Anatomical and radiographic appearance of the capuchin monkey thoracic cavity (Cebus apella)

The capuchin monkey is widespread both north and south of the Legal Amazon and in the Brazilian cerrado. Ten clinically healthy capuchin monkeys were submitted to an anatomical and radiographic study of their thoracic cavities. The radiographic evaluation allowed the description of biometric values associated with the cardiac silhouette and thoracic structures. Application of the VHS (vertebral heart size) method showed positive correlation (P<0.05) with depth of the thoracic cavity, as well as between the body length of vertebrae T3, T4, T5 and T6 and the cardiac length and width. The lung fields showed a diffuse interstitial pattern, more visible in the caudal lung lobes and a bronchial pattern in the middle and cranial lung lobes. The radiographic examination allowed preliminary inferences to be made concerning the syntopy of the thoracic structures and modification of the pulmonary patterns and cardiac anatomy for the capuchin monkey.

Thoracic and heart biometrics of non-anesthetized agouti (Dasyprocta primnolopha Wagler, 1831) measured on radiographic images

The agouti is a species intensively hunted throughout the Amazon and the semi-arid regions of northeastern Brazil. Considering the current trend in conservation management of wild species, the aim of this study was to determine the morphometric reference to the heart of agouti raised in captivity, based on thoracic and cardiac measurements in these animals. Thirty adult agoutis, 1 to 3 years of age, without clinical signs of cardiac disease were selected. The animals were physically restrained and radiographies in laterolateral (LL) and ventrodorsal (VD) recumbence were produced. The following measures were taken: the apicobasilar length of the heart (at the most cranial height of the Carina region to the heart apex) (AB), maximum width of the heart perpendicular to AB (CD), heart inclination angle (AIC), trachea inclination angle (AIT), distance from the right heart wall (DPTd), distance from the left heart wall (DPTe) and vertical depth of the thorax, and the ventral face of the vertebral column to the dorsal border of the sternum at the level of the trachea bifurcation (H). The ratios between AB/CD, AB/H and CD/H were also analyzed. To calculate the vertebral heart scale (VHS), the AB and CD measurements were laid over the thoracic vertebra starting at T4. Radiographic evaluation showed values consistent with those reported in small animals and some wild and exotic species. The main biometric values in the chest cavity and heart of agouti are arranged as follows: (1) The ratios between AB/H ratio and CD/H were not sensitive for identifying heart increases (p>0.05), while the ratio AB/CD was more sensitive in this identification (p<0.05); (2) AIC: 21.2±6.4º (mean between male and famale); (3) AIT for males and females: 9.93±3.23° and 8.4±3.94°; (4) DPTd and DPTe for males: 0.97±0.40cm and 0.7±0.30cm; (5) DPTd and DPTe for females: 1.12±0.42cm and 01.02±0.43cm; (6) VHS for males and females: 7.75±0.48v e 7.61±0.34v; (7) The caudal vena cava (CVC) was visualized dorsal-cranially and located right of the midline. The data obtained allowed the acquisition of the first reference values for biometry of the heart of agoutis, contributing to better understanding of cardiac morphology and identification of cardiomyopathy in these animals.

The role of B-mode ultrasonography in the musculoskeletal anatomical evaluation of the cervical region of the dog spine

This study characterized the normal musculoskeletal anatomy of the cervical segment of the spine of dogs by means of B-mode ultrasonography. The objective was to establish the role of B-mode ultrasonography for the anatomical evaluation of the cervical spine segment in dogs, by comparing the ultrasonographic findings with images by computed tomography and magnetic resonance imaging. The ultrasound examination, in transverse and median sagittal sections, allowed to identify a part of the epaxial cervical musculature, the bone surface of the cervical vertebrae and parts of the spinal cord through restricted areas with natural acoustic windows, such as between the atlanto-occipital joint, axis and atlas, and axis and the third cervical vertebra. The images, on transverse and sagittal planes, by low-field magnetic resonance imaging, were superior for the anatomical identification of the structures, due to higher contrast between the different tissues in this modality. Computed tomography showed superiority for bone detailing when compared with ultrasonography. As for magnetic resonance imaging, in addition to the muscles and cervical vertebrae, it is possible to identify the cerebrospinal fluid and differentiate between the nucleus pulposus and annulus fibrosus of the intervertebral discs. Although not the scope of this study, with knowledge of the ultrasonographic anatomy of this region, it is believed that some lesions can be identified, yet in a limited manner, when compared with the information obtained mainly with magnetic resonance imaging. The ultrasound examination presented lower morphology diagnostic value compared with the other modalities.

Anaesthesia and Pain Management for Use in Orthopaedic Day Surgery

Day surgery has gained a large popularity during the last decades. In Finland, 57% of the elective procedures, and 50% at Turku University Hospital, were already conducted on day basis during 2012. The steady growth of day surgery is mostly due to an increased safety in perioperative care and cost-effectiveness. The development of surgical techniques and anaesthetic methods has advanced the modern day surgery and extended the repertory of the procedures for use in day surgery operations. Day surgery also offers certain benefits like reduced risk for hospital-related infections, stress and confusion. Patient satisfaction, regarding several issues, is high. Most concerns and complaints are related to postoperative pain, nausea and vomiting pain and nausea. Pain can hamper recovery and pain management is a crucial factor for hospital discharge. Appropriate pain treatment is effective, safe, easy and economical. A procedure-specific approach and an individually planned, multimodal analgesia should be the basis of modern pain management. The main aim of this thesis was to evaluate the effectiveness and safety of anaesthetic technique and methods in pain treatment of orthopaedic day case surgery, and following conclusions were made. Unilateral spinal block was achieved using hyperbaric bupivacaine with a small dose of clonidine but clonidine prolonged the block. Continuous subacromial bupivacaine was found to be safe but conferring only moderate efficacy in pain care after shoulder arthroscopy. Transdermal fentanyl, 12 g/h, as part of multimodal analgesia, offered a safe and easy option to pain management in this patient group. However, after forefoot surgery, it did not reduce pain any further. In general, pain scores in all patient groups were low and the need for rescue opioid moderate.

Antinociceptive effect of intrathecal neostigmine evaluated in rats by two different pain models

The analgesic efficacy of cholinergic agonists and anticholinesterase agents has been widely recognized. The analgesic effect obtained by activating cholinergic mechanisms, however, seems to depend on the experimental pain model utilized for its evaluation. The antinociceptive effect of intraspinal neostigmine was examined in rats submitted concurrently to the tail flick and formalin tests. Neostigmine (8.25 and 16.5 nmol) produced a dose-dependent antinociceptive effect in the tail flick test (a model of phasic pain) and reduced the first phase (phasic pain) of the animal response to formalin also in a dose-dependent manner. The second phase (tonic pain) of the response to formalin, however, was slightly reduced after a longer period of time only by the higher dose of the anticholinesterase. The effect of neostigmine was not significantly different when the drug was injected into rats submitted exclusively to the tail flick test. The second phase of the animal response to formalin was slightly reduced by neostigmine (8.25 nmol) and strongly inhibited by the higher dose of the anticholinesterase when injection was made after the first phase. We conclude that phasic and tonic pain can both be controlled by high doses of neostigmine. In addition, we show that inhibition by a lower dose of neostigmine of the formalin-induced phasic pain did not prevent the subsequent occurrence of tonic pain produced by the irritant

Reduced bone mineral density in men after heart transplantation

Heart transplantation is associated with rapid bone loss and an increased prevalence and incidence of fractures. The aim of the present study was to compare the bone mineral density (BMD) of 30 heart transplant (HT) recipients to that of 31 chronic heart failure (CHF) patients waiting for transplantation and to determine their biochemical markers of bone resorption and hormone levels. The BMD of lumbar spine and proximal femur was determined by dual-energy X-ray absorptiometry. Anteroposterior and lateral radiographs of the thoracic and lumbar spine were also obtained. The mean age of the two groups did not differ significantly. Mean time of transplantation was 25.4 ± 21.1 months (6 to 88 months). Except for the albumin levels, which were significantly higher, and magnesium levels, which were significantly lower in HT patients when compared to CHF patients, all other biochemical parameters and hormone levels were within the normal range and similar in the two groups. Both groups had lower BMD of the spine and proximal femur compared to young healthy adults. However, the mean BMD of HT patients was significantly lower than in CHF patients at all sites studied. Bone mass did not correlate with time after transplantation or cumulative dose of cyclosporine A. There was a negative correlation between BMD and the cumulative dose of prednisone. These data suggest that bone loss occurs in HT patients mainly due to the use of corticosteroids and that in 30% of the patients it can be present before transplantation. It seems that cyclosporine A may also play a role in this loss.

Anti-hyperalgesic effect of electroacupuncture in a model of post-incisional pain in rats

Electroacupuncture has been proposed to be a low cost and practical method that allows effective pain management with minimal collateral effects. In this study we have examined the effect of electroacupuncture against the hyperalgesia developed in a model of post-incisional pain in rats. A 1-cm longitudinal incision was made through the skin and fascia of the plantar region of the animal hind paw. Mechanical hyperalgesia in the incision was evaluated 135 min after the surgery with von Frey filaments. The tension threshold was reduced from 75 g (upper limit of the test) to 1.36 ± 0.36 g (mean ± SEM) in control rats. It is shown that a 15-min period of electroacupuncture applied 120 min after surgery to the Zusanli (ST36) and Sanyinjiao (SP6) points, but not to non-acupoints, produces a significant and long-lasting reduction of the mechanical hyperalgesia induced by the surgical incision of the plantar surface of the ipsilateral hind paw. The tension threshold was reduced from 75 to 27.6 ± 4.2 g in animals soon after the end of electroacupuncture. The mechanical threshold in this group was about 64% less than in control. Electroacupuncture was ineffective in rats treated 10 min earlier with naloxone (1 mg/kg, ip), thus confirming the involvement of opioid mechanisms in the antinociceptive effects of such procedure. The results indicate that post-incisional pain is a useful model for studying the anti-hyperalgesic properties of electroacupuncture in laboratory animals.

Translation, adaptation and validation of the Roland-Morris questionnaire - Brazil Roland-Morris

The purpose of the present study was to translate the Roland-Morris (RM) questionnaire into Brazilian-Portuguese and adapt and validate it. First 3 English teachers independently translated the original questionnaire into Brazilian-Portuguese and a consensus version was generated. Later, 3 other translators, blind to the original questionnaire, performed a back translation. This version was then compared with the original English questionnaire. Discrepancies were discussed and solved by a panel of 3 rheumatologists and the final Brazilian version was established (Brazil-RM). This version was then pretested on 30 chronic low back pain patients consecutively selected from the spine disorders outpatient clinic. In addition to the traditional clinical outcome measures, the Brazil-RM, a 6-point pain scale (from no pain to unbearable pain), and its numerical pain rating scale (PS) (0 to 5) and a visual analog scale (VAS) (0 to 10) were administered twice by one interviewer (1 week apart) and once by one independent interviewer. Spearman's correlation coefficient (SCC) and intraclass correlation coefficient (ICC) were computed to assess test-retest and interobserver reliability. Cross-sectional construct validity was evaluated using the SCC. In the pretesting session, all questions were well understood by the patients. The mean time of questionnaire administration was 4 min and 53 s. The SCC and ICC were 0.88 (P<0.01) and 0.94, respectively, for the test-retest reliability and 0.86 (P<0.01) and 0.95, respectively, for interobserver reliability. The correlation coefficient was 0.80 (P<0.01) between the PS and Brazil-RM score and 0.79 (P<0.01) between the VAS and Brazil-RM score. We conclude that the Brazil-RM was successfully translated and adapted for application to Brazilian patients, with satisfactory reliability and cross-sectional construct validity.

Bone mineral density of the lumbar spine of Brazilian children and adolescents aged 6 to 14 years

The authors performed a study of bone mass in eutrophic Brazilian children and adolescents using dual-energy X-ray absorptiometry (DXA) in order to obtain curves for bone mineral content (BMC) and bone mineral density (BMD) by chronological age and correlate these values with weight and height. Healthy Caucasian children and adolescents, 120 boys and 135 girls, 6 to 14 years of age, residents of São Paulo, Brazil, were selected from the Pediatric Department outpatient clinic of Hospital São Paulo (Universidade Federal de São Paulo). BMC, BMD and the area of the vertebral body of the L2-L4 segment were obtained by DXA. BMC and BMD for the lumbar spine (L2-L4) presented a progressive increase between 6 and 14 years of age in both sexes, with a distribution that fitted an exponential curve. We identified an increase of mineral content in female patients older than 11 years which was maintained until 13 years of age, when a new decrease in the velocity of bone mineralization occurred. Male patients presented a period of accelerated bone mass gain after 11 years of age that was maintained until 14 years of age. At 14 years of age the mean BMD values for boys and girls were 0.984 and 1.017 g/cm², respectively. A stepwise multiple regression analysis of paired variables showed that the "vertebral area-age" pair was the most significant in the determination of BMD values and the introduction of a third variable (weight or height) did not significantly increase the correlation coefficient.

Involvement of calcium in pain and antinociception

Calcium ions are widely recognized to play a fundamental role in the regulation of several biological processes. Transient changes in cytoplasmic calcium ion concentration represent a key step for neurotransmitter release and the modulation of cell membrane excitability. Evidence has accumulated for the involvement of calcium ions also in nociception and antinociception, including the analgesic effects produced by opioids. The combination of opioids with drugs able to interfere with calcium ion functions in neurons has been pointed out as a useful alternative for safer clinical pain management. Alternatively, drugs that reduce the flux of calcium ions into neurons have been indicated as analgesic alternatives to opioids. This article reviews the manners by which calcium ions penetrate cell membranes and the changes in these mechanisms caused by opioids and calcium antagonists regarding nociceptive and antinociceptive events.

Antinociceptive potency of aminoglycoside antibiotics and magnesium chloride: a comparative study on models of phasic and incisional pain in rats

A close relationship exists between calcium concentration in the central nervous system and nociceptive processing. Aminoglycoside antibiotics and magnesium interact with N- and P/Q-type voltage-operated calcium channels. In the present study we compare the antinociceptive potency of intrathecal administration of aminoglycoside antibiotics and magnesium chloride in the tail-flick test and on incisional pain in rats, taken as models of phasic and persistent post-surgical pain, respectively. The order of potency in the tail-flick test was gentamicin (ED50 = 3.34 µg; confidence limits 2.65 and 4.2) > streptomycin (5.68 µg; 3.76 and 8.57) = neomycin (9.22 µg; 6.98 and 12.17) > magnesium (19.49 µg; 11.46 and 33.13). The order of potency to reduce incisional pain was gentamicin (ED50 = 2.06 µg; confidence limits 1.46 and 2.9) > streptomycin (47.86 µg; 26.3 and 87.1) = neomycin (83.17 µg; 51.6 and 133.9). The dose-response curves for each test did not deviate significantly from parallelism. We conclude that neomycin and streptomycin are more potent against phasic pain than against persistent pain, whereas gentamicin is equipotent against both types of pain. Magnesium was less potent than the antibiotics and effective in the tail-flick test only.

The distribution of presumptive thoracic paraganglionic tissue in the common marmoset (Callithrix jacchus)

The aortic-pulmonary regions (APR) of seven adult marmosets (Callithrix jacchus) and the region of the right subclavian artery of a further three marmosets were diffusion-fixed with 10% buffered formol-saline solution. In both regions serial 5-µm sections were cut and stained by the Martius yellow, brilliant crystal scarlet and soluble blue method. Presumptive thoracic paraganglionic (PTP) tissue was only observed in the APR. PTP tissue was composed of small groups of cells that varied in size and number. The distribution of the groups of cells was extremely variable, so much so that it would be misleading to attempt to classify their position; they were not circumscribed by a connective tissue capsule, but were always related to the thoracic branches of the left vagus nerve. The cells lay in loose areolar tissue characteristic of this part of the mediastinum and received their blood supply from small adjacent connective tissue arterioles. Unlike the paraganglionic tissue found in the carotid body the cells in the thorax did not appear to have a profuse capillary blood supply. There was, however, a close cellular-neural relationship. The cells, 10-15 µm in diameter, were oval or rounded in appearance and possessed a central nucleus and clear cytoplasm. No evidence was found that these cells possessed a 'companion' cell reminiscent of the arrangement of type 1 and type 2 cells in the carotid body. In conclusion, we found evidence of presumed paraganglionic tissue in the APR of the marmoset which, however, did not show the characteristic histological features of the aortic body chemoreceptors that have been described in some non-primate mammals. A survey of the mediastina of other non-human primates is required to establish whether this finding is atypical for these animals.

JNK regulates dendrite and spine architecture in the central nervous system influencing spatial learning and motor tasks

JNK1 is a MAP-kinase that has proven a significant player in the central nervous system. It regulates brain development and the maintenance of dendrites and axons. Several novel phosphorylation targets of JNK1 were identified in a screen performed in the Coffey lab. These proteins were mainly involved in the regulation of neuronal cytoskeleton, influencing the dynamics and stability of microtubules and actin. These structural proteins form the dynamic backbone for the elaborate architecture of the dendritic tree of a neuron. The initiation and branching of the dendrites requires a dynamic interplay between the cytoskeletal building blocks. Both microtubules and actin are decorated by associated proteins which regulate their dynamics. The dendrite-specific, high molecular weight microtubule associated protein 2 (MAP2) is an abundant protein in the brain, the binding of which stabilizes microtubules and influences their bundling. Its expression in non-neuronal cells induces the formation of neurite-like processes from the cell body, and its function is highly regulated by phosphorylation. JNK1 was shown to phosphorylate the proline-rich domain of MAP2 in vivo in a previous study performed in the group. Here we verify three threonine residues (T1619, T1622 and T1625) as JNK1 targets, the phosphorylation of which increases the binding of MAP2 to microtubules. This binding stabilizes the microtubules and increases process formation in non-neuronal cells. Phosphorylation-site mutants were engineered in the lab. The non-phosphorylatable mutant of MAP2 (MAP2- T1619A, T1622A, T1625A) in these residues fails to bind microtubules, while the pseudo-phosphorylated form, MAP2- T1619D, T1622D, Thr1625D, efficiently binds and induces process formation even without the presence of active JNK1. Ectopic expression of the MAP2- T1619D, T1622D, Thr1625D in vivo in mouse brain led to a striking increase in the branching of cortical layer 2/3 (L2/3) pyramidal neurons, compared to MAP2-WT. The dendritic complexity defines the receptive field of a neuron and dictates the output to the postsynaptic cells. Previous studies in the group indicated altered dendrite architecture of the pyramidal neurons in the Jnk1-/- mouse motor cortex. Here, we used Lucifer Yellow loading and Sholl analysis of neurons in order to study the dendritic branching in more detail. We report a striking, opposing effect in the absence of Jnk1 in the cortical layers 2/3 and 5 of the primary motor cortex. The basal dendrites of pyramidal neurons close to the pial surface at L2/3 show a reduced complexity. In contrast, the L5 neurons, which receive massive input from the L2/3 neurons, show greatly increased branching. Another novel substrate identified for JNK1 was MARCKSL1, a protein that regulates actin dynamics. It is highly expressed in neurons, but also in various cancer tissues. Three phosphorylation target residues for JNK1 were identified, and it was demonstrated that their phosphorylation reduces actin turnover and retards migration of these cells. Actin is the main cytoskeletal component in dendritic spines, the site of most excitatory synapses in pyramidal neurons. The density and gross morphology of the Lucifer Yellow filled dendrites were characterized and we show reduced density and altered morphology of spines in the motor cortex and in the hippocampal area CA3. The dynamic dendritic spines are widely considered to function as the cellular correlate during learning. We used a Morris water maze to test spatial memory. Here, the wild-type mice outperformed the knock-out mice during the acquisition phase of the experiment indicating impaired special memory. The L5 pyramidal neurons of the motor cortex project to the spinal cord and regulate the movement of distinct muscle groups. Thus the altered dendrite morphology in the motor cortex was expected to have an effect on the input-output balance in the signaling from the cortex to the lower motor circuits. A battery of behavioral tests were conducted for the wild-type and Jnk1-/- mice, and the knock-outs performed poorly compared to wild-type mice in tests assessing balance and fine motor movements. This study expands our knowledge of JNK1 as an important regulator of the dendritic fields of neurons and their manifestations in behavior.

An acid-sensing ion channel that detects ischemic pain

Ischemic pain occurs when there is insufficient blood flow for the metabolic needs of an organ. The pain of a heart attack is the prototypical example. Multiple compounds released from ischemic muscle likely contribute to this pain by acting on sensory neurons that innervate muscle. One such compound is lactic acid. Here, we show that ASIC3 (acid-sensing ion channel #3) has the appropriate expression pattern and physical properties to be the detector of this lactic acid. In rats, it is expressed only in sensory neurons and then only on a minority (~40%) of these. Nevertheless, it is expressed at extremely high levels on virtually all dorsal root ganglion sensory neurons that innervate the heart. It is extraordinarily sensitive to protons (Hill slope 4, half-activating pH 6.7), allowing it to readily respond to the small changes in extracellular pH (from 7.4 to 7.0) that occur during muscle ischemia. Moreover, both extracellular lactate and extracellular ATP increase the sensitivity of ASIC3 to protons. This final property makes ASIC3 a "coincidence detector" of three molecules that appear during ischemia, thereby allowing it to better detect acidosis caused by ischemia than other forms of systemic acidosis such as hypercapnia.

Comparison of pre- versus post-incision administration of intraplantar indomethacin and MK886 in a rat model of postoperative pain

The amplification of pain long after the initial stimulus may be avoided if the treatment of pain is introduced before its initiation. However, conflicting evidence exists about the efficacy of such preemptive analgesia for the management of postoperative pain. This study compares the efficacy of intraplantar administration of indomethacin (a non-selective inhibitor of cyclooxygenase) and MK886 (an inhibitor of 5-lipoxygenase-activating protein), separately or in combination to produce preemptive analgesia in a model of surgical incisional pain in male Wistar rats. All incised rats (5 to 6 rats per group) had allodynia at 2, 6, and 24 h after surgery as evaluated using von Frey filaments. MK886, but not indomethacin (50 to 200 µg/paw), reduced the allodynia when injected either 1 h before or 1 h after surgery. The effect of preoperative MK886 (160 µg/paw) against incisional allodynia had a magnitude apparently similar to that produced by postoperative MK886. Pre-, but not postoperative MK886 (80 µg/paw) reduced the allodynia but the effect was seen only at 6 h after surgery. In contrast, MK886 (40 µg/paw) intensified the allodynia observed 2 h after the incision either injected before or after surgery. MK886 or indomethacin alone did not provide preemptive analgesia in the model of incisional pain. In contrast, the combination of MK886 with indomethacin reduced the allodynia more effectively when used before than after surgery, thus fulfilling the criteria for preemptive analgesia. In conclusion, preoperative inhibition of the local generation of both prostaglandins and leukotrienes by surgical incision may be an alternative to provide preemptive analgesia.