Right Orbitofrontal Corticolimbic and Left Corticocortical White Matter Connectivity Differentiate Bipolar and Unipolar Depression

Objectives: The absence of pathophysiologically relevant diagnostic markers of bipolar disorder (BD) leads to its frequent misdiagnosis as unipolar depression (UD). We aimed to determine whether whole brain white matter connectivity differentiated BD from UD depression. Methods: We employed a three-way analysis of covariance, covarying for age, to examine whole brain fractional anisotropy (FA), and corresponding longitudinal and radial diffusivity, in currently depressed adults: 15 with BD-type I (mean age 36.3 years, SD 12.0 years), 16 with recurrent UD (mean age 32.3 years, SD 10.0 years), and 24 healthy control adults (HC) (mean age 29.5 years, SD 9.43 years). Depressed groups did not differ in depression severity, age of illness onset, and illness duration. Results: There was a main effect of group in left superior and inferior longitudinal fasciculi (SLF and ILF) (all F >= 9.8; p <= .05, corrected). Whole brain post hoc analyses (all t >= 4.2; p <= .05, corrected) revealed decreased FA in left SLF in BD, versus UD adults in inferior temporal cortex and, versus HC, in primary sensory cortex (associated with increased radial and decreased longitudinal diffusivity, respectively); and decreased FA in left ILF in UD adults versus HC. A main effect of group in right uncinate fasciculus (in orbitofrontal cortex) just failed to meet significance in all participants but was present in women. Post hoc analyses revealed decreased right uncinate fasciculus FA in all and in women, BD versus HC. Conclusions: White matter FA in left occipitotemporal and primary sensory regions supporting visuospatial and sensory processing differentiates BD from UD depression. Abnormally reduced FA in right fronto-temporal regions supporting mood regulation, might underlie. predisposition to depression in BD. These measures might help differentiate pathophysiologic processes of BD versus UD depression.

Neoplastic Ascites in Osteosarcoma A Case Report

Background Osteosarcoma is a malignant tumor of connective tissue Whose tumor cells produce bone tissue. It can be classified as osteoblastic, chondroblastic, or fibroblastic, according to the predominant histologic type of cells. Its dissemination is hematogenous; and the lungs are the most frequent site of clinically evident metastasis. Extrapulmonary metastases are rare and more frequently diagnosed at necropsy. We present a case of osteosarcoma with peritoneal dissemination that developed neoplastic ascites. Case A 46-year-old patient came to the hospital with a 4-month history of lumbar pain and weakness in the lower limbs. Computed tomography showed blastic lesions in the L3 vertebral body. Surgical resection and histologic analysis revealed a mixed osteoblastic and chondroblastic osteosarcoma. After only one session of chemotherapy, the patient presented a marked clinical worsening with extensive metastatic dissemination and occurrence of voluminous ascites. The cytologic examination of the ascitic fluid demonstrated frequent poorly differentiated tumor cells. The patient died a little more than 2 months after the diagnosis. Conclusion This case is the only report of osteosarcoma primarily focused on the vertebral column affected by peritoneal metastasis shown by cytologic examination of ascitic fluid. (Acta Cytol 2010;54:845-848)

Biomechanical evaluation on tendon reinsertion by comparing trans-osseous suture and suture anchor at different stages of healing: Experimental study on rabbits

Background: Through an experimental biomechanical study on rabbits, tendon reinsertion by means of trans-osseous suture on a spongy bone bed and suture anchor were evaluated comparatively at different phases of healing. Methods: Twenty-four New Zealand White rabbits were used: 2 as pilots, 4 as the control group, and 18 as the experimental group. These 18 animals underwent sectioning and reinsertion of the Achilles tendon bilaterally, using the technique of trans-osseous suture on 1 side and suture anchor on the other. All the pelvic limbs that underwent the procedure were then immobilized for 3 weeks. The experimental group was divided into 3 groups that were sacrificed, respectively, 3, 6, and 12 weeks later. The tendon-bone complex was subjected to biomechanical tests to evaluate the parameters of maximum strength, stiffness, and yield strength. Results: There was no statistically significant difference between the suture anchor group and the trans-osseous suture group, in relation to yield strength (3 weeks, P = .222; 6 weeks, P = .465; and 12 weeks, P = .200) or maximum strength (3 weeks, P = .222; 6 weeks, P = .076; and 12 weeks, P = .078). In relation to stiffness, the suture anchor group showed a statistically significant difference only at 3 weeks of healing ( P = .032) over the trans-osseous suture group. Conclusion: The technique of suturing with an anchor was shown to be similar to the technique of trans-osseous suture for the studied parameters. Level of evidence: Basic Science Study, In-Vitro Biomechanics Study. (C) 2010 Journal of Shoulder and Elbow Surgery Board of Trustees.

Endoscopic-guided percutaneous radiofrequency cordotomy

The authors present the first clinical implementation of an endoscopic-assisted percutaneous anterolateral radiofrequency cordotomy. The aim of this article is to demonstrate the intradural endoscopic visualization of the cervical spinal cord via a percutaneous approach to refine the spinal target for anterolateral cordotomy, avoiding undesired trauma to the spinal tissue or injury to blood vessels. Initially, a lateral puncture of the spinal canal in the C1-2 interspace is performed, guided by fluoroscopy. As soon as CSF is reached by the guide cannula (17-gauge needle), the endoscope can be inserted for visualization of the spinal cord and its surrounding structures. The endoscopic visualization provided clear identification of the pial surface of the spinal cord, arachnoid membrane, dentate ligament, dorsal and ventral root entry zone, and blood vessels. The target for electrode insertion into the spinal cord was determined to be the midpoint from the dentate ligament and the ventral root entry zone. The endoscopic guidance shortened the fluoroscopy usage time and no intrathecal contrast administration was needed. Cordotomy was performed by a standard radiofrequency method after refining of the neurophysiological target. Satisfactory analgesia was provided by the procedure with no additional complications or CSF leak. The initial use of this technique suggests that a percutaneous endoscopic procedure may be useful for particular manipulation of the spinal cord, possibly adding a degree of safety to the procedure and improving its effectiveness. (DOI: 10.3171/2010.4.JNS091779)

Cardiopulmonary Effects of Matching Positive End-Expiratory Pressure to Abdominal Pressure in Concomitant Abdominal Hypertension and Acute Lung Injury

Background: To evaluate the cardiopulmonary effects of positive end-expiratory pressure (PEEP) equalization to intra-abdominal pressure (IAP) in an experimental model of intra-abdominal hypertension (IAH) and acute lung injury (ALI). Methods: Eight anesthetized pigs were submitted to IAH of 20 mm Hg with a carbon dioxide insufflator for 30 minutes and then submitted to lung lavage with saline and Tween (2.5%). Pressure x volume curves of the respiratory system were performed by a low flow method during IAH and ALI, and PEEP was subsequently adjusted to 27 cm center dot H(2)O for 30 minutes. Results: IAH decreases pulmonary and respiratory system static compliances and increases airway resistance, alveolar-arterial oxygen gradient, and respiratory dead space. The presence of concomitant ALI exacerbates these findings. PEEP identical to AP moderately improved oxygenation and respiratory mechanics; however, an important decline in stroke index and right ventricle ejection fraction was observed. Conclusions: Simultaneous IAH and ALI produce important impairments in the respiratory physiology. PEEP equalization to AP may improve the respiratory performance, nevertheless with a secondary hemodynamic derangement.

Role of p21 and oxidative stress on renal tubular resistance after acute ischaemic injury

Background. Subsequent ischaemic episodes may induce renal resistance. P21 is a cell cycle inhibitor that may be induced by oxygen-free radicals and may have a protective effect in ischaemic acute kidney injury (AKI). This study aimed at evaluating the role of oxidative stress and p21 on tubular resistance in a model of acquired resistance after renal ischaemia and in isolated renal tubules. Methods. Wistar rats were divided into: Group 1-sham; Group 2-sham operated and after 2 days submitted to 45-min ischaemia; and Group 3-45-min ischaemia followed after 2 days by a second 45-min ischaemia. Plasma urea was evaluated on Days 0, 2 and 4. Serum creatinine, creatinine clearance and oxidants (thiobarbituric acid-reactive substances) were determined 48 h after the second procedure (Day 4). Histology, immunohistochemistry for lymphocytes (CD3), macrophages (ED1), proliferation (PCNA) and apoptosis (TUNEL) were also evaluated. Rat proximal tubules (PTs) were isolated by collagenase digestion and Percoll gradient from control rats and rats previously subjected to 35 min of ischaemia. PTs were submitted to 15-min hypoxia followed by 45-min reoxygenation. Cell injury was assessed by lactate dehydrogenase release and hydroperoxide production (xylenol orange). Results. Ischaemia induced AKI in Group 2 and 3 rats. Subsequent ischaemia did not aggravate renal injury, demonstrating renal resistance (Group 3). Renal function recovery was similar in Group 2 and 3. Plasma and urine oxidants were similar among in Group 2 and 3. Histology disclosed acute tubular necrosis in Group 2 and 3. Lymphocyte infiltrates were similar among all groups whereas macrophages infiltrate was greater in Group 3. Cell proliferation was greater in Group 2 compared with Group 3. Apoptosis was similar in groups 2 and 3. The p21 expression was increased only in Group 3 whereas it was similar in groups 1 and 2. PTs from the ischaemia group were sensitive to hypoxia but resistant to reoxygenation injury which was followed by lower hydroperoxide production compared to control PT. Conclusion. Renal resistance induced by ischaemia was associated with cell mechanism mediators involving oxidative stress and increased p21 expression.

Elevated Amygdala Activity to Sad Facial Expressions: A State Marker of Bipolar but Not Unipolar Depression

Background: Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BID depressed individuals being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BID and MDD depression. Methods: Sixty adults were recruited: 15 depressed with BID type 1 (BDd), 15 depressed with recurrent MDD, 15 with BID in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series. Results: The BDd-relative to HC, BDr, and MDD-showed elevated left amygdala activity to mild and neutral facial expressions in the sad (p < .009) but not other emotion experiments that was not associated with medication. There were no other significant between-group differences in amygdala activity. Conclusions: Abnormally elevated left amygdala activity to mild sad and neutral faces might be a depression-specific marker in BID but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression.

Abnormal Left and Right Amygdala-Orbitofrontal Cortical Functional Connectivity to Emotional Faces: State Versus Trait Vulnerability Markers of Depression in Bipolar Disorder

Background: Amygdala-orbitofrontal cortical (OFC) functional connectivity (FC) to emotional stimuli and relationships with white matter remain little examined in bipolar disorder individuals (BD). Methods: Thirty-one BD (type 1; n = 17 remitted; n = 14 depressed) and 24 age- and gender-ratio-matched healthy individuals (HC) viewed neutral, mild, and intense happy or sad emotional faces in two experiments. The FC was computed as linear and nonlinear dependence measures between amygdala and OFC time series. Effects of group, laterality, and emotion intensity upon amygdala-OFC FC and amygdala-OFC FC white matter fractional anisotropy (FA) relationships were examined. Results: The BD versus HC showed significantly greater right amygdala-OFC FC (p <= .001) in the sad experiment and significantly reduced bilateral amygdala-OFC FC (p = .007) in the happy experiment. Depressed but not remitted female BD versus female HC showed significantly greater left amygdala-OFC FC (p = .001) to all faces in the sad experiment and reduced bilateral amygdala-OFC FC to intense happy faces (p = .01). There was a significant nonlinear relationship (p = .001) between left amygdala-OFC FC to sad faces and FA in HC. In BD, antidepressants were associated with significantly reduced left amygdala-OFC FC to mild sad faces (p = .001). Conclusions: In BD, abnormally elevated right amygdala-OFC FC to sad stimuli might represent a trait vulnerability for depression, whereas abnormally elevated left amygdala-OFC FC to sad stimuli and abnormally reduced amygdala-OFC FC to intense happy stimuli might represent a depression state marker. Abnormal FC measures might normalize with antidepressant medications in BD. Nonlinear amygdala-OFC FC-FA relationships in BID and HC require further study.

Apolipoprotein E genotype and Cognition in Bipolar Disorder

Apolipoprotein E (APOE) has been extensively studied as a risk factor for sporadic and late onset Alzheimer`s Disease (AD). APOE allele *3, the most frequent variant, is not associated to cognitive dysfunction (CD) or to increased AD risk. Differently, the *4 allele is a well-established risk factor for CD, while the *2 allele is associated with survival and longevity. CD is an important feature of Bipolar Disorder (BD) and recent data suggest that CD may be one of its endophenotypes, although controversial results exist. The aim of this research is to study the association of APOE genotype (APOE) and neurocognitive function in a sample of drug free young BD-type I patients. Sample consisted of 25 symptomatic BD (type I) patients (age 18-35 years old). They were submitted to an extensive neuropsychological evaluation and genotyped for APOE. Subjects with allele *2 presented better cognitive performance. The presence of allele *4 was associated with worse performance in a few executive tasks. APOE *3*3 was associated with overall severe dysfunction on cognitive performance. In young individuals with nontreated BD-type I, APOE may predict cognitive performance. Further and larger studies on APOE and cognition in BD are required to clarify whether APOE is a BD cognitive endophenotype.

Analysis of patellar stabilizers muscles and patellar kinematics in anterior knee pain subjects

Patella stabilizer muscle response and patellar kinematics were evaluated in 19 women with anterior knee pain (AKP) and 20 healthy women during maximum voluntary isometric contraction (MVIC) with the knee positioned at 15 degrees, 30 degrees and 45 degrees flexion during open (OKC) and closed (CKC) kinetic chain exercises. Patellar kinematics was evaluated through patellar tilt and displacement, and the electrical activity of patellar stabilizers through the root mean square normalized during MVIC and OKC with the knee at 90 degrees flexion. Data revealed that the vastus medialis oblique muscle (VMO) was more active in the control group compared to the AKP group during OKC exercises with the knee at 45 degrees flexion. However, no difference in the patellar kinematics was observed between these groups; nevertheless, the correlation between these parameters also showed, with the knee at 45 degrees flexion, that lateral patellar tilt increase was associated with a reduction in the activity of lateral patellar stabilizers in the control group and with an increase in the VMO activity in the AKP group. In conclusion, electrical activity is an important factor in evaluating AKP and in AKP treatment evolution. (C) 2010 Elsevier Ltd. All rights reserved.

Hyperbaric oxygen on the healing of ischemic colonic anastomosis - an experimental study in rats

The aim of the present study was to evaluate the effect of hyperbaric oxygen therapy (HBO(2)) on the healing process of ischemic colonic anastomoses in rats Forty Wistar rats were divided into four groups control (Group I), control and HBO(2) (Group 11), ischemia (Group III), ischemia and HBO(2) (Group IV) Ischemia was achieved by clamping four centimeters of the colonic arcade On the eighth therapy day, the anastomotic region was removed for quantification of hydroxyproline and immunohistochemical determination of metalloproteinases 1 and 9 (MMP1,MMP9) The immunohistochemical studies showed significantly larger metalloproteinase-labeled areas in Group IV compared with Group III for both MMP1 and MMP9 (p<001) This finding points to a higher remodeling activity of the anastomoses in this experimental group Additionally, animals subjected to hyperbaric oxygen therapy showed both a reduction in interstitial edema and an increase in hydroxyproline concentrations [at the anastomotic site] Therefore, we conclude that HBO(2) is indeed beneficial in anastomotic ischemia

IGFR-I expression and structural analysis of the hard palatine mucosa in an ethanol-drinking rat strain (UChA and UChB)

The study analyzed the effects of chronic alcohol ingestion on the ultrastructure of the lining epithelium of the hard palatine mucosa of rats UChA and UChB (lines with voluntary alcohol consumption) in order to contribute to the understanding of the consequences of alcohol abuse for the morphology of the digestive system. Thirty female adult animals aged 120 days were divided into three experimental groups. (1) Ten UChA rats (genetically low ethanol consumer) with voluntary intake of 10% v/v (5.45 g/kg/day) ethanol solution and water. (2) Ten UChB (genetically high ethanol consumer) rats with voluntary intake of 10% v/v (7.16 g/kg/day) ethanol solution and water. (3) Ten Wistar rats with voluntary ad libitum water intake (control group). Both groups received Nuvital pellets ad libitum. The IGFR-I expression was intense in both experimental groups. The epithelial cells of the alcoholic rats UChA and UChB showed many alterations such as the presence of lipid droplets, altered nuclei, nuclei in corneum layer and disrupted mitochondria. It was concluded that ethanol intake induces ultrastructural lesions in the hard palatine mucosa. (C) 2011 Elsevier Ltd. All rights reserved.

Chronic Acetonemia Alters Liver Oxidative Balance and Lipid Content in Rats. A Model of Nash?

Acetone is considered to be a substance that can disturb cellular oxidative status, being also associated with the production of glucose during its metabolization. The objective of the present study was to determine the effects of chronic treatment with acetone in oxidative stress and metabolic parameters in rats. Twenty male Wistar rats were divided into two groups: control (CG) and chronic acetone group (CAG). After 28 days of acetone ingestion in a 5% aqueous solution (CAG) or water (CG) the animals were euthanized and urine, plasma and liver were collected for the determination of acetone, glucose, lipemia, hepatic fat, malondialdehyde (MDA), reduced glutathione (GSH), and vitamin E. As expected, urinary and plasma acetone levels were higher in CAG. There was no difference in hepatic MDA values between groups, whereas hepatic GSH was lower in CAG than in CG and hepatic vitamin E was higher in CAG than in CG. There was also an increase in glycemia, cholesterolemia and hepatic fat in CAG compared to CG. Chronic treatment with a 5% acetone solution produced an increase in acetonemia that was able to promote changes in hepatic oxidative metabolism and in lipid content in rats similar to those observed in nonalcoholic steatohepatitis.

Combining two potential causes of metalloproteinase secretion causes abdominal aortic aneurysms in rats: a new experimental model

P>Progress in understanding the pathophysiology of abdominal aortic aneurysms (AAA) is dependent in part on the development and application of effective animal models that recapitulate key aspects of the disease. The objective was to produce an experimental model of AAA in rats by combining two potential causes of metalloproteinase (MMP) secretion: inflammation and turbulent blood flow. Male Wistar rats were randomly divided in four groups: Injury, Stenosis, Aneurysm and Control (40/group). The Injury group received a traumatic injury to the external aortic wall. The Stenosis group received an extrinsic stenosis at a corresponding location. The Aneurysm group received both the injury and stenosis simultaneously, and the Control group received a sham operation. Animals were euthanized at days 1, 3, 7 and 15. Aorta and/or aneurysms were collected and the fragments were fixed for morphologic, immunohistochemistry and morphometric analyses or frozen for MMP assays. AAAs had developed by day 3 in 60-70% of the animals, reaching an aortic dilatation ratio of more than 300%, exhibiting intense wall remodelling initiated at the adventitia and characterized by an obvious inflammatory infiltrate, mesenchymal proliferation, neoangiogenesis, elastin degradation and collagen deposition. Immunohistochemistry and zymography studies displayed significantly increased expressions of MMP-2 and MMP-9 in aneurysm walls compared to other groups. The haemo-dynamic alterations caused by the stenosis may have provided additional contribution to the MMPs liberation. This new model illustrated that AAA can be multifactorial and confirmed the key roles of MMP-2 and MMP-9 in this dynamic remodelling process.