Physical Exercise Promotes Beneficial Changes on Neurotrophic Factors in Mesolimbic Brain Areas After AMPH Relapse: Involvement of the Endogenous Opioid System.

Addiction is a serious public health problem, and the current pharmacotherapy is unable to prevent drug use reinstatement. Studies have focused on physical exercise as a promising coadjuvant treatment. Our research group recently showed beneficial neuroadaptations in the dopaminergic system related to amphetamine-relapse prevention involving physical exercise-induced endogenous opioid system activation (EXE-OS activation). In this context, additional mechanisms were explored to understand the exercise benefits on drug addiction. Male rats previously exposed to amphetamine (AMPH, 4.0 mg/kg) for 8 days were submitted to physical exercise for 5 weeks. EXE-OS activation was blocked by naloxone administration (0.3 mg/kg) 5 min before each physical exercise session. After the exercise protocol, the rats were re-exposed to AMPH for 3 days, and in sequence, euthanasia was performed and the VTA and NAc were dissected. In the VTA, our findings showed increased immunocontent of proBDNF, BDNF, and GDNF and decreased levels of AMPH-induced TrkB; therefore, EXE-OS activation increased all these markers and naloxone administration prevented this exercise-induced effect. In the NAc, the same molecular markers were also increased by AMPH and decreased by EXE-OS activation. In this study, we propose a close relation between EXE-OS activation beneficial influence and a consequent neuroadaptation on neurotrophins and dopaminergic system levels in the mesolimbic brain area, preventing the observed AMPH-relapse behavior. Our outcomes bring additional knowledge concerning addiction neurobiology understanding and show that EXE-OS activation may be a potential adjuvant tool in drug addiction therapy.

Comparative evaluation of displacement and stress distribution pattern during mandibular arch distalization with extra and inter-radicular mini-implants: a three-dimensional finite element study.

OBJECTIVE: To compare the initial stress distribution and displacement on mandibular dentition using extra and inter-radicular mini-implants for arch distalization, by means of finite element analysis. METHODS: For this study, two finite element models of the mandible were designed. The models consisted of periodontal ligament (PDL) and alveolar bone of all teeth until second molars. In the Case 1, bilateral extra-radicular buccal-shelf stainless steel mini-implants (10.0-mm length; 2.0-mm diameter) were placed between first and second permanent molars. In the Case 2, bilateral inter-radicular stainless steel mini-implants (10.0-mm length; 1.5-mm diameter) were placed between second premolar and first permanent molar. Power hook was attached between canine and first premolar at a fixed height of 8mm. In the two cases, 200g of distalization force was applied. ANSYS v. 12.1 software was used to analyze and compare von Mises stress and displacement in the mandibular dentition, PDL and bone. RESULTS: Higher stresses were observed in mandibular dentition with the inter-radicular implant system. The amount of von Mises stress was higher for cortical bone (85.66MPa) and cancellous bone (3.64MPa) in Case 2, in comparison to cortical bone (41.93MPa) and cancellous bone (3.43MPa) in Case 1. The amount of arch distalization was higher for mandible in Case 1 (0.028mm), in comparison to Case 2 (0.026mm). CONCLUSION: Both systems were clinically safe, but extra-radicular implants showed more effective and controlled distalization pattern, in comparison to inter-radicular implants, in Class III malocclusion treatment.

Evaluation of patients of vaccine side effects after the COVID-19 vaccine

SUMMARY OBJECTIVE: Postvaccine side effects were evaluated in patients presenting to our emergency department with complaints of vaccine side effects after taking COVID-19 vaccine, and new unknown side effects ranging from mild complaints to life-threatening risks, and frequency of all side effects were investigated. This study aimed to establish a scientific resource to identify the potential side effects of the vaccine. METHODS: Patients' demographic information, clinical characteristics, epicrisis reports, COVID-19 disease and vaccination histories, vital values, and blood values were examined. The SPSS 20.0 package program was used for statistical evaluation. p<0.05 was considered statistically significant. RESULTS: Notably, 13.1% of patients presenting to the emergency department started to have complaints after taking Sinovac vaccine, whereas 86.9% of them had complaints after taking BioNTech vaccine. Also, 36.9% of patients stated that they had COVID-19. All patients had a Glasgow coma scale score of 15 during admission. No patient was hospitalized, ventilator was not needed, and all patients were discharged. While the most common presenting complaint to the emergency department after vaccination was fatigue in 29.7%, the most common diagnoses after examination in the emergency department were myalgia in 32.1% and upper respiratory tract infection in 28.6%. CONCLUSION: Results and conclusions of our study will guide healthcare workers and patients on the side effects of COVID-19 vaccine.

Comparative evaluation of displacement and stress distribution pattern during mandibular arch distalization with extra and inter-radicular mini-implants: a three-dimensional finite element study

ABSTRACT Objective: To compare the initial stress distribution and displacement on mandibular dentition using extra and inter-radicular mini-implants for arch distalization, by means of finite element analysis. Methods: For this study, two finite element models of the mandible were designed. The models consisted of periodontal ligament (PDL) and alveolar bone of all teeth until second molars. In the Case 1, bilateral extra-radicular buccal-shelf stainless steel mini-implants (10.0-mm length; 2.0-mm diameter) were placed between first and second permanent molars. In the Case 2, bilateral inter-radicular stainless steel mini-implants (10.0-mm length; 1.5-mm diameter) were placed between second premolar and first permanent molar. Power hook was attached between canine and first premolar at a fixed height of 8mm. In the two cases, 200g of distalization force was applied. ANSYS v. 12.1 software was used to analyze and compare von Mises stress and displacement in the mandibular dentition, PDL and bone. Results: Higher stresses were observed in mandibular dentition with the inter-radicular implant system. The amount of von Mises stress was higher for cortical bone (85.66MPa) and cancellous bone (3.64MPa) in Case 2, in comparison to cortical bone (41.93MPa) and cancellous bone (3.43MPa) in Case 1. The amount of arch distalization was higher for mandible in Case 1 (0.028mm), in comparison to Case 2 (0.026mm). Conclusion: Both systems were clinically safe, but extra-radicular implants showed more effective and controlled distalization pattern, in comparison to inter-radicular implants, in Class III malocclusion treatment.

RESUMO Objetivo: Comparar a distribuição da tensão inicial e o deslocamento na dentição inferior usando mini-implantes extra e inter-radiculares para distalização da arcada, por meio da análise de elementos finitos. Métodos: Dois modelos de elementos finitos da mandíbula foram criados, os quais consistiram de ligamento periodontal (PDL) e osso alveolar de todos os dentes até os segundos molares. No Caso 1, mini-implantes extra-radiculares de aço inoxidável (10,0 mm de comprimento; 2,0 mm de diâmetro) foram colocados bilateralmente na buccal-shelf entre o primeiro e o segundo molares permanentes. No Caso 2, mini-implantes de aço inoxidável inter-radiculares (comprimento de 10,0 mm; diâmetro de 1,5 mm) foram colocados bilateralmente entre o segundo pré-molar e o primeiro molar permanentes. Um Power hook foi preso entre o canino e o primeiro pré-molar a uma altura fixa de 8mm. Nos dois casos, foi aplicada força de distalização de 200g. O software ANSYS v. 12.1 foi usado para analisar e comparar a tensão de von Mises e o deslocamento na dentição inferior, ligamento periodontal e osso. Resultados: Maiores tensões foram observadas na dentição inferior com o sistema de implantes inter-radiculares. A quantidade de tensões de von Mises foi maior para osso cortical (85,66MPa) e osso esponjoso (3,64MPa) no Caso 2, em comparação com osso cortical (41,93MPa) e osso esponjoso (3,43MPa) no Caso 1. A quantidade de distalização da arcada inferior foi maior no Caso 1 (0,028 mm), em comparação com o Caso 2 (0,026 mm). Conclusão: Ambos os sistemas foram clinicamente seguros, mas os implantes extra-radiculares mostraram um padrão de distalização mais eficaz e controlado, em comparação com os implantes inter-radiculares, para tratamento da má oclusão de Classe III.

Dynamical modeling of miR-34a, miR-449a, and miR-16 reveals numerous DDR signaling pathways regulating senescence, autophagy, and apoptosis in HeLa cells.

Transfection of tumor suppressor miRNAs such as miR-34a, miR-449a, and miR-16 with DNA damage can regulate apoptosis and senescence in cancer cells. miR-16 has been shown to influence autophagy in cervical cancer. However, the function of miR-34a and miR-449a in autophagy remains unknown. The functional and persistent G1/S checkpoint signaling pathways in HeLa cells via these three miRNAs, either synergistically or separately, remain a mystery. As a result, we present a synthetic Boolean network of the functional G1/S checkpoint regulation, illustrating the regulatory effects of these three miRNAs. To our knowledge, this is the first synthetic Boolean network that demonstrates the advanced role of these miRNAs in cervical cancer signaling pathways reliant on or independent of p53, such as MAPK or AMPK. We compared our estimated probability to the experimental data and found reasonable agreement. Our findings indicate that miR-34a or miR-16 may control senescence, autophagy, apoptosis, and the functional G1/S checkpoint. Additionally, miR-449a can regulate just senescence and apoptosis on an individual basis. MiR-449a can coordinate autophagy in HeLa cells in a synergistic manner with miR-16 and/or miR-34a.

Involvement of the endogenous opioid system in the beneficial influence of physical exercise on amphetamine-induced addiction parameters.

Psychostimulant drugs addiction is a chronic public health problem and individuals remain susceptible to relapses increasing public expenses even after withdrawal and treatment. Our research group has focused on finding new therapies to be employed in drug addiction treatment, suggesting the physical exercise as a promising tool. This way, it is necessary to know the mechanisms involved in the beneficial influences of physical exercise observing the pathway that could be explored in drug addiction treatment. Male Wistar rats were conditioned with amphetamine (AMPH) following the conditioned place preference (CPP) protocol and subsequently submitted to swimming for 5 weeks (1 h per day, 5 days per week). Half of the animals were injected with Naloxone (0.3 mg/mL/kg body weight, i.p.) 5 min prior each physical exercise day. After AMPH-CPP re-exposure, our outcomes showed that physical exercise, in addition to minimizing the relapse behavior in the CPP, it increased D1R, D2R and DAT in the Ventral Tegmental Area (VTA), but not in the Nucleus accumbens (NAc). Interestingly, while naloxone inhibited the partial beneficial influence of the exercise on drug-relapse behavior, exercise-induced changes in the dopaminergic system were not observed in the group administered with naloxone as well. Based on these evidences, besides reinforcing the beneficial influence of the physical exercise on AMPH-induced drug addiction, we propose the involvement of endogenous opioid system activation, not as a single one, but as a possible mechanism of action resulting from the physical activity practice, thus characterizing an important therapeutic approach, which may contribute to drug withdrawal consequently preventing relapse.

Physical exercise modifies behavioral and molecular parameters related to opioid addiction regardless of training time.

Addiction is a devastating worldwide disorder that requires effective and innovative therapies. Physical exercise could be useful in addiction treatment because it shares a common neural circuit with addictive drugs. Based on this, molecular adaptations consequent to time of exercise in opioid exposed animals were evaluated. Rats were designed as sedentary (SED) or exercised (EXE). This last group was separated to perform three different periods of swimming: short-term (S-EXE), medium-term (M-EXE) and long-term (L-EXE) for 14, 28 and 42 days, respectively. On the last exercising week, one-half of the animals from SED and all animals from S-, M- and l-EXE were concomitantly exposed to morphine-conditioned place preference (CPP) paradigm and y-maze task for behavioral assessments followed by molecular assays in both Nucleus accumbens (NAc) and hippocampus. Between SED groups, morphine conditioning showed drug-CPP and increased dopamine transporter (DAT), dopamine receptor type-1 (D1R), type-2 (D2R) and glucocorticoid receptor (GR) in both brain areas in relation to saline group. Besides the small morphine-CPP in relation to SED group, all periods decreased DAT, D1R, and GR immunoreactivity in NAc, DAT and D1R in hippocampus, while D2R in both brain areas and GR in hippocampus were primarily decreased by L-EXE. Our findings show that even a short-term exercise modifies behaviors related to drug withdrawal, changing DA targets and GR, which are closely linked to addiction. Therefore, our outcomes involving physical exercise are interesting to perform a possible clinical trial, thus expanding the knowledge about drug addiction.

Tactile Stimulation on Adulthood Modifies the HPA Axis, Neurotrophic Factors, and GFAP Signaling Reverting Depression-Like Behavior in Female Rats.

Depression is a common psychiatric disease which pharmacological treatment relieves symptoms, but still far from ideal. Tactile stimulation (TS) has shown beneficial influences in neuropsychiatric disorders, but the mechanism of action is not clear. Here, we evaluated the TS influence when applied on adult female rats previously exposed to a reserpine-induced depression-like animal model. Immediately after reserpine model (1 mg/kg/mL, 1×/day, for 3 days), female Wistar rats were submitted to TS (15 min, 3×/day, for 8 days) or not (unhandled). Imipramine (10 mg/kg/mL) was used as positive control. After behavioral assessments, animals were euthanized to collect plasma and prefrontal cortex (PFC). Behavioral observations in the forced swimming test, splash test, and sucrose preference confirmed the reserpine-induced depression-like behavior, which was reversed by TS. Our findings showed that reserpine increased plasma levels of adrenocorticotropic hormone and corticosterone, decreased brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B, and increased proBDNF immunoreactivity in the PFC, which were also reversed by TS. Moreover, TS reestablished glial fibrillary acidic protein and glucocorticoid receptor levels, decreased by reserpine in PFC, while glial cell line-derived neurotrophic factor was increased by TS per se. Our outcomes are showing that TS applied in adulthood exerts a beneficial influence in depression-like behaviors, modulating the HPA axis and regulating neurotrophic factors more effectively than imipramine. Based on this, our proposal is that TS, in the long term, could be considered a new therapeutic strategy for neuropsychiatric disorders improvement in adult life, which may represent an interesting contribution to conventional pharmacological treatment.

Dysphagia Incidence after Outpatient Anterior Cervical Surgery Using Instrumentation versus No Instrumentation / Incidencia de la disfagia tras la cirugía cervical anterior ambulatoria con instrumentación y sin instrumentación

ABSTRACT Objective: Dysphagia is a relatively common occurrence in the postoperative period following anterior cervical surgery, with some indicating rates as high as 79%. In most cases, it remains only a transient phenomenon. The cause has been debated, with most speculating injury to nerves in the swallowing mechanism. The objective of this study was to determine if the presence of instrumentation during anterior cervical surgery in the outpatient setting would affect the incidence, duration and severity of dysphagia. Methods: We did a retrospective review of the medical records of 50 consecutive patients who had undergone single-level instrumented anterior cervical discectomy and fusion. Then we compared that group with our control group of 50 patients who had had simple single-level anterior cervical discectomy without instrumentation or fusion. The patients were evaluated for the presence of dysphagia as well as neck disability index outcome scores. Results: There was no significant difference between the groups in postoperative neck disability index outcomes at the two-year follow-up (p = 0.182). Dysphagia occurred only in the instrumented group, with an incidence of 12% (six patients): their symptoms lasted on average three weeks, and all six patients experienced only mild severity on the Bazaz-Yoo scale. There was statistically significant difference between the two groups (p = 0.012). Conclusion: There was a greater trend towards postoperative dysphagia in cases with instrumentation (12% of the patients). Dysphagia was transient with mild severity in patients who received instrumentation compared with those who underwent discectomy alone.

RESUMEN Objetivo: La disfagia es una ocurrencia relativamente común en el período postoperatorio después de la cirugía cervical anterior, con algunas tasas indicadoras tan altas como 79%. En la mayoría de los casos, sigue siendo sólo un fenómeno transitorio. Su causa ha sido discutida, atribuyéndose principalmente a una lesión en los nervios del mecanismo de deglución. El objetivo de este estudio fue determinar si la presencia de la instrumentación durante la cirugía cervical anterior en el contexto ambulatorio afectaría la incidencia, duración y severidad de la disfagia. Métodos: Realizamos una revisión retrospectiva de las historias clínicas de 50 pacientes consecutivos que habían tenido discectomía y fusión cervical anterior con instrumentación a un solo nivel. Entonces comparamos ese grupo con nuestro grupo de control de 50 pacientes a quienes se les había practicado una discectomía cervical anterior a un solo nivel simple sin instrumentación o fusión. Los pacientes fueron evaluados con respecto a la presencia de disfagia, así como en relación con las puntuaciones del resultado del índice de la discapacidad cervical. Resultados: No hubo diferencias significativas entre los grupos en cuanto a los resultados del índice de discapacidad cervical postoperatorio en el seguimiento de dos años (p = 0.182). La disfagia se produjo sólo en los grupos con instrumentación, con una incidencia de 12% (seis pacientes): sus síntomas duraron un promedio de tres semanas, y los seis pacientes experimentaron toda una severidad leve en la escala de Bazaz-Yoo. Hubo una diferencia estadísticamente significativa entre los dos grupos (p = 0.012). Conclusión: Hubo una mayor tendencia a la disfagia postoperatoria en los casos con instrumentación (12% de los pacientes). La disfagia fue transitoria con severidad leve en los pacientes que recibieron instrumentación, comparada con la de los que experimentaron discectomía solamente.

Influence of physical activity on addiction parameters of rats exposed to amphetamine which were previously supplemented with hydrogenated vegetable fat.

Amphetamine (AMPH) and its derivatives are addictive drugs used to promote and enhance alertness, motivation, willingness, courage and wellbeing. However, their chronic use is related to memory loss, emotional instability, insomnia, psychosis and paranoia. In the last decades, modern society has included processed foods, rich in trans fatty acids (TFA), in their diet, what has been related to several health problems including increased AMPH preference and self-administration. In this scenario, physical activity appears to be useful to attenuate rewarding symptoms related to addictive drugs mainly by affecting brain neuroplasticity and neurotransmission. The current study has been developed to assess the influence of physical activity on addiction parameters of rats exposed to AMPH which were previously supplemented with hydrogenated vegetable fat (HVF), rich in TFA. After six weeks of HVF or soybean oil (SO, control group) supplementation, adult rats were conditioned with d,l-AMPH or vehicle for 14 days. Then, half of each experimental group was submitted to physical activity in treadmill running sessions (60min/day, 5 days/week) for 5 weeks. Animals were re-conditioned with AMPH or vehicle for 3 more days, to observe drug relapse. Locomotor activity and anxiety-like symptoms were observed 24h after the last AMPH reconditioning, and fatty acids composition was quantified in the ventral tegmental area, striatum and prefrontal cortex. All animals showed AMPH preference, but only SO sedentary showed drug relapse. No differences were observed in locomotor activity among groups, while HVF-supplemented group showed decreased exploration per se, and physical activity prevented this. Moreover, AMPH-HVF group showed increased anxiety-like symptoms, which were prevented by physical activity. These results indicate that HVF supplementation modifies AMPH addiction, whereas regular physical activity could be protective against both AMPH and TFA damages.

Duodenal-jejunal bypass normalizes pancreatic islet proliferation rate and function but not hepatic steatosis in hypothalamic obese rats

Modifications in life-style and/or pharmacotherapies contribute to weight loss and ameliorate the metabolic profile of diet-induced obese humans and rodents. Since these strategies fail to treat hypothalamic obesity, we have assessed the possible mechanisms by which duodenal-jejunal bypass (DJB) surgery regulates hepatic lipid metabolism and the morphophysiology of pancreatic islets, in hypothalamic obese (HyO) rats. During the first 5 days of life, male Wistar rats received subcutaneous injections of monosodium glutamate (4 g/kg body weight, HyO group), or saline (CTL). At 90 days of age, HyO rats were randomly subjected to DJB (HyO DJB group) or sham surgery (HyO Sham group). HyO Sham rats were morbidly obese, insulin resistant, hypertriglyceridemic and displayed higher serum concentrations of non-esterified fatty acids (NEFA) and hepatic triglyceride (TG). These effects were associated with higher expressions of the lipogenic genes and fatty acid synthase (FASN) protein content in the liver. Furthermore, hepatic genes involved in β-oxidation and TG export were down-regulated in HyO rats. In addition, these rats exhibited hyperinsulinemia, β-cell hypersecretion, a higher percentage of islets and β-cell area/pancreas section, and enhanced nuclear content of Ki67 protein in islet-cells. At 2 months after DJB surgery, serum concentrations of TG and NEFA, but not hepatic TG accumulation and gene and protein expressions, were normalized in HyO rats. Insulin release and Ki67 positive cells were also normalized in HyO DJB islets. In conclusion, DJB decreased islet-cell proliferation, normalized insulinemia, and ameliorated insulin sensitivity and plasma lipid profile, independently of changes in hepatic metabolism.

Anopheles darlingi polytene chromosomes: revised maps including newly described inversions and evidence for population structure in Manaus.

Salivary gland polytene chromosomes of 4th instar Anopheles darlingi Root were examined from multiple locations in the Brazilian Amazon. Minor modifications were made to existing polytene photomaps. These included changes to the breakpoint positions of several previously described paracentric inversions and descriptions of four new paracentric inversions, two on the right arm of chromosome 3 and two on the left arm of chromosome 3 that were found in multiple locations. A total of 18 inversions on the X (n = 1) chromosome, chromosome 2 (n = 7) and 3 (n = 11) were scored for 83 individuals from Manaus, Macapá and Porto Velho municipalities. The frequency of 2Ra inversion karyotypes in Manaus shows significant deficiency of heterozygotes (p < 0.0009). No significant linkage disequilibrium was found between inversions on chromosome 2 and 3. We hypothesize that at least two sympatric subpopulations exist within the An. darlingi population at Manaus based on inversion frequencies.

Anopheles darlingi polytene chromosomes: revised maps including newly described inversions and evidence for population structure in Manaus

Salivary gland polytene chromosomes of 4th instar Anopheles darlingi Root were examined from multiple locations in the Brazilian Amazon. Minor modifications were made to existing polytene photomaps. These included changes to the breakpoint positions of several previously described paracentric inversions and descriptions of four new paracentric inversions, two on the right arm of chromosome 3 and two on the left arm of chromosome 3 that were found in multiple locations. A total of 18 inversions on the X (n = 1) chromosome, chromosome 2 (n = 7) and 3 (n = 11) were scored for 83 individuals from Manaus, Macapá and Porto Velho municipalities. The frequency of 2Ra inversion karyotypes in Manaus shows significant deficiency of heterozygotes (p < 0.0009). No significant linkage disequilibrium was found between inversions on chromosome 2 and 3. We hypothesize that at least two sympatric subpopulations exist within the An. darlingi population at Manaus based on inversion frequencies.

Why SINBAD? Describing diabetic foot ulcers in a Barbados population

OBJECTIVE: Here, we report on the characterization of diabetic foot ulcers in a Barbados population using the SINBAD ulcer classification system. SUBJECTS AND METHODS: Sixty-five case participants were seen and 73 ulcers presented. All ulcers were categorized upon examination using the SINBAD classification scheme: Site, Ischaemia, Neuropathy, Bacterial infection, Area, Depth. The individual category scores were summed to create a SINBAD score with a range of 0–6.Results were compiled and analysis performed using Stata SE 12.1 (Stata Corporation). RESULTS: Mean age of the participants was 56.75 (± 9.03SD) years and more were men (53.4%). The mean diabetes duration was 15.25 (± 9.84 SD) years. Three SINBAD scores (1, 2 and 3) shared the majority of the ulcers at 26.0% each. The next highest was SINBAD score 0 at 15.1% of the ulcers, followed by the SINBAD score 4at 6.9%. None of the ulcers seen in the participants (0%)registered a SINBAD score of 5 or 6. The majority of the ulcers were neuropathic (61.64% vs 38.36%), larger than 1cm2 (63.01% vs 36.99%), free of bacterial infection(95.89% vs 4.11%) and confined to the skin and subcutaneous tissue (100% vs 0%). CONCLUSION: The SINBAD ulcer classification score indicates the risk of a foot wound failing to heal, with scores of three and above having a significantly increased time to heal and being classified as complicated. In the current study, 67% of the ulcers seen were scored below the threshold of a SINBAD score of 3.

Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis

We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.

Platelet-rich plasma releasate differently stimulates cellular commitment toward the chondrogenic lineage according to concentration.

Platelet-rich plasma has been used to treat articular cartilage defects, with the expectations of anabolic and anti-inflammatory effects. However, its role on cellular chondrogenic or fibrogenic commitment is still a controversy. Herein, the role of platelet-rich plasma releasate, the product obtained following platelet-rich plasma activation, on cellular commitment toward the chondrogenic lineage was evaluated in vitro. Human nasoseptal chondrogenic cells and human bone marrow mesenchymal stromal cells were used as cell types already committed to the chondrogenic lineage and undifferentiated cells, respectively, as different concentrations of platelet-rich plasma releasate were tested in comparison to commonly used fetal bovine serum. Low concentration of platelet-rich plasma releasate (2.5%) presented similar effects on cellular growth compared to 10% fetal bovine serum, for both cell types. In a three-dimensional culture system, platelet-rich plasma releasate alone did not induce full nasoseptal chondrogenic cells cartilage-like pellet formation. Nonetheless, platelet-rich plasma releasate played a significant role on cell commitment as high-passage nasoseptal chondrogenic cells only originated cartilage-like pellets when expanded in the presence of platelet-rich plasma releasate rather than fetal bovine serum. Histological analyses and measurements of pellet area demonstrated that even low concentrations of platelet-rich plasma releasate were enough to prevent nasoseptal chondrogenic cells from losing their chondrogenic potential due to in vitro expansion thereby promoting their recommitment. Low concentration of platelet-rich plasma releasate supplemented in chondrogenic medium also increased the chondrogenic potential of mesenchymal stromal cells seeded on collagen-hyaluronic acid scaffolds, as observed by an increase in chondrogenic-related gene expression, sulfated glycosaminoglycan production, and compressive modulus following in vitro culture. On the contrary, higher concentration of platelet-rich plasma releasate (10%) hampered some of these features. In conclusion, platelet-rich plasma releasate was able to prevent cellular chondrogenic capacity loss, inducing regain of their phenotype, and modulate cell commitment. Our data support the hypothesis of platelet-rich plasma chondrogenic potential, allowing fetal bovine serum substitution for platelet-rich plasma releasate at specific concentrations in culture medium when chondrogenic commitment is desired on specific cell types and moments of culture.

Análises das embalagens de plantas medicinais comercializadas em farmácias e drogarias do município de Ijuí/RS / Analyses of the packages of medicinal plants sold in pharmacies in the city of Ijuí - RS, Brazil

RESUMO: O objetivo deste estudo foi analisar as embalagens de plantas medicinais comercializadas em farmácias e drogarias do município de Ijuí/RS, a partir das legislações vigentes sobre o tema. A coleta de dados foi realizada na primeira quinzena do mês de dezembro de 2011 em 13 estabelecimentos farmacêuticos localizados na região central do município, através de formulário elaborado a partir da legislação. Foram selecionadas para análise, plantas medicinais acondicionadas em diferentes tipos de embalagens e marcas. Foram avaliadas 44 embalagens de plantas medicinais, das quais 71% estavam irregulares no que se refere a indicação terapêutica e ao modo de preparo, considerando o preconizado pela RDC 10/10. Embora nem todas as drogas vegetais analisadas estivessem notificadas nesta Resolução, considerou-se o mesmo critério para todas as amostras analisadas. Além disso, 16% dos produtos analisados não apresentavam segurança quanto ao acondicionamento. A nomenclatura popular estava presente em todas as amostras, enquanto a nomenclatura botânica em apenas 75%. Conclui-se que todas as embalagens analisadas apresentaram alguma irregularidade em relação ao que estabelece a RDC nº10/2010, tendo em vista que nenhuma apresentou todos os requisitos exigidos por ela. Os resultados observados demonstram que a ausência das informações devidas nas embalagens ou nos folhetos informativos para orientar os consumidores, pode comprometer o uso seguro das plantas e prejudicar a saúde dos usuários.

ABSTRACT: This study aimed to analyze the packages of medicinal plants sold in pharmacies and drugstores in the city of Ijuí, state of Rio Grande do Sul, Brazil, according to the Brazilian legislation about the subject. Data collection was conducted in December 2011 in 13 selected pharmaceutical establishments located downtown, and data were collected using a form prepared from the aforementioned resolution. The medicinal plants included in the analysis were from different types of packages and brands. We evaluated 44 packages of medicinal plants, of which 71% were irregular in relation to shape, therapeutic indication and method of preparation. Moreover, 16% of the total products tested had no package security. The popular nomenclature was present in all samples, while the botanical nomenclature, in 75%. We concluded that all analyzed packages were irregular according to the Brazilian RDC 10/2010 because none of them had all of the requirements. The results observed, such as lack of information on the packages or leaflets to guide consumers, may compromise the safe use of plants and endanger the health of users.

Trans-fat supplementation over two generations of rats exacerbates behavioral and biochemical damages in a model of mania: Co-treatment with lithium.

AIMS: We investigated whether trans-fat supplemented over two generations of rats could alter neuronal membranes and influence mania-like behaviors, as well as the effects of lithium (Li). MAIN METHODS: Two generations of female rats were supplemented with soybean oil (SO-C, rich in n-6 fatty acids - FA) or hydrogenated vegetable fat (HVF, rich in trans-fatty acids - TFA). Male rats born from the 1st and 2nd generations were maintained in the same supplementation until adulthood, when they were exposed to an amphetamine (AMPH)-induced model of mania and co-treated with Li or not. KEY FINDINGS: AMPH increased locomotion of both generations and this influence was higher in the HVF than in the SO-C group. Conversely, AMPH increased long-term memory in SO-C group of the 2nd generation. HVF supplementation allowed hippocampal TFA incorporation in rats of both generations (0.1 and 0.2%, respectively). Oxidative parameters indicated higher levels of protein carbonyl (PC) in the HVF group with no changes in catalase (CAT) activity in the 1st generation. In the 2nd generation, AMPH increased PC levels of both experimental groups, whereas CAT activity was lower per se in the HVF group only. The co-treatment with Li leveled out all behavioral parameters, PC levels and CAT activity indicating a significant neuroprotective role. SIGNIFICANCE: These findings suggest that chronic HVF consumption allows a rising incorporation of TFA in the brain, which may be reflected on the neuropsychiatric conditions related to mania, whereas the effects of Li are not modified in the course of this harmful dietary habit.

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc) prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25) or high-dose (1.2 mg/kg, group H, n=25) rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0), after induction (T1), after rocuronium (just before laryngoscopy; T2), 2 min after intubation (T3), and 5 min after intubation (T4). The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001), and 459 vs 434 ms in group H (P=0.005)]. The incidence of dysrhythmias in group C (28%) and in group H (24%) was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation.

Spatio-temporal characteristics of hurdle runs and ergometric tests during athletic preparation / Características espaço-temporais de corridas com obstáculo e testes ergométricos durante a preparação no atletismo

The main goal of this study was to assess the appropriateness of both ergometric and modified hurdles tests for an annual cycle of hurdlers who were working on mastering the 400 m distance. Nine Polish hurdlers (personal best: 54.46±2.16 s, age: 20.67±1.87 years) were chosen as the research participants. In each of two mastering periods in the research, an ergometric test and a specific test were implemented during a hurdle run. In February, an interval ergometric test (5×6 s) and an interval hurdle test (IHT) were performed. Additionally, in May, a classic Wingate test and a 200 m hurdle run were introduced. With regard to the ergometric tests, we assessed the following measurements: maximum power (Pmax) and mean power (P×) reached in five repetitions as well as total work (Wtotal) performed in five attempts. The Mann-Whitney test was used to distinguish between the athletic test results obtained in the preparation period outlined above and those obtained in the first period. Lactate (LA) concentrations were assessed with the Chi-square test. Moreover, Spearman's rank correlation coefficients were used in the analysis. The achieved study results indicate the lack of significant differentiation of the ergometric test parameters (p≥ 0.05). The spatial structure of both specific tests (5×2 H v. 200 m H) was similar given that the first and the second parts of both hurdle races and the number of steps taken were similar. The basic parameters of the ergometric tests did not exhibit any relationship with the recommended record time achieved for the 400 m hurdle run.

O objetivo deste estudo foi avaliar a idoneidade de seleção dos testes ergométricos e testes modificados de corridas com barreiras ao longo do ciclo anual de treinamento dos atletas na distância de 400m. Participaram do estudo nove atletas poloneses (melhor resultado: 54,46±2,16s, idade: 20,67±1.87 anos). Em duas temporadas de treinamento foram realizados dois testes: ergométrico e especial (=na corrida com barreiras). Em fevereiro foi efetuado o teste ergonómico em intervalos (95x6s) e o teste com barreiras Rest com intervalos (IHT). Em maio foi efetuado o teste clássico de 30 s Wingate e uma corrida de 200m com barreiras (200mH). Nas corridas com barreiras foram considerados os parâmetros de tempo, potência máxima (Pmax), potência média (Px) e trabalho total (Wtotal). Para avaliar as diferenças entre os resultados dos testes numa temporada foi aplicado o teste de Mann-Whithney. As diferenças de concentração do lactato (LA) foram avaliadas com o teste Chi-square. Na análise foram considerados também os coeficientes de correlação de postos de Spearman. Os resultados dos estudos demostram a ausência de diferenças pertinentes nos parâmetros dos testes ergométricos (p ≥ 0,05). A estrutura espacial de ambos os testes especiais (5x2H vs. 200mH) foi semelhante: na primeira e segunda parte de ambas as corridas foi efetuado o número parecido dos passos. Os parâmetros essenciais dos testes ergométricos (Pmax, Px, Wtotal) não demostraram relações importantes com o resultado recorde na corrida de 400m com barreiras. A análise demostrou a possibilidade de utilização seletiva dos testes ergométricos na avaliação do grau de preparação dos atletas para a distância de 400m com barreiras.