Effects of unilateral stereotactic posterior striatotomy on harmaline‐induced tremor in rats

Although long known and the most prevalent movement disorder, pathophysiology of essential tremor (ET) remains controversial. The most accepted hypothesis is that it is caused by a dysfunction of the olivocerebellar system. Vilela Filho et al. [2001; Stereotact Funct Neurosurg 77:149–150], however, reported a patient with unilateral hand ET that was completely relieved after a stroke restricted to the contralateral posterior putamen and suggested that ET could be the clinical manifestation of posterior putamen hyperactivity. The present study was designed to evaluate this hypothesis in the most often used model of ET, harmaline‐induced tremor in rats. Fifty‐four male Wistar rats were randomly distributed into three groups: experimental (EG), surgical control (SCG), and pharmacological control (PCG) groups. EG animals underwent stereotactic unilateral posterior striatotomy. SCG rats underwent sham lesion at the same target. PCG served exclusively as controls for harmaline effects. All animals received, postoperatively, intraperitoneal harmaline, and the induced tremor was video‐recorded for later evaluation by a blind observer. Thirteen animals were excluded from the study. Limb tremor was reduced ipsilaterally to the operation in 20 of 21 rats of EG and in two of nine of SCG, being asymmetric in one of 10 of PCG rats. Comparisons between EG × SCG and EG × PCG were statistically significant, but not between SCG × PCG. Limb tremor reduction was greater in anterior than in posterior paws. Lateral lesions yielded better results than medial lesions. These results suggest that the posterior striatum is involved with harmaline‐induced tremor in rats and support the hypothesis presented. © 2013 Wiley Periodicals, Inc.     

Epidemiology of childhood conduct problems in Brazil: systematic review and meta-analysis

Purpose

This study aimed to review evidence on the prevalence of and risk factors for conduct problems in Brazil.

Methods

We searched electronic databases and contacted Brazilian researchers up to 05/2012. Studies were included in the review if they reported the prevalence of or risk factors for conduct problems, conduct disorder, or oppositional defiant disorder for 100 + Brazilian children aged ≤18 years, systematically sampled in schools or the community. Prevalence rates and sex differences were meta-analysed. Risk factor studies were reviewed one by one.

Results

The average prevalence of conduct problems in screening questionnaires was 20.8 %, and the average prevalence of conduct disorder/oppositional defiant disorder was 4.1 %. There was systematic variation in the results of screening studies according to methodology: recruitment location, informants, instruments, impairment criterion for case definition, and response rates. Risk factors previously identified in high-income countries were mainly replicated in Brazil, including comorbid mental health problems, educational failure, low religiosity, harsh physical punishment and abuse, parental mental health problems, single parent family, and low socioeconomic status. However, boys did not always have higher risk for conduct problems than girls.

Conclusions

Studies using screening questionnaires suggest that Brazilian children have higher rates of conduct problems than children in other countries, but diagnostic studies do not show this difference. Risk factors in Brazil were similar to those in high-income countries, apart from child sex. Future research should investigate developmental patterns of antisocial behaviour, employ a variety of research designs to identify causal risk mechanisms, and examine a broader range of risk factors.     

Non-steroidal and steroidal anti-inflammatory use in the context of orthodontic movement

The early phase of orthodontic tooth movement involves sterile acute inflammation of the periodontal ligament in response to biomechanical forces. Anti-inflammatories are pharmacologic agents used in medical and dentistry clinics. The aim of the study was to analyse the bone remodelling during orthodontic movement under non-steroidal and steroidal treatment. Male Wistar rats (n = 90) were randomly divided into three groups: C (control), non-steroidal anti-inflammatory drug (NSAID; potassium diclofenac), and steroidal anti-inflammatory drug (SAID; dexamethasone dissodium phosphate). The animals of the C group received 0.9 per cent saline solution, the NSAID group received potassium diclofenac CATAFLAM? (5 mg/kg), and the SAID group received dexamethasone dissodium phosphate DEXANIL? (2 mg/kg). Animals were sacrificed 3, 7, or 14 days after placement of the orthodontic appliance. The upper first molars were processed histologically; we quantified the blood vessels, Howship lacunae, and osteoclast-like cells present on the tension and compression sides of the periodontal ligament. Bone formation was evaluated under polarized light microscopy; 4.5 Image Pro-Plus? software calculated the percentage of immature/mature collagen present. The results showed that, in 3 and 7 days, NSAID and SAID groups presented fewer blood vessels, Howship lacunae, and osteoclast-like cells when compared to the control group. On the 7th and 14th days, there was a lower percentage of mature collagen in the SAID group (P < 0.001). These data demonstrate that potassium diclofenac and dexamethasone inhibit bone resorption during the initial period of orthodontic movement and that dexamethasone delays the collagen maturation process in established bone matrix.     

The lacuno-canalicular system (LCS) and osteocyte network of alveolar bone by confocal laser scanning microscopy (CLSM)

The osteocyte lacuno-canalicular system (OLCS) is a large network intercommunicating the lacunae and canaliculi which contain the osteocytes and their cytoplasmic processes within the mineralized bone matrix. The vitality and functioning of the osteocytes and cytoplasmic processes depend upon this intercommunication. To date, the 3-dimensional features of OLCS in the alveolar bone have not been studied; therefore the aim of this study was to use confocal scanning microscopy to do so. Samples of alveolar bone from male Wistar rats were fixed in buffer formalin and stained with basic fuchsin to visualize the lacuno-canalicular system. In decalcified samples of the same bone, the actin was labeled using fluorescent phallotoxin to visualize the osteocyte network. The samples were observed at the level of the mesial root of the first upper molar in bucco-palatal direction using a confocal laser scanning microscope. The results showed that in the area near the inner aspect (bundle bone) of the buccal plate, the osteocyte lacunae are oval-shaped and relatively uniform in size, aligned parallel to each other and with their major axes parallel to the periodontal bone surface, and the osteocytes are oval-shaped, with their main axes perpendicular to the periodontal bone surface, and the cytoplasmic processes irradiate in all directions. In the area near the inner aspect (bundle bone) of the palatal plate, the osteocyte lacunae are rounded, have different sizes and their orientation does not follow any specific pattern, and the osteocyte bodies have major axes parallel to the periodontal surface, a larger number of cytoplasmic processes, and run in a straighter direction than in the buccal plate. These results will contribute to the understanding of the changes that may occur in OLCS microarchitecture as a result of a pathological process, surgical technique or force applied to the alveolar bone.     

Inequality in pediatric kidney transplantation in Brazil

Background

The aim of this study was to describe the access and factors associated with kidney transplantation for children in different regions of Brazil.

Methods

We analyzed a cohort of 1211 children enrolled on the transplant list from January 2011 to December of 2013. We fitted regression models to investigate factors associated with: (a) undergoing kidney transplantation from a deceased donor, and (b) being removed from the waiting list.

Results

The incidence of transplantation was uneven across regions, with the lowest rate at 0.4 per million age-related population (pmarp) in the Midwest and the highest incidence rate of 8.3 cases pmarp in the South. Children from the North and the Midwest regions had a 3–4 times lower probability of undergoing a deceased donor transplant (p < 0.05). Apart from the geographic region, age of recipients and GDP influenced the outcome. The likelihood of undergoing transplantation was very low in the youngest children in the North and Midwest. The number of transplant centers was not associated with either outcome.

Conclusions

Factors of inequality in transplantation in Brazil are of macroeconomic origin, but there is room to reduce inequalities. Training existing transplant center professionals in the care of children could diminish the discrepancies.

     

Rosuvastatin treatment prevents progressive kidney inflammation and fibrosis in stroke-prone rats

Salt-loaded, spontaneously hypertensive stroke-prone rats show progressive increases in blood pressure and proteinuria and accumulate acute-phase proteins in body fluids, modeling events during renal damage. The aim of this study was to assess the pathological events occurring in the kidney of spontaneously hypertensive stroke-prone rats over time and evaluate the effects of statin treatment, which is known to improve renal and cardiovascular outcomes. Kidneys of male spontaneously hypertensive stroke-prone rats euthanized at different stages of proteinuria showed progressive inflammatory cell infiltration, the accumulation of alpha-smooth muscle actin-positive cells, degenerative changes in podocytes, and severe fibrosis. These were accompanied by an imbalance in the plasminogen/plasmin and metalloprotease systems characterized by the increased renal expression of plasminogen activator inhibitor-1, tissue plasminogen activator, and urokinase plasminogen activator; the net result was an increase in plasmin and matrix metalloproteinase (MMP)-2 and a reduction in MMP-9 activity. Chronic treatment with the hydrophilic rosuvastatin had renoprotective effects in terms of morphology and inflammation and prevented the changes in plasmin, MMP-2, and MMP-9 activity. These effects were independent of the changes in blood pressure and plasma lipid levels. Treatment with the lipophilic simvastatin was not renoprotective. These data suggest that rosuvastatin may have potential utility as a therapeutic option in renal diseases that are characterized by inflammation and fibrosis.     

Nano-topography: Quicksand for cell cycle progression?

The 3-D spatial and mechanical features of nano-topography can create alternative environments, which influence cellular response. In this paper, murine fibroblast cells were grown on surfaces characterized by protruding nanotubes. Cells cultured on such nano-structured surface exhibit stronger cellular adhesion compared to control groups, but despite the fact that stronger adhesion is generally believed to promote cell cycle progression, the time cells spend in G1 phase is doubled. This apparent contradiction is solved by confocal microscopy analysis, which shows that the nano-topography inhibits actin stress fiber formation. In turn, this impairs RhoA activation, which is required to suppress the inhibition of cell cycle progression imposed by p21/p27. This finding suggests that the generation of stress fibers, required to impose the homeostatic intracellular tension, rather than cell adhesion/spreading is the limiting factor for cell cycle progression. Indeed, nano-topography could represent a unique tool to inhibit proliferation in adherent well-spread cells.