Total rupture of Achilles tendon induces inflammatory response and glial activation on the spinal cord of mice.

Rupture of Achilles tendon is a common accident affecting professional and recreational athletes. Acute and chronic pain are symptoms commonly observed in patients with rupture. However, few studies have investigated whether Achilles tendon rupture is able to promote disorders in the central nervous system (CNS). Therefore, the current study aimed to evaluate nociceptive alterations and inflammatory response in the L5 lumbar segment of Balb/c mice spinal cord after Achilles tendon rupture. We found increased algesia in the paw of the ruptured group on the 7th and 14th days post-tenotomy compared with the control group. This phenomenon was accompanied by overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase-2 (NOS-2) as well as hyperactivation of astrocytes and microglia in nociceptive areas of L5 spinal cord as evidenced by intense GFAP and IBA-1 immunostaining, respectively. Biochemical studies also demonstrated increased levels of nitrite in the L5 spinal cord of tenotomized animals compared with the control group. Thus, we have demonstrated for the first time that total rupture of the Achilles tendon induced inflammatory response and nitrergic and glial activation in the CNS in the L5 spinal cord region.

Plasma signatures of Congenital Generalized Lipodystrophy patients identified by untargeted lipidomic profiling are not changed after a fat-containing breakfast meal.

BACKGROUND: The incapacity to store lipids in adipose tissue in Congenital Generalized Lipodystrophy (CGL) causes hypoleptinemia, increased appetite, ectopic fat deposition and lipotoxicity. CGL patients experience shortened life expectancy. The plasma lipidomic profile has not been characterized fully in CGL, nor has the extent of dietary intake in its modulation. The present work investigated the plasma lipidomic profile of CGL patients in comparison to eutrophic individuals at the fasted state and after a breakfast meal. METHOD: Blood samples from 11 CGL patients and 10 eutrophic controls were collected after 12 h fasting (T0) and 90 min after an ad libitum fat-containing breakfast (T90). The lipidomic profile of extracted plasma lipids was characterized by non-target liquid chromatography mass spectrometry. RESULTS: Important differences between groups were observed at T0 and at T90. Several molecular species of fatty acyls, glycerolipids, sphingolipids and glycerophospholipids were altered in CGL. All the detected fatty acyl molecular species, several diacylglycerols and one triacylglycerol species were upregulated in CGL. Among sphingolipids, one sphingomyelin and one glycosphingolipid species showed downregulation in CGL. Alterations in the glycerophospholipids glycerophosphoethanolamines, glycerophosphoserines and cardiolipins were more complex. Interestingly, when comparing T90 versus T0, the lipidomic profile in CGL did not change as intensely as it did for control participants. CONCLUSIONS: The present study found profound alterations in the plasma lipidomic profile of complex lipids in CGL patients as compared to control subjects. A fat-containing breakfast meal did not appear to significantly influence the CGL profile observed in the fasted state. Our study may have implications for clinical practice, also aiding to a deeper comprehension of the role of complex lipids in CGL in view of novel therapeutic strategies.

Phenotyping Superagers Using Resting-State fMRI.

BACKGROUND AND PURPOSE: Superagers are defined as older adults with episodic memory performance similar or superior to that in middle-aged adults. This study aimed to investigate the key differences in discriminative networks and their main nodes between superagers and cognitively average elderly controls. In addition, we sought to explore differences in sensitivity in detecting these functional activities across the networks at 3T and 7T MR imaging fields. MATERIALS AND METHODS: Fifty-five subjects 80 years of age or older were screened using a detailed neuropsychological protocol, and 31 participants, comprising 14 superagers and 17 cognitively average elderly controls, were included for analysis. Participants underwent resting-state-fMRI at 3T and 7T MR imaging. A prediction classification algorithm using a penalized regression model on the measurements of the network was used to calculate the probabilities of a healthy older adult being a superager. Additionally, ORs quantified the influence of each node across preselected networks. RESULTS: The key networks that differentiated superagers and elderly controls were the default mode, salience, and language networks. The most discriminative nodes (ORs > 1) in superagers encompassed areas in the precuneus posterior cingulate cortex, prefrontal cortex, temporoparietal junction, temporal pole, extrastriate superior cortex, and insula. The prediction classification model for being a superager showed better performance using the 7T compared with 3T resting-state-fMRI data set. CONCLUSIONS: Our findings suggest that the functional connectivity in the default mode, salience, and language networks can provide potential imaging biomarkers for predicting superagers. The 7T field holds promise for the most appropriate study setting to accurately detect the functional connectivity patterns in superagers.

Total rupture of Achilles tendon induces inflammatory response and glial activation on the spinal cord of mice

Rupture of Achilles tendon is a common accident affecting professional and recreational athletes. Acute and chronic pain are symptoms commonly observed in patients with rupture. However, few studies have investigated whether Achilles tendon rupture is able to promote disorders in the central nervous system (CNS). Therefore, the current study aimed to evaluate nociceptive alterations and inflammatory response in the L5 lumbar segment of Balb/c mice spinal cord after Achilles tendon rupture. We found increased algesia in the paw of the ruptured group on the 7th and 14th days post-tenotomy compared with the control group. This phenomenon was accompanied by overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase-2 (NOS-2) as well as hyperactivation of astrocytes and microglia in nociceptive areas of L5 spinal cord as evidenced by intense GFAP and IBA-1 immunostaining, respectively. Biochemical studies also demonstrated increased levels of nitrite in the L5 spinal cord of tenotomized animals compared with the control group. Thus, we have demonstrated for the first time that total rupture of the Achilles tendon induced inflammatory response and nitrergic and glial activation in the CNS in the L5 spinal cord region.

Altered acylated ghrelin response to food intake in congenital generalized lipodystrophy.

BACKGROUND: Patients with congenital generalized lipodystrophy (CGL) have very low levels of leptin and are described as having a voracious appetite. However, a direct comparison between CGL and eutrophic individuals is lacking, regarding both appetite parameters and acylated ghrelin, the hormone form that is active in acute food intake stimulation. The objective of the present study was to address whether and in what extent the subjective appetite parameters and acylated ghrelin response to a meal are affected in CGL individuals, in comparison to eutrophic individuals. Additionally, an obese group was included in the study, to allow the comparison between a leptin-resistant and a leptin-deficient condition on these aspects. METHODS: Eutrophic controls (EUT, n = 10), obese subjects (OB, n = 10) and CGL (n = 11) were fasted overnight and then received an ad libitum meal. Blood was collected and the visual analogue scale was applied before and 90 minutes after the meal. An additional blood sample was collected at 60 minutes for ghrelin determination. RESULTS: The CGL patients showed low fasting levels of leptin and adiponectin, dyslipidemia, and insulin resistance. The caloric intake was similar among the 3 groups. However, both CGL (p = 0.02) and OB (p = 0.04) had shorter satiation times than EUT. The CGL patients also had lower satiety time (p = 0.01) and their sensation of hunger was less attenuated by the meal (p = 0.03). Fasting acylated ghrelin levels were lower in CGL than in EUT (p = 0.003). After the meal, the levels tended to decrease in EUT but not in CGL and OB individuals. CONCLUSION: The data indicate that, although not hyperphagic, the CGL patients present appetite disturbances in relation to eutrophic individuals. Their low fasting levels of acylated ghrelin and the absence of the physiological drop after meal intake suggest a role of these disturbances in hunger attenuation and satiety but not in acute satiation.

Local treatment with ascorbic acid accelerates recovery of post-sutured Achilles tendon in male Wistar rats.

Tendon rupture is a very frequent accident involving average people and high-performance athletes. Clinical studies describe tendon recovery as a painful and slow process involving different biochemical and histological events. Ascorbic acid (AA) is a potent antioxidant as well as an important cofactor for collagen synthesis. In the current study, we evaluated if local treatment with AA is able to promote tendon repair in tenotomized rats. Animals were submitted to Achilles tendon rupture followed by surgical suture. Control and AA groups received in loco injection of saline solution (0.9% NaCl) and 30 mM AA, respectively. Histological and functional recovery of Achilles tendon tissue was evaluated at 7, 14, and 21 days post-surgery. Hematoxylin/eosin staining and collagen fluorescence analysis showed intense disarrangement of tendon tissue in the saline group. Tenotomized animals also showed hypercellularity in tendon tissue compared with non-tenotomized animals. The Achilles functional index (AFI) showed a significant decrease of tendon functionality in tenotomized animals at 7, 14, and 21 days post-surgery. AA accelerated tissue organization and the recovery of function of the Achilles tendons. The beneficial effect of AA treatment was also observed in the organization of the collagen network. Data presented in the current work showed that in loco treatment with AA accelerated the recovery of injured Achilles tendon post-surgery.

Local treatment with ascorbic acid accelerates recovery of post-sutured Achilles tendon in male Wistar rats

Tendon rupture is a very frequent accident involving average people and high-performance athletes. Clinical studies describe tendon recovery as a painful and slow process involving different biochemical and histological events. Ascorbic acid (AA) is a potent antioxidant as well as an important cofactor for collagen synthesis. In the current study, we evaluated if local treatment with AA is able to promote tendon repair in tenotomized rats. Animals were submitted to Achilles tendon rupture followed by surgical suture. Control and AA groups received in loco injection of saline solution (0.9% NaCl) and 30 mM AA, respectively. Histological and functional recovery of Achilles tendon tissue was evaluated at 7, 14, and 21 days post-surgery. Hematoxylin/eosin staining and collagen fluorescence analysis showed intense disarrangement of tendon tissue in the saline group. Tenotomized animals also showed hypercellularity in tendon tissue compared with non-tenotomized animals. The Achilles functional index (AFI) showed a significant decrease of tendon functionality in tenotomized animals at 7, 14, and 21 days post-surgery. AA accelerated tissue organization and the recovery of function of the Achilles tendons. The beneficial effect of AA treatment was also observed in the organization of the collagen network. Data presented in the current work showed that in loco treatment with AA accelerated the recovery of injured Achilles tendon post-surgery.

Microvascular Complications in Type 1 Diabetes: A Comparative Analysis of Patients Treated with Autologous Nonmyeloablative Hematopoietic Stem-Cell Transplantation and Conventional Medical Therapy.

OBJECTIVE: To explore the impact on microvascular complications, long-term preservation of residual B-cell function and glycemic control of patients with type 1 diabetes treated with autologous nonmyeloablative hematopoietic stem-cell transplantation (AHST) compared with conventional medical therapy (CT). RESEARCH DESIGN AND METHODS: Cross-sectional data of patients treated with AHST were compared with patients who received conventional therapy from the Brazilian Type 1 Diabetes Study Group, the largest multicenter observational study in type 1 diabetes mellitus in Brazil. Both groups of patients had diabetes for 8 years on average. An assessment comparison was made on the presence of microvascular complications, residual function of B cell, A1c, and insulin dose of the patients. RESULTS: After a median of 8 years of diagnosis, none of the AHST-treated patients (n = 24) developed microvascular complications, while 21.5% (31/144) had at least one (p < 0.005) complication in the CT group (n = 144). Furthermore, no case of nephropathy was reported in the AHST group, while 13.8% of CT group (p < 0.005) developed nephropathy during the same period. With regard of residual B-cell function, the percentage of individuals with predicted higher C-peptide levels (IDAA1C ≤ 9) was about 10-fold higher in the AHST group compared with CT (75 vs. 8.3%) (p < 0.001) group. Among AHST patients, 54.1% (13/24) had the HbA1c < 7.0 compared with 13.1% in the CT (p < 0.001) group. CONCLUSION: Patients with newly diagnosed type 1 diabetes treated with AHST presented lower prevalence of microvascular complications, higher residual B-cell function, and better glycemic control compared with the CT group.

Periodic neural activity induced by network complexity.

We study a model for neural activity on the small-world topology of Watts and Strogatz and on the scale-free topology of Barabási and Albert. We find that the topology of the network connections may spontaneously induce periodic neural activity, contrasting with nonperiodic neural activities exhibited by regular topologies. Periodic activity exists only for relatively small networks and occurs with higher probability when the rewiring probability is larger. The average length of the periods increases with the square root of the network size.