Intramuscular injection of dexamethasone for the control of pain, swelling, and trismus after third molar surgery: a systematic review and meta-analysis.

This systematic review aimed to answer the following PICO question: Does the intramuscular injection of dexamethasone result in less pain, swelling, and trismus after mandibular third molar removal when compared to other routes of administration or a control group (saline solution injection or no treatment)? An electronic search was conducted in Virtual Health Library, PubMed, and Web of Science, through March 2018. Eligibility criteria included clinical trials. The search strategy resulted in 331 studies. Following the selection process, 15 articles were included in the systematic review; eight of these were included in the meta-analysis. Most of the studies had an unclear risk of bias (Cochrane Handbook assessment). Pain (mean difference (MD) -1.58, 95% confidence interval (CI) -1.99 to -1.16) and oedema (MD -1.76, 95% CI -2.38 to -1.14) were lower in the intramuscular dexamethasone group when compared to the control group. When compared to the submucosal route, the intramuscular route was more effective only for pain on the third postoperative day (MD -0.79, 95% CI -1.38 to -0.20). The results suggest that the intramuscular injection of dexamethasone may be an alternative route of administration, since it is effective at reducing pain and oedema when compared to non-steroidal treatment and has similar results to the submucosal route.

Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.

3,4-methylenedioxymethamphetamine (MDMA--Ecstasy) decreases neutrophil activity through the glucocorticoid pathway and impairs host resistance to Listeria monocytogenes infection in mice.

Ecstasy is the popular name of the abuse drug 3,4-methylenedioxymethamphetamine (MDMA) that decreases immunity in animals. The mechanisms that generate such alterations are still controversial. Seven independent pharmacological approaches were performed in mice to identify the possible mechanisms underlying the decrease of neutrophil activity induced by MDMA and the possible effects of MDMA on host resistance to Listeria monocytogenes. Our data showed that MDMA (10 mg kg(-1)) administration decreases NFκB expression in circulating neutrophils. Metyrapone or RU-486 administration prior to MDMA treatment abrogated MDMA effects on neutrophil activity and NFκB expression, while 6-OHDA or ICI-118,551 administration did not. As MDMA treatment increased the plasmatic levels of adrenaline and noradrenaline, propranolol pre-treatment effects were also evaluated. Propranolol suppressed both MDMA-induced increase in corticosterone serum levels and its effects on neutrophil activity. In a L. monocytogenes experimental infection context, we showed that MDMA: induced myelosuppression by decreasing granulocyte-macrophage hematopoietic progenitors (CFU-GM) in the bone marrow but increased CFU-GM in the spleen; decreased circulating leukocytes and bone marrow cellularity and increased spleen cellularity; decreased pro-inflammatory cytokine (IL-12p70, TNF, IFN-γ, IL-6) and chemokine (MCP-1) production 24 h after the infection; increased the production of pro-inflammatory cytokines and chemokines 72 h after infection and decreased IL-10 levels at all time points analyzed. It was proposed that MDMA immunosuppressive effects on neutrophil activity and host resistance to L monocytogenes rely on NFκB signaling, being mediated by HPA axis activity and corticosterone.

Overcrowding stress decreases macrophage activity and increases Salmonella Enteritidis invasion in broiler chickens.

Overcrowding stress is a reality in the poultry industry. Chickens exposed to long-term stressful situations present a reduction of welfare and immunosuppression. We designed this experiment to analyse the effects from overcrowding stress of 16 birds/m(2) on performance parameters, serum corticosterone levels, the relative weight of the bursa of Fabricius, plasma IgA and IgG levels, intestinal integrity, macrophage activity and experimental Salmonella Enteritidis invasion. The results of this study indicate that overcrowding stress decreased performance parameters, induced enteritis and decreased macrophage activity and the relative bursa weight in broiler chickens. When the chickens were similarly stressed and infected with Salmonella Enteritidis, there was an increase in feed conversion and a decrease in plasma IgG levels in the stressed and Salmonella-infected birds. We observed moderate enteritis throughout the duodenum of chickens stressed and infected with Salmonella. The overcrowding stress decreased the macrophage phagocytosis intensity and increased Salmonella Enteritidis counts in the livers of birds challenged with the pathogenic bacterium. Overcrowding stress via the hypothalamic-pituitary-adrenal axis that is associated with an increase in corticosterone and enteritis might influence the quality of the intestinal immune barrier and the integrity of the small intestine. This effect allowed pathogenic bacteria to migrate through the intestinal mucosa, resulting in inflammatory infiltration and decreased nutrient absorption. The data strengthen the hypothesis that control of the welfare of chickens and avoidance of stress from overcrowding in poultry production are relevant factors for the maintenance of intestinal integrity, performance and decreased susceptibility to Salmonella infection.

Pre-emptive effect of dexamethasone and methylprednisolone on pain, swelling, and trismus after third molar surgery: a split-mouth randomized triple-blind clinical trial.

The aim of this study was to compare the effect of dexamethasone 8 mg and methylprednisolone 40 mg for the control of pain, swelling, and trismus following the extraction of impacted third molars. Sixteen healthy patients with a mean age of 20.3 (standard deviation 1.25) years received a single oral dose of either drug 1 h prior to each surgical procedure (left and right teeth). At 24, 48, and 72 h and 7 days following surgery, swelling was determined using linear measurements on the face and trismus was determined by maximal mouth opening. Postoperative pain was self-recorded by the patients using a visual analogue scale at 8-h intervals for a period of 72 h. Data analysis involved descriptive statistics and the Wilcoxon, and paired t tests (P < 0.05). Dexamethasone controlled swelling better than methylprednisolone at all postoperative evaluations (P < 0.02) and led to greater mouth opening 48 h after surgery (P = 0.029). No statistically significant difference was found between drugs with regard to pain. In conclusion, pre-emptive dexamethasone 8 mg demonstrated better control of swelling and limited mouth opening in comparison to methylprednisolone 40 mg, with no differences between drugs regarding pain control.

Heat stress impairs performance and induces intestinal inflammation in broiler chickens infected with Salmonella Enteritidis.

Stressful situations reduce the welfare, production indices and immune status of chickens. Salmonella spp. are a major zoonotic pathogens that annually cause over 1 billion infections worldwide. We therefore designed the current experiment to analyse the effects of 31±1°C heat stress (HS) (from 35 to 41 days) on performance parameters, Salmonella invasion and small intestine integrity in broiler chickens infected with Salmonella Enteritidis. We observed that HS decreased body weight gain and feed intake. However, feed conversion was only increased when HS was combined with Salmonella Enteritidis infection. In addition, we observed an increase in serum corticosterone levels in all of the birds that were subjected to HS, showing a hypothalamus-pituitary-adrenal axis activation. Furthermore, mild acute multifocal lymphoplasmacytic enteritis, characterized by foci of heterophil infiltration in the duodenum, jejunum and ileum, was observed in the HS group. In contrast, similar but more evident enteritis was noted in the heat-stressed and Salmonella-infected group. In this group, moderate enteritis was observed in all parts of the small intestine. Lastly, we observed an increase in Salmonella counts in the spleens of the stressed and Salmonella-infected chickens. The combination of HS and Salmonella Enteritidis infection may therefore disrupt the intestinal barrier, which would allow pathogenic bacteria to migrate through the intestinal mucosa to the spleen and generate an inflammatory infiltrate in the gut, decreasing performance parameters.

Acute heat stress impairs performance parameters and induces mild intestinal enteritis in broiler chickens: role of acute hypothalamic-pituitary-adrenal axis activation.

Studies on the environmental consequences of stress are relevant for economic and animal welfare reasons. We recently reported that long-term heat stressors (31 ± 1°C and 36 ± 1°C for 10 h/d) applied to broiler chickens (Gallus gallus domesticus) from d 35 to 42 of life increased serum corticosterone concentrations, decreased performance variables and the macrophage oxidative burst, and produced mild, multifocal acute enteritis. Being cognizant of the relevance of acute heat stress on tropical and subtropical poultry production, we designed the current experiment to analyze, from a neuroimmune perspective, the effects of an acute heat stress (31 ± 1°C for 10 h on d 35 of life) on serum corticosterone, performance variables, intestinal histology, and peritoneal macrophage activity in chickens. We demonstrated that the acute heat stress increased serum corticosterone concentrations and mortality and decreased food intake, BW gain, and feed conversion (P < 0.05). We did not find changes in the relative weights of the spleen, thymus, and bursa of Fabricius (P > 0.05). Increases in the basal and the Staphylococcus aureus-induced macrophage oxidative bursts and a decrease in the percentage of macrophages performing phagocytosis were also observed. Finally, mild, multifocal acute enteritis, characterized by the increased presence of lymphocytes and plasmocytes within the lamina propria of the jejunum, was also observed. We found that the stress-induced hypothalamic-pituitary-adrenal axis activation was responsible for the negative effects observed on chicken performance and immune function as well as for the changes in the intestinal mucosa. The data presented here corroborate with those presented in other studies in the field of neuroimmunomodulation and open new avenues for the improvement of broiler chicken welfare and production performance.

Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice

Anxiolytic and anxiogenic-like behavioral outcomes have been reported for methylenedioxymethamphetamine (MDMA or ecstasy) in rodents. In the present experiment, we attempted to identify behavioral, hormonal and neurochemical outcomes of MDMA treatment to clarify its effects on anxiety-related responses in 2-month-old Balb/c male mice (25-35 g; N = 7-10 mice/group). The behavioral tests used were open field, elevated plus maze, hole board, and defensive behavior against predator odor. Moreover, we also determined striatal dopamine and dopamine turnover, and serum corticosterone levels. MDMA was injected ip at 0.2, 1.0, 5.0, 8.0, 10, or 20 mg/kg. MDMA at 10 mg/kg induced the following significant (P < 0.05) effects: a) a dose-dependent increase in the distance traveled and in the time spent moving in the open field; b) decreased exploratory activity in the hole board as measured by number of head dips and time spent in head dipping; c) increased number of open arm entries and increased time spent in open arm exploration in the elevated plus maze; d) increased time spent away from an aversive stimulus and decreased number of risk assessments in an aversive odor chamber; e) increased serum corticosterone levels, and f) increased striatal dopamine level and turnover. Taken together, these data suggest an anxiogenic-like effect of acute MDMA treatment, despite the fact that behavioral anxiety expression was impaired in some of the behavioral tests used as a consequence of the motor stimulating effects of MDMA.

Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice.

Anxiolytic and anxiogenic-like behavioral outcomes have been reported for methylenedioxymethamphetamine (MDMA or ecstasy) in rodents. In the present experiment, we attempted to identify behavioral, hormonal and neurochemical outcomes of MDMA treatment to clarify its effects on anxiety-related responses in 2-month-old Balb/c male mice (25-35 g; N = 7-10 mice/group). The behavioral tests used were open field, elevated plus maze, hole board, and defensive behavior against predator odor. Moreover, we also determined striatal dopamine and dopamine turnover, and serum corticosterone levels. MDMA was injected ip at 0.2, 1.0, 5.0, 8.0, 10, or 20 mg/kg. MDMA at 10 mg/kg induced the following significant (P < 0.05) effects: a) a dose-dependent increase in the distance traveled and in the time spent moving in the open field; b) decreased exploratory activity in the hole board as measured by number of head dips and time spent in head dipping; c) increased number of open arm entries and increased time spent in open arm exploration in the elevated plus maze; d) increased time spent away from an aversive stimulus and decreased number of risk assessments in an aversive odor chamber; e) increased serum corticosterone levels, and f) increased striatal dopamine level and turnover. Taken together, these data suggest an anxiogenic-like effect of acute MDMA treatment, despite the fact that behavioral anxiety expression was impaired in some of the behavioral tests used as a consequence of the motor stimulating effects of MDMA.

Heat stress impairs performance parameters, induces intestinal injury, and decreases macrophage activity in broiler chickens.

Studies on environmental consequences of stress on animal production have grown substantially in the last few years for economic and animal welfare reasons. Physiological, hormonal, and immunological deficits as well as increases in animals' susceptibility to diseases have been reported after different stressors in broiler chickens. The aim of the current experiment is to describe the effects of 2 different heat stressors (31 +/- 1 and 36 +/- 1 degrees C/10 h per d) applied to broiler chickens from d 35 to 42 of life on the corticosterone serum levels, performance parameters, intestinal histology, and peritoneal macrophage activity, correlating and discussing the obtained data under a neuroimmune perspective. In our study, we demonstrated that heat stress (31 +/- 1 and 36 +/- 1 degrees C) increased the corticosterone serum levels and decreased BW gain and food intake. Only chickens submitted to 36 +/- 1 degrees C, however, presented a decrease in feed conversion and increased mortality. We also showed a decrease of bursa of Fabricius (31 +/- 1 and 36 +/- 1 degrees C), thymus (36 +/- 1 degrees C), and spleen (36 +/- 1 degrees C) relative weights and of macrophage basal (31 +/- 1 and 36 +/- 1 degrees C) and Staphylococcus aureus-induced oxidative burst (31 +/- 1 degrees C). Finally, mild multifocal acute enteritis characterized by an increased presence of lymphocytes and plasmocytes within the jejunum's lamina propria was also observed. The stress-induced hypothalamic-pituitary-adrenal axis activation was taken as responsible for the negative effects observed on the chickens' performance and immune function and also the changes of the intestinal mucosa. The present obtained data corroborate with others in the field of neuroimmunomodulation and open new avenues for the improvement of broiler chicken welfare and production performance.

Translocator protein (18 kDa) mediates the pro-growth effects of diazepam on Ehrlich tumor cells in vivo.

The Translocator Protein (TSPO), previously known as the peripheral-type benzodiazepine receptor, is a ubiquitous drug- and cholesterol-binding protein that is up regulated in several types of cancer cells. TSPO drug ligands (e.g., diazepam) induce or inhibit tumor cell proliferation, depending on the dose and tissue origin. We have previously shown that TSPO is expressed in Ehrlich tumor cells and that diazepam increases proliferation of these cells in vitro. Here, we investigated the in vivo effects of diazepam on Ehrlich tumor growth and the role of TSPO in mediating this process. Oral administration of diazepam to mice (3.0mg/kg/day for 7 days) produced plasma and ascitic fluid drug concentrations of 83.83 and 54.12 nM, respectively. Diazepam increased Ehrlich tumor growth, likely due to its ability to increase tumor cell proliferation and Reactive Oxygen Species production. Radioligand binding assays and nucleotide sequencing revealed that Ehrlich tumor cell TSPO had the same pharmacological and biochemical properties as TSPO described in other tumor cells. The estimated K(d) for PK 11195 in Ehrlich tumor cells was 0.44 nM and 8.70 nM (low and high binding site, respectively). Structurally diverse TSPO drug ligands with exclusive affinity for TSPO (i.e., 4-chlordiazepam, Ro5-4864, and isoquinoline-carboxamide PK 11195) also increased Ehrlich tumor growth. However, clonazepam, a GABA(A)-specific ligand with no affinity for TSPO, failed to do so. Taken together, these data suggest that diazepam induces in vivo Ehrlich tumor growth in a TSPO-dependent manner.

Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9 percent saline, ethyl alcohol, Emulphor® (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.

Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests.

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.

Anti-inflammatory and analgesic activities of the latex containing triterpenes from Himatanthus sucuuba.

Some triterpenes and iridoids were previously isolated from the stem bark of Himatanthus sucuuba. The latex from Himatanthus sucuuba is used in popular amazonian medicine as an anti-inflammatory remedy. Fractions of the latex were pharmacologically evaluated with a view to verify this popular use in the carrageenan-induced rat paw edema and in the acetic acid-induced mouse constriction tests. The hexane fraction inhibited the edema formation by 35.9% at a dose of 200 mg/kg (p.o.) but no activity was observed at 100 mg/kg (p.o.). The triterpenes present in the hexane fraction were identified as lupeol acetate, alpha-amyrin and lupeol cinnamates. The fraction containing only cinnamates inhibited the edema and the abdominal constrictions by 50-40% and 57.9%, respectively, at 100 mg/kg (p.o.). Among all the fractions studied, the fraction containing only cinnamates showed the greatest anti-inflammatory activity which suggests that these compounds were responsible for the previously described activity of the crude extract.

P300 results in patients with lesions of the auditory areas of the cerebrum.

Auditory P300 event-related potentials were obtained at C3 and C4 recording sites from 20 patients with cerebral lesions that affected auditory areas of the brain. The patient group was matched for age and hearing sensitivity to a control group of 20 subjects. There were significant differences between the two groups for both latency and amplitude of the P300. Eight patients demonstrated an absent P300 for at least one recording condition while all subjects in the control group had readable P300s in all recording conditions. A subset of patients with lesions limited to one hemisphere showed no laterality effects for amplitude or latency of the P300 for the ear or electrode that was either ipsilateral or contralateral to the lesion. In comparison to the P2 evoked potential, the P3 was more sensitive to neurologic lesions.

Duration pattern recognition in normal subjects and patients with cerebral and cochlear lesions.

Three groups of subjects were tested on a duration pattern recognition task. The groups included normal subjects, subjects with cochlear hearing loss, and subjects with lesions involving but not limited to the auditory areas of the cerebrum. Results indicated no significant difference in pattern recognition between the normal subjects and subjects with cochlear hearing loss. However, the subjects with cerebral lesions performed significantly more poorly than either the normal subjects or those with cochlear hearing loss. In comparing pattern recognition performance for the ears ipsilateral and contralateral to the lesioned hemispheres no differences were noted. Rather, when a central lesion was present, both ears generally yielded abnormal scores.

Frequency patterns in cochlear, brainstem, and cerebral lesions.

Three groups of patients with different pathologies (cerebral, brainstem, and cochlear lesions) were tested and compared for performance on frequency patterns. Results indicated that the frequency pattern test was highly sensitive to cerebral lesions (83%), but not as sensitive to brainstem lesions (45%). There was very little overlap between results of subjects with cochlear hearing loss and those with cerebral lesions. The specificity of frequency patterns for detecting cerebral lesions (the number of true negative results divided by the number of cochlear subjects) was 88.2%.

Auditory dysfunction following a gunshot wound of the pons.

A patient with a gunshot wound penetrating the right side of the brainstem at the level of the pons was given a test battery to evaluate peripheral hearing function and central auditory processing abilities. A month later, the left ear had a loss of sensitivity for high frequency tones, decreased speech discrimination, and excess tone decay. Two years later these deficits had resolved. However, a central auditory impairment remained, affecting the right ear score on Binaural Fusion and left ear scores on dichotic tasks and tonal pattern sequences.