Comparison of Measurement Techniques and Response Criteria for MR Imaging Follow-up in Adult Primary Central Nervous System Lymphoma.

BACKGROUND AND PURPOSE: Current guidelines proposed for the measurement of primary central nervous system lymphoma in 2005 have indicated that unidimensional and bidimensional measurements may be used, using the same threshold for response categorization, because no clinical study has evaluated the agreement among the measurement techniques. Hence, our study assessed the agreement among different measurements. MATERIALS AND METHODS: In this retrospective study, primary central nervous system lymphoma lesions were measured with different techniques (longest 1D, axial 1D, 2D, 3D, and the Response Evaluation Criteria in Solid Tumor) on consecutive MR images. Intra- and interobserver correlations were calculated with intraclass correlation coefficients. Correlations between raw measurements and variations in size compared with baseline were evaluated with the Spearman rank correlation, and agreement among response categories was evaluated. RESULTS: A total of 304 examinations obtained in 40 patients was assessed. The intraobserver intraclass correlation coefficient for 3D, 2D, and longest 1D were ≥0.993. The interobserver intraclass correlation coefficient was ≥0.967. The correlations in raw measurements and size variation in comparison with 3D were respectively; 0.99 and 0.98 for 2D; 0.94 and 0.92 for longest 1D; 0.94 and 0.83 for axial 1D; and 0.90 and 0.79 for Response Evaluation Criteria in Solid Tumor. With 20%-30% and 25%-50% thresholds for unidimensional techniques, response categorizations were 95% and 95% for 2D, 92.5% and 90% for the longest 1D, 87.5% and 82.5% for axial 1D, and 90% and 85% for the Response Evaluation Criteria in Solid Tumor. CONCLUSIONS: Both longest 1D and 2D demonstrated excellent correlations with 3D measurements. The longest 1D could be used for the follow-up of primary central nervous system lymphoma. If unidimensional measurements were used, 20% and 30% cutoffs should be used for defining response categorization instead of the current guidelines.

Nanoscale Structure, Dynamics, and Aging Behavior of Metallic Glass Thin Films.

Scanning tunnelling microscopy observations resolve the structure and dynamics of metallic glass Cu100-xHfx films and demonstrate scanning tunnelling microscopy control of aging at a metallic glass surface. Surface clusters exhibit heterogeneous hopping dynamics. Low Hf concentration films feature an aged surface of larger, slower clusters. Argon ion-sputtering destroys the aged configuration, yielding a surface in constant fluctuation. Scanning tunnelling microscopy can locally restore the relaxed state, allowing for nanoscale lithographic definition of aged sections.

Exploratory study of the effect of brain tumors on the default mode network.

Resting state functional magnetic resonance imaging (RS-fMRI) is a popular method of visualizing functional networks in the brain. One of these networks, the default mode network (DMN), has exhibited altered connectivity in a variety of pathological states, including brain tumors. However, very few studies have attempted to link the effect of tumor localization, type and size on DMN connectivity. We collected RS-fMRI data in 73 patients with various brain tumors and attempted to characterize the different effects these tumors had on DMN connectivity based on their location, type and size. This was done by comparing the tumor patients with healthy controls using independent component analysis (ICA) and seed based analysis. We also used a multi-seed approach described in the paper to account for anatomy distortion in the tumor patients. We found that tumors in the left hemisphere had the largest effect on DMN connectivity regardless of their size and type, while this effect was not observed for right hemispheric tumors. Tumors in the cerebellum also had statistically significant effects on DMN connectivity. These results suggest that DMN connectivity in the left side of the brain may be more fragile to insults by lesions.

Skeletal Muscle Response to Endurance Training in IL-6-/- Mice.

We examined effects of moderate-intensity endurance training on muscle COX/CS activities and V'O2max in control WT and IL-6(-/-) mice. Animals were exercised for 10 weeks on treadmill for 1 h, 5 days a week at velocity of 6 m·min(-1) which was increased by 0.5 m·min(-1) every 2 weeks up to 8 m·min(-1) . Training triggered an increase of enzyme activities in soleus muscle of WT mice (COX: 480.3±8.9 U·g(-1) in sedentary group vs. 773.3±62.6 U·g(-1) in trained group, P<0.05 and CS: 374.0±6.0 U·g(-1) in sedentary group vs. 534.2±20.5 U·g(-1) in trained group, P<0.01, respectively) whereas no changes were observed in soleus of IL6(-/-) mice. Moreover, in mixed gastrocnemius muscle of trained IL-6(-/-) mice enzyme activities tended to be lower (COX: 410.7±48.4 U·g(-1) for sedentary vs. 277.0±36.5 U·g(-1) for trained group and CS: 343.8±24.6 U·g(-1) for sedentary vs. 251.7±27.1 U·g(-1) for trained group). No changes in V'O2max were observed in WT and IL-6(-/-) mice after training. Concluding, moderate-velocity endurance training-induced increase in COX and CS activities in muscles of WT mice only which suggests that IL-6 regulates training-induced skeletal muscle responses to exercise.

A memory-based foraging tactic reveals an adaptive mechanism for restricted space use.

The restricted area of space used by most mobile animals is thought to result from fitness-rewarding decisions derived from gaining information about the environment. Yet, assessments of how animals deal with uncertainty using memory have been largely theoretical, and an empirically derived mechanism explaining restricted space use in animals is still lacking. Using a patch-to-patch movement analysis, we investigated predictions of how free-ranging bison (Bison bison) living in a meadow-forest matrix use memory to reduce uncertainty in energy intake rate. Results indicate that bison remembered pertinent information about location and quality of meadows, and they used this information to selectively move to meadows of higher profitability. Moreover, bison chose profitable meadows they had previously visited, and this choice was stronger after visiting a relatively poor quality meadow. Our work demonstrates a link between memory, energy gains and restricted space use while establishing a fitness-based integration of movement, cognitive and spatial ecology.

Altered skeletal muscle mitochondrial biogenesis but improved endurance capacity in trained OPA1-deficient mice.

The role of OPA1, a GTPase dynamin protein mainly involved in the fusion of inner mitochondrial membranes, has been studied in many cell types, but only a few studies have been conducted on adult differentiated tissues such as cardiac or skeletal muscle cells. Yet OPA1 is highly expressed in these cells, and could play different roles, especially in response to an environmental stress like exercise. Endurance exercise increases energy demand in skeletal muscle and repeated activity induces mitochondrial biogenesis and activation of fusion-fission cycles for the synthesis of new mitochondria. But currently no study has clearly shown a link between mitochondrial dynamics and biogenesis. Using a mouse model of haploinsufficiency for the Opa1 gene (Opa1(+/-)), we therefore studied the impact of OPA1 deficiency on the adaptation ability of fast skeletal muscles to endurance exercise training. Our results show that, surprisingly, Opa1(+/-) mice were able to perform the same physical activity as control mice. However, the adaptation strategies of both strains after training differed: while in control mice mitochondrial biogenesis was increased as expected, in Opa1(+/-) mice this process was blunted. Instead, training in Opa1(+/-) mice led to an increase in endurance capacity, and a specific adaptive response involving a metabolic remodelling towards enhanced fatty acid utilization. In conclusion, OPA1 appears necessary for the normal adaptive response and mitochondrial biogenesis of skeletal muscle to training. This work opens new perspectives on the role of mitochondrial dynamics in skeletal muscle cells and during adaptation to stress.

The blood-brain barrier: its influence in the treatment of brain tumors metastases.

Brain metastases represent the most common intracranial tumors in the adults. Its incidence outnumbers that of primary brain tumors by a tenfold factor. Estimated cumulative incidence is between 10 to 20% of all cancer patients, which would represent over 170 000 new cases in the US. Typically, patients with multiple brain metastases are exposed to whole brain radiation therapy, as a palliative measure. Resulting median survival improvement is modest, ranging from 3 to 5 months. This survival has not been altered despite 3 decades of clinical research aiming at improving outcome of these patients. The role of standard chemotherapy in the treatment of brain metastases has always been marginal, as the penetration of chemotherapy beyond the BBB (blood-brain barrier) is considered limited. Whereas the BBB is universally recognized as a physiological entity, its role in the treatment of brain metastases remains controversial. Metastatic lesions often depict a homogeneous intense enhancement on either CT or MRI, thus implying that the brain tumor barrier (BTB) is breached. Although there is no doubt that the BBB and BTB suffer from variable degrees of breach in integrity in the presence of malignant brain tumors, impediment to drug delivery remains, and strategy to optimize delivery must be considered if one is to really impact patient � s outcome in the treatment of these diseases. The intended purpose of this paper is to review current data on the role of the BBB in the treatment of CNS metastatic disease.

Effect of simulated masticatory loading on the retention of stud attachments for implant overdentures.

This study assessed the effect of simulated mastication on the retention of two stud attachment systems for 2-implants overdentures. Sixteen specimens, each simulating an edentulous ridge with implants and an overdenture were divided into two groups, according to the attachment system: Group I (Nobel Biocare ball-socket attachments) and Group II (Locator attachments). Retention forces were measured before and after 400,000 simulated masticatory loads in a customised device. Data were compared by two-way anova followed by Bonferroni test (α = 0·05). Group I presented significantly lower retention forces (Newtons) than Group II at baseline (10·6 ± 3·6 and 66·4 ± 16·0, respectively). However, differences were not significant after 400,000 loads (7·9 ± 4·3 and 21·6 ± 17·0). The number of cycles did not influence the measurements in Group I, whereas a non-linear descending curve was found for Group II. It was concluded that simulated mastication resulted in minor changes for the ball attachment tested. Nevertheless, it reduced the retention of Locator attachments to 40% of the baseline values, what suggests that mastication is a major factor associated with maintenance needs for this system.

What are the factors that predict outcome at relapse after previous esophagectomy and adjuvant therapy in high-risk esophageal cancer?

OBJECTIVES: The present study investigated factors affecting outcome at relapse after previous surgery and adjuvant chemoradiation (crt) in high-risk esophageal cancer patients. PATIENTS AND METHODS: From 1989 to 1999, we followed high-risk resected esophageal cancer patients who had completed postoperative crt therapy. Patients who relapsed with a disease-free interval of less than 3 months were treated with palliative crt when appropriate. Patients with a disease-free interval of 3 months or more were treated with best supportive care. Post-recurrence survival was estimated using the Kaplan-Meier technique, and statistical comparisons were made using log-rank chi-square tests and Cox regression. RESULTS: Of the 69 patients treated with adjuvant crt after esophagectomy, 46 experienced recurrence. Median time to relapse was 28 months (range: 0.1-40 months). Among the 46 relapsed patients, median age was 61 years (range: 37-82 years), and 42 were men. At the initial staging, 44 of 46 were node-positive; 31 of 46 had adenocarcinoma. In 33 of 46, post-esophagectomy resection margins were clear. Median follow-up after recurrence was 30.5 months (range: 1.3-100 months). Median overall survival after recurrence was 5.8 months, and the 12-month, 24-month, and 36-month survival rates were 20%, 10%, and 5% respectively. Of the prognostic factors analyzed, only resection margin status and interval to recurrence were statistically significant for patient outcome in univariate and multivariate analysis. Patients who had positive resection margins and who relapsed 12 or fewer months after surgery and adjuvant crt had a median post-recurrence overall survival of 0.85 months as compared with 6.0 months in other patients (more than 12 months to relapse, or negative resection margins, or both; log-rank p = 0.003). CONCLUSIONS: Resection margin status and interval to disease relapse are significant independent prognostic factors for patient outcome after adjuvant crt therapy.

Postoperative extended-volume external-beam radiation therapy in high-risk esophageal cancer patients: a prospective experience.

BACKGROUND AND PURPOSE: Extended-volume external-beam radiation therapy (RT) following esophagectomy is controversial. The present prospective study evaluates the feasibility of extended-volume RT treatment in high-risk esophagectomy patients with a cervical anastomosis receiving postoperative combined chemoradiation therapy. PATIENTS AND METHODS: From 2001 to 2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study to evaluate the adverse effects of extended-volume RT. Postoperative management was carried out at London Regional Cancer Program. Eligibility criteria were pathology-proven esophageal malignancy (T3-4, N0-1), disease amenable to surgical resection, and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous RT were excluded. All 15 study patients received 4 cycles of 5-fluorouracil-based chemotherapy. External-beam RT was conducted using conformal computed tomography planning, with multi-field arrangement tailored to the pathology findings, with coverage of a clinical target volume encompassing the primary tumour bed and the anastomotic site in the neck. The radiation therapy dose was 50.40 Gy at 1.8 Gy per fraction. The RT was delivered concurrently with the third cycle of chemotherapy. The study outcomes-disease-free survival (DFS) and overall survival (OS)-were calculated by the Kaplan-Meier method. Treatment-related toxicities were assessed using the U.S. National Cancer Institute's Common Toxicity Criteria. RESULTS: The study accrued 10 men and 5 women of median age 64 years (range: 48-80 years) and TNM stages T3N0 (n = 1), T2N1 (n = 2), T3N1 (n = 11), and T4N1 (n = 1). Histopathology included 5 adenocarcinomas and 10 squamous-cell carcinomas. Resection margins were clear in 10 patients. The median follow-up time was 19 months (range: 3.5-53.4 months). Before radiation therapy commenced, delay in chemotherapy occurred in 20% of patients, and dose reduction was required in 13.3%. During the concurrent chemoradiation therapy phase, 20% of the patients experienced chemotherapy delay, and 6.6% experienced dose reduction. No patient experienced treatment-related acute and chronic esophagitis above grade 2. Disease recurred in 40% of the patients (6/15), and median time to relapse was 24 months. No tumour recurred at the anastomotic site. The median DFS was 23 months, and the median OS was 21 months. CONCLUSIONS: Extended-volume external-beam RT encompassing the tumour bed and the anastomotic site is feasible and safe for high-risk T3-4, N0-1 esophageal cancer patients after esophagectomy.

Stimulus specific changes of energy metabolism in hypertrophied heart.

Cardiac energy metabolism is a determinant of the response to hypertrophic stimuli. To investigate how it responds to physiological or pathological stimuli, we compared the energetic status in models of hypertrophy induced by physiological stimuli (pregnancy or treadmill running) and by pathological stimulus (spontaneously hypertensive rats, SHR) in 15 week-old female rats, leading to a 10% cardiac hypertrophy. Late stage of compensated hypertrophy was also studied in 25 week-old SHR (35% of hypertrophy). Markers of cardiac remodelling did not follow a unique pattern of expression: in trained rats, only ANF was increased; in gravid rats, calcineurin activation and BNP expression were reduced while beta-MHC expression was enhanced; all markers were clearly up-regulated in 25 week-old SHR. Respiration of permeabilized fibers revealed a 17% increase in oxidative capacity in trained rats only. Mitochondrial enzyme activities, expression of the master regulator PGC-1alpha and mitochondrial transcription factor A, and content of mitochondrial DNA were not consistently changed, suggesting that compensated hypertrophy does not involve alterations of mitochondrial biogenesis. Mitochondrial fatty acid utilization tended to increase in trained rats and decreased by 14% in 15 week-old SHR. Expression of markers of lipid oxidation, PPARalpha and its down-stream targets MCAD and CPTI, was up-regulated after training and tended to decrease in gravid and 15 week-old SHR rats. Taken together these results show that there is no univocal pattern of cardiac adaptation in response to physiological or pathological hypertrophic stimuli, suggesting that other factors could play a role in determining adaptation of energy metabolism to increased workload.

Preliminary characterization and biological reduction of putative biogenic iron oxides (BIOS) from the Tonga-Kermadec Arc, southwest Pacific Ocean.

Sediment samples were obtained from areas of diffuse hydrothermal venting along the seabed in the Tonga sector of the Tonga-Kermadec Arc, southwest Pacific Ocean. Sediments from Volcano 1 and Volcano 19 were analyzed by X-ray diffraction (XRD) and found to be composed primarily of the iron oxyhydroxide mineral, two-line ferrihydrite. XRD also suggested the possible presence of minor amounts of more ordered iron (hydr)oxides (including six-line ferrihydrite, goethite/lepidocrocite and magnetite) in the biogenic iron oxides (BIOS) from Volcano 1; however, Mössbauer spectroscopy failed to detect any mineral phases more crystalline than two-line ferrihydrite. The minerals were precipitated on the surfaces of abundant filamentous microbial structures. Morphologically, some of these structures were similar in appearance to the known iron-oxidizing genus Mariprofundus spp., suggesting that the sediments are composed of biogenic iron oxides. At Volcano 19, an areally extensive, active vent field, the microbial cells appeared to be responsible for the formation of cohesive chimney-like structures of iron oxyhydroxide, 2-3 m in height, whereas at Volcano 1, an older vent field, no chimney-like structures were apparent. Iron reduction of the sediment material (i.e. BIOS) by Shewanella putrefaciens CN32 was measured, in vitro, as the ratio of [total Fe(II)]:[total Fe]. From this parameter, reduction rates were calculated for Volcano 1 BIOS (0.0521 day(-1)), Volcano 19 BIOS (0.0473 day(-1)), and hydrous ferric oxide, a synthetic two-line ferrihydrite (0.0224 day(-1)). Sediments from both BIOS sites were more easily reduced than synthetic ferrihydrite, which suggests that the decrease in effective surface area of the minerals within the sediments (due to the presence of the organic component) does not inhibit subsequent microbial reduction. These results indicate that natural, marine BIOS are easily reduced in the presence of dissimilatory iron-reducing bacteria, and that the use of common synthetic iron minerals to model their reduction may lead to a significant underestimation of their biological reactivity.

Factors affecting methylmercury distribution in surficial, acidic, base-metal mine tailings.

The most toxic form of Hg commonly of concern in the environment is methylmercury (MeHg), as it accumulates in living tissues and bioconcentrates in food webs. Sulfide-rich metal ores are often enriched in Hg, but little is known regarding the potential for Hg methylation in acidic tailings produced from these ores. This study examined acidic tailings from four mines in northern Ontario, Canada, to determine whether they could be an important source of MeHg to downstream environments. Where sulfate reducing bacteria (SRB) were abundant and active in pH-circumneutral, unoxidized layers (Potter mine), negligible MeHg was detected. By contrast, a zone of active sulfate reduction found in the acidic, oxidizing, surficial layers of tailings from the Kidd Metsite contained the highest concentrations of MeHg in bulk tailings (12.1 nmol kg(-1) dry wt. of sediment) and porewaters (88 pM) measured in this study. Cell count estimates of SRB by the "most-probable-number" (MPN) method were low in these surficial tailings, suggesting that sulfate reducers from this environment were acidophilic and did not thrive under the pH-neutral conditions of the MPN incubations. A later study of bacterial DNA from these tailings produced evidence of a novel Deltaproteobacterium which has only previously been detected in acid mine drainage environments. Further research will be necessary to determine whether this Deltaproteobacterium is a sulfate reducer and/or an efficient Hg methylator. Surface water concentrations of MeHg did not exceed Canadian water quality guidelines at any of the sites sampled, but one site (Broulan) featured total Hg (HgT) concentrations of 838 pM in filtered samples, far in excess of recommended levels. Trends in surface water MeHg and HgT reflected corresponding values in porewaters from the same sites, indicating that concentrations of these substances in tailings influence surface water concentrations.

Mitochondrial biogenesis in fast skeletal muscle of CK deficient mice.

Creatine kinase (CK) is a phosphotransfer kinase that catalyzes the reversible transfer of a phosphate moiety between ADP and creatine and that is highly expressed in skeletal muscle. In fast glycolytic skeletal muscle, deletion of the cytosolic M isoform of CK in mice (M-CK-/-) leads to a massive increase in the oxidative capacity and of mitochondrial volume. This study was aimed at investigating the transcriptional pathways leading to mitochondrial biogenesis in response to CK deficiency. Wild type and M-CK-/- mice of eleven months of age were used for this study. Gastrocnemius muscles of M-CK-/- mice exhibited a dramatic increase in citrate synthase (+120%) and cytochrome oxidase (COX, +250%) activity, and in mitochondrial DNA (+60%), showing a clear activation of mitochondrial biogenesis. Similarly, mRNA expression of the COXI (mitochondria-encoded) and COXIV (nuclear-encoded) subunits were increased by +103 and +94% respectively. This was accompanied by an increase in the expression of the nuclear respiratory factor (NRF2alpha) and the mitochondrial transcription factor (mtTFA). Expression of the co-activator PGC-1alpha, a master gene in mitochondrial biogenesis was not significantly increased while that of PGC-1beta and PRC, two members of the same family, was moderately increased (+45% and +55% respectively). While the expression of the modulatory calcineurin-interacting protein 1 (MCIP1) was dramatically decreased (-68%) suggesting inactivation of the calcineurin pathway, the metabolic sensor AMPK was activated (+86%) in M-CK-/- mice. These results evidence that mitochondrial biogenesis in response to a metabolic challenge exhibits a unique pattern of regulation, involving activation of the AMPK pathway.

A 3D visualization tool for the design and customization of spinal braces.

A new tool was developed and validated on an X-ray dummy to allow personalized design and adjustment of spinal braces. The 3D visualization of the external trunk surface registered with the underlying 3D bone structures permits the clinicians to select pressure areas on the trunk surface for proper positioning of correcting pads inside the brace according to the patient's specific trunk deformities. After brace fabrication, the clinicians can evaluate the actual 3D patient-brace interface pressure distribution visualized simultaneously with the 3D model of the trunk in order to customize brace adjustment and validate brace design with respect to the treatment plan.

Dynamics of an Ising chain under local excitation: a scanning tunneling microscopy study of Si(100) dimer rows at 5 K.

An extension of the classical Ising model to a situation including a source of spin-flip excitations localized on the scale of individual spins is considered. The scenario is realized by scanning tunneling microscopy of the Si(100) surface at low temperatures. Remarkable details, corresponding to the passage of phasons through the tunnel junction, are detected by the STM within the short span between two atoms comprising an individual Si dimer.

Evaluation of a rapid point-of-care test for the detection of gonococcal infection among female sex workers in Benin.

OBJECTIVES: To assess the validity of the PATH (Seattle, Washington, USA) GC-Check rapid test, a point-of-care immunochromatographic strip test, in the detection of gonococcal infection among female sex workers (FSWs) in Benin. METHODS: Women consulting consecutively at two FSW-dedicated clinics in Cotonou and Porto Novo (Benin) were recruited over three, 1-month periods between October 2003 and July 2004. After written informed consent, participants were administered a short interview and underwent a speculum examination where two cervical swabs were collected (in a subset of women, a vaginal swab was also collected). One cervical swab and the vaginal swab were immediately tested with the rapid test. The other cervical swab was frozen at -20 degrees C for at most four weeks and then transported to Québec (Canada), where it was tested with the Roche Amplicor CT/NG PCR assay. Samples positive for gonococcal infection were confirmed using a 16SrRNA PCR assay. RESULTS: 1084 FSWs (median age 29 years) participated in the study, of whom 50 (4.6%) had a confirmed gonococcal infection. The sensitivity, specificity, positive and negative predictive values of the rapid test on cervical samples were 70.0% (95% confidence interval (CI) 55.4% to 82.1%), 97.2% (95% CI 96.0% to 98.1%), 54.7% and 98.5%, respectively. The sensitivity of the rapid test on vaginal swabs among 759 women (37 positives for gonococcal infection) was significantly lower than with the cervical swab (54.1%, p = 0.008), whereas the specificity was comparable (98.2%, p = 0.13). CONCLUSIONS: The PATH GC-Check test may be as efficient as a gold standard polymerase chain reaction (PCR) test for treating gonococcal infection when taking into account the proportion of women who do not return for their test results. In clinics serving populations with moderate prevalence of this infection, it could significantly reduce over-treatment compared to the syndromic approach.

Neuronal injuries induced by perinatal hypoxic-ischemic insults are potentiated by prenatal exposure to lipopolysaccharide: animal model for perinatally acquired encephalopathy.

We developed an original rat model for neonatal brain lesions whereby we explored the sequential effects of infectious and hypoxic-ischemic aggressions. We investigated the influence of combined exposure to prenatal infection with neonatal hypoxic-ischemic insult. Infectious effect was produced by administrating lipopolysaccharide (LPS) intraperitoneally to pregnant rats starting on embryonic day 17. Hypoxia-ischemia (H/I) was induced in the pups at postnatal day 1 (P1) by ligature of the right common carotid artery followed by exposure to hypoxia (8% O(2)) for 3.5 h. Animals were randomized into four groups: (1) control group: pups born to mothers subjected to intraperitoneal saline injection; (2) LPS group: pups exposed in utero to LPS; (3) H/I group: pups exposed to postnatal hypoxia after ligation of the right carotid artery, and (4) H/I plus LPS group: in utero exposure to LPS followed by postnatal hypoxia after ligation of the right carotid artery. Neuropathological findings in pups examined at P3 and P8 showed that groups 2, 3, and 4 presented a pattern of neuronal injury similar to those characterized as 'selective neuronal necrosis' within the context of human perinatal encephalopathy. Neuronal cellular injuries were particularly seen in the neocortex, mainly in parasagittal areas. The extent of neuronal cell injury in the brain of rats exposed to postnatal H/I was significantly increased by antenatal exposure to LPS. This animal model provides an experimental means to explore the respective roles of anoxic and infectious components in the pathogenesis of perinatal brain lesions and consequent cerebral palsy.

Differential effects of thyroid hormones on energy metabolism of rat slow- and fast-twitch muscles.

Thyroid hormone (TH) is an important regulator of mitochondrial content and activity. As mitochondrial content and properties differ depending on muscle-type, we compared mitochondrial regulation and biogenesis by T3 in slow-twitch oxidative (soleus) and fast-twitch mixed muscle (plantaris). Male Wistar rats were treated for 21 to 27 days with T3 (200 microg/kg/day). Oxidative capacity, regulation of mitochondrial respiration by substrates and phosphate acceptors, and transcription factors were studied. In soleus, T3 treatment increased maximal oxygen consumption (Vmax) and the activities of citrate synthase (CS) and cytochrome oxidase (COX) by 100%, 45%, and 71%, respectively (P < 0.001), whereas in plantaris only Vmax increased, by 39% (P < 0.01). ADP-independent respiration rate was increased in soleus muscle by 216% suggesting mitochondrial uncoupling. Mitochondrial substrate utilization in soleus was also influenced by T3, as were mitochondrial enzymes. Lactate dehydrogenase (LDH) activity was elevated in soleus and plantaris by 63% and 11%, respectively (P < 0.01), and soleus creatine kinase was increased by 48% (P < 0.001). T3 increased the mRNA content of the transcriptional co-activator of mitochondrial genes, PGC-1alpha, and the I and IV COX subunits in soleus. The muscle specific response to thyroid hormones could be explained by a lower content of TH receptors in plantaris than soleus. Moreover, TRalpha mRNA level decreased further after T3 treatment. These results demonstrate that TH has a major effect on mitochondrial content, regulation and coupling in slow oxidative muscle, but to a lesser extent in fast muscle, due to the high expression of TH receptors and PGC-1alpha transcription factor.