mice. This study verified a possible relaxant effect of this fraction on isolated rabbit corpus cavernosum (RbCC) strips precontracted by phenylephrine (1 microM) or K+ 60 mM. F(3-5) (1-300 microg ml(-1)) relaxed the RbCC strips in a concentration-dependent and reversible manner. The relaxant effect of F(3-5) (100 microg ml(-1)) on phenylephrine contraction was unaffected in the presence of atropine, N-omega-nitro-L-arginine methyl ester or 1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one and by preincubation with tetrodotoxin, glibenclamide, apamine and charybdotoxin suggesting that mechanisms other than cholinergic, nitrergic, sGC activation or potassium channel opening are probably involved. However, the phasic component of the contraction induced by K+ 60 mM as well as the maximal contraction elicited by increasing external Ca2+ concentrations in depolarized corpora cavernosa was inhibited by F(3-5). We conclude that F(3-5) relaxes the RbCC smooth muscle, at least in part, through a blockade of calcium influx or its function.

Acute effects of guarana (Paullinia cupana Mart.) on mouse behaviour in forced swimming and open field tests.

Guarana, a herbal extract from the seeds of Paullinia cupana Mart. has been evaluated in comparison with caffeine on mouse behaviour in forced swimming and open field tests. Guarana (25 and 50 mg/kg, p.o.) and caffeine (10 and 20 mg/kg, p.o.) each significantly reduced the duration of immobility in the forced swimming test suggesting an antidepressant-like effect in mice. At these doses, neither substance affected ambulation in the open field test. However, a high dose of guarana (100 mg/kg) and caffeine (30 mg/kg) significantly enhanced the locomotor activity in the open field test. Caffeine, but not guarana, could effectively block an adenosine agonist, cyclopentyl adenosine (CPA)-induced increase in swimming immobility suggesting that mechanism(s) other than the adenosinergic mechanism are involved in the antidepressant-like activity of guarana.

The larval optic nerve is required for the development of an identified serotonergic arborization in Drosophila melanogaster.

The larval visual system in the fruitfly Drosophila melanogaster consists of two bilateral clusters of 12 photoreceptor cells. These neurons send their axons in a fascicle, the Bolwig's nerve, toward the target area in the ventral lateral region of the brain hemispheres. We describe the development of a serotonergic arborization originating in the central brain found in the larval optic center in association with the larval optic nerve. This arborization is formed by processes from larval neurons born during embryogenesis. However, these neuronal processes do not reach their final destination, the larval optic center, until late in larval development. Using mutations that disrupt the connectivity and/or development of the larval photoreceptor cells, as well as mosaic analysis, we demonstrate that the innervation of the larval optic center by this serotonergic arborization depends upon contact with the larval optic nerve.

Mutant alleles at the locus elav in Drosophila melanogaster lead to nervous system defects. A developmental-genetic analysis.

We report a developmental and genetic analysis of the X-linked vital locus l(1)EC7 in Drosophila melanogaster. The locus maps in the salivary band region 1B4-5 to 1B8-9, a part of the X chromosome previously shown to be essential for normal neural development. Certain mutant alleles at the locus can cause embryonic lethality, indicating that the function provided by the gene is essential during embryogenesis. A developmental analysis of gynandromorphic genetic mosaics shows that: (1) the gene function is autonomously essential in the eye; (2) the gene function is essential for normal development of the optic lobes; and (3) the gene function is not necessary in most major imaginal-disc cell derivatives with the exception of the eye disc. Conclusions from the developmental analysis of a temperature sensitive allele are consistent with those from the mosaic analysis. The embryonic lethality caused by the mutant alleles and abnormalities observed in the genetic mosaics have led us to rename the locus l(1)EC7 to elav (embryonic lethal, abnormal visual system).

Establishment of neuronal connectivity during development of the Drosophila larval visual system.

We used confocal microscopy in conjunction with specific antibodies and enhancer trap strains to investigate the development of specific neuronal connections in a simple model system, the larval visual system of Drosophila. We find that the establishment of axonal projections from the larval photoreceptor neurons to their central nervous system targets involves a series of discrete steps. During embryogenesis, the larval optic nerve contacts several different cell types, including optic lobe pioneer (OLP) neurons and a number of glial cells. We demonstrate that OLP neurons are present and project normally in glass (gl) mutant embryos in which the larval optic nerve fails to develop, suggesting that they do not depend on interactions with the larval optic nerve for differentiation and proper axonal projection. The OLPs fail to differentiate properly is disconnected (disco) mutant embryos, where appropriate connections between the larval optic nerve and its targets in the brain are not formed. The disco gene is expressed in the OLPs and may therefore act autonomously to direct the differentiation of these cells. Taken together, our results suggest that the OLPs act as an intermediate target required for the establishment of normal optic nerve projection and connectivity.