Is the injection of tramadol effective at control of pain after impacted mandibular third molar extractions? A systematic review and meta-analysis.

BACKGROUND: Third molar extraction is among the most common surgical procedures performed by oral-maxillofacial surgeons. Postoperative pain, swelling and trismus are common, especially in wisdom teeth, due to trauma to local tissues and the duration of the surgical procedure, among other factors. MATERIAL AND METHODS: This systematic review was conducted in accordance with the 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' in order to answer the focused question: 'Is the local submucosal injection of tramadol effective at the control of postoperative pain in patients submitted to impacted mandibular third molar extractions?'. We analyzed papers published until March 30, 2021 in the MEDLINE|PubMed, Web of Science and Cochrane Library databases. Gray literature was also consulted. Standard pairwise meta-analyses of direct comparisons were performed using a fixed-effect model; I2 ≥ 50 % or ≥ 75 % indicated moderate or high heterogeneity, respectively. Risk of bias was assessed by Cochrane Collaboration's tool. RESULTS: In total, 172 participants (98 males and 74 females, aged 18 or over) from three randomized placebo-controlled trials were considered for analysis. The submucosal injection of 2 ml of tramadol adjacent to the impacted mandibular third molar was effective in controlling pain up to 6-hours after surgery, in increasing the onset of consumption of rescue analgesic and in reducing the total number of rescue analgesics used. CONCLUSIONS: The submucosal injection of tramadol can be considered a safe and effective procedure for pain control after impacted mandibular third molar extractions.

Free gossypol supplementation frequency and reproductive toxicity in young bulls.

The aim of the present study was to analyze seminal quality of young bulls subjected to different frequencies of gossypol supplementation. Forty-eight Nellore bulls, with 19 months of age and weighing 357.8 ±â€¯7.2 kg, were used in this study. Animals were fed with 10.5 kg of standard supplement containing free-gossypol from whole cottonseed (WCS) at the following frequency: 3x/week (G3x), 5x/week (G5x) or 7x/week (G7x - Control). Additionally, a negative control was provided, and the treated animals received only mineral supplement (MM) ad libtum. The experiment lasted for 84 days and semen was collected at the beginning and at the end for analysis and cryopreservation. Fresh semen was used for initial analysis and plasma membrane integrity and sperm morphology were also determined. General motility using computer assisted sperm analysis (CASA), plasma and acrosomal membranes integrity, mitochondrial activity, and induced oxidative stress were assessed in post-thawed semen. The study design was completely randomized. Parametric data were analyzed by ANOVA and non-parametric data by the Wilcoxon test, using the statistical program SAS. Level of significance was set at 5%. Supplementation with WCS, regardless the frequency, increased total (P = .009) and head (P = .005) defects in comparison to animals receiving only forage and mineral supplement. Infrequent supplementation, particularly 5 times in the week (G5X), increased head (P = .026) and midpiece (P = .014) abnormalities. Sperm motility in fresh semen was lower in animals that received daily supplementation than those supplemented on alternate days (P = .021). Additionally, animals supplemented daily showed lower percentage of spermatozoa with intact acrosome compared to those supplemented on alternate days (P = .005). Thus, regardless the frequency of supplementation, free-gossypol supplementation affects sperm quality. Although the amount of free gossypol supplied weekly was the same among treatments, daily supplementation compromised sperm kinetics, differently from infrequent supplementation that led to sperm defects developed during spermatogenesis.

Dynamic structure of NGF and proNGF complexed with p75NTR: pro-peptide effect.

Crystallographic structures of NGF/p75NTR and proNGF/p75NTR were previously obtained in 2:1 and 2:2 stoichiometries, respectively. However, evidence shows that both stoichiometries can occur for mature neurotrophins and pro-neurotrophins. We used Molecular Dynamics (MD) simulations to examine the energetic and structural characteristics of these two complete systems as well as the uncomplexed forms of NGF and understand how these could translate in a new view of different biological outcomes. Here, we show that one chain at the 2:2 proNGF complex seems to be preferentially lost creating a 2:1 structure able to interact with sortilin. We also demonstrated that the structure of the neurotrophin dimers is not pre-established and suffers large structural modifications upon p75NTR binding. Moreover, our data suggests an elegant explanation for the dual role of NGF in neuronal cell death and survival, where different stoichiometries induce conformational changes that might be the basis for the different biological outcomes observed with the mature and proforms of neurotrophins.

Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways.

Neurotrophins protect neurons against glutamate excitotoxicity, but the signaling mechanisms have not been fully elucidated. We studied the role of the phosphatidylinositol 3-kinase (PI3-K) and Ras/mitogen-activated protein kinase (MAPK) pathways in the protection of cultured hippocampal neurons from glutamate induced apoptotic cell death, characterized by nuclear condensation and activation of caspase-3-like enzymes. Pre-incubation with the neurotrophin brain-derived neurotrophic factor (BDNF), for 24 h, reduced glutamate-evoked apoptotic morphology and caspase-3-like activity, and transiently increased the activity of the PI3-K and of the Ras/MAPK pathways. Inhibition of the PI3-K and of the Ras/MAPK signaling pathways abrogated the protective effect of BDNF against glutamate-induced neuronal death and similar effects were observed upon inhibition of protein synthesis. Moreover, incubation of hippocampal neurons with BDNF, for 24 h, increased Bcl-2 protein levels. The results indicate that the protective effect of BDNF in hippocampal neurons against glutamate toxicity is mediated by the PI3-K and the Ras/MAPK signaling pathways, and involves a long-term change in protein synthesis.

Going down to the local: incorporating social organisation and political culture into assessments of decentralised health care.

The social organisation and political culture of the society in which an organisation is embedded can have major effects on the way in which organisational policy is implemented and on how that organisation functions. Research on health sector reforms has paid scant attention to this aspect. If the claims made for decentralised management in the health sector are to be evaluated seriously, it is critical to develop concepts and methods to evaluate not only the formal organisation and the outputs of the health system, but also the aspects of local social organisation and political culture within which that local health system is embedded that may mediate their relationship. The paper explores three cases of district health systems in Northeast Brazil in order to identify aspects of local social organisation and political culture that appear to influence the implementation of the reforms and thereby potentially impact upon the quality of the care provided. The results of the study indicate the importance that aspects of local social organisation and political culture may exert on the operations of a decentralised health system. Key aspects identified are: the space for autonomy; the space for local voice in political life; personalized and institutionalised influences on autonomy and local voice; differences of involvement of health staff with the district; different spaces of acceptable practice and accountability. These factors are seen to moderate the intent of the health reforms at all stages in their implementation. Three possibilities are discussed for the nature of the interaction in terms of cause and effect between the formal organisation of the health system and its local context. Seeing this relationship as one of a dialogue offers some cautious optimism for the potential of the reform agenda. The paper closes with suggestions on how to take this line of research forward.