Changes in serum enzyme activities after injection of bupivacaine into rat tibialis anterior

1996 ◽  
Vol 81 (2) ◽  
pp. 876-884 ◽  
Author(s):  
K. Nosaka

This study investigated the time course of changes in serum creatine kinase (CK), aspartate aminotransferase (AST), and alanine amino-transferase (ALT) activities after intramuscular injection of bupivacaine into the tibialis anterior (TA) of rats. Morphological changes in muscle cells, relationships between the amount of increase in the enzyme activities and the muscle mass damaged, and responses of serum enzymes to additional injections of bupivacaine hydrochloride (BPVC) were also examined. Adult male Wistar rats (24 wk) were placed into one of four groups. Group A (n = 7) was a control, and no injection was applied. Saline solution (0.5 ml of 0.9%) was injected into the right TA for group B (n = 5). BPVC (0.5 ml of 0.5%) was injected into the right TA for group C (n = 9) and into both the right and left TA for group D (n = 9). No increases in CK, AST, and ALT were observed for groups A and B. After BPVC injection, groups C and D showed significant (P < 0.01) increases in serum enzyme activities. CK peaked 4 h after BPVC injection, and AST and ALT peaked 12 h postinjection, then returned to the baseline by the time infiltration of mononuclear cells into the damaged muscle cells progressed. The amount of enzyme increase was significantly larger (P < 0.01) for group D compared with group C. Injection of BPVC into the right then into the left TA 4 h later displayed a bipolar response, and the second injection into the TA 12 wk after the first injection resulted in smaller increase in serum enzyme activities. It appeared that increases in serum enzyme activities reflected muscle damage; however, changes in enzymes occurred in the early stage of myonecrosis.

2020 ◽  
Vol 5 (4) ◽  
pp. 2473011420S0008
Author(s):  
Jianying Zhang ◽  
Feng Li ◽  
Kentaro Onishi ◽  
MaCalus V. Hogan ◽  
James HC Wang

Category: Basic Sciences/Biologics; Sports Introduction/Purpose: Tendinopathy is a debilitating tendon disorder that affects millions of Americans and costs billions of healthcare dollars every year. Mechanical overloading is considered to cause the development of tendinopathy, but the underlying molecular mechanisms of tendinopathy remain unclear. High mobility group box-1 (HMGB1), an upstream potent inflammatory mediator, has been identified in high levels in early stage tendinopathy patients [1]. However, whether HMGB1 mediates tendinopathy development due to mechanical overloading is completely unknown. Metformin (Met), a hypoglycemic drug commonly used for the treatment of type II diabetes, has shown to inhibit the activity of HMGB1 via binding the acidic tail of HMGB1 [2]. In this study, we tested the hypothesis that Met prevents mechanical overloading-induced tendinopathy by inhibiting HMGB1. Methods: A total of 24 mice were divided into 4 groups and treated for 24 weeks as follows: Group 1 (Cage) with cage activities; Group 2 (Met) received daily IP injection of metformin (50 mg/kg body weight); Group 3 (ITR) ran on treadmill at 15 meters/min for 3 h/ day, 5 days a week; Group 4 (ITR+Met) ran the same protocol as that of ITR group but with daily IP injection of metformin. Six mice/group were sacrificed at 24 weeks and the Achilles and patellar tendon tissues were harvested. The tendons from the left legs were used for histochemical staining and the right for immunostaining. Results: We found that mechanical overloading induced HMGB1 release into tendon matrix (Fig. 1G, K, O). Metformin inhibited HMGB1 release (Fig. 1H, L, P). ITR induced degenerative tendinopathy as evidenced by the cell morphological changes from elongated shape in normal tendon (Fig. 2A, E, I, M) to round shape (Fig. 2C, G, K, O) and the accumulation of proteoglycans (Fig. 2K, O) in ITR tendon. Metformin injection inhibited ITR effect, which is shown by less round shaped cells and low proteoglycan levels found in metformin injected ITR tendons (Fig. 2D, H, L, P). ITR promoted the expression of chondrogenic markers (collagen II and SOX-9) in tendon (Fig. 3C, G, K, O), and metformin inhibited the expression of chondrogenic makers (Fig. 3D, H, L, P). Conclusion: Our study demonstrated that mechanical overloading induced degenerative changes in mouse tendons characterized by the presence of chondrocyte-like cells, accumulation of proteoglycans, high levels of chondrogenic marker SOX-9 and Collagen II expression. Administration of metformint reduced the degenerative responses in overloaded tendon and blocked the development of tendinopathy. These findings support the notion that mechanical overloading induces tendinopathy development by initiation of tendon inflammation via HMGB1, which leads to eventual tendon degeneration. Thus, metformin, a commonly prescribed and FDA approved drug that specifically inhibits HMGB1, can be used to prevent tendinopathy development due to mechanical overloading placed on the tendon.


2001 ◽  
Vol 79 (7) ◽  
pp. 1316-1321 ◽  
Author(s):  
Iwao Sato ◽  
Kiyoshi Konishi ◽  
Masataka Sunohara ◽  
Akiko Mikami

Enzyme activities in the respiratory chain, as well as the structure and numbers of mitochondria of the tibialis anterior muscle, during hibernation were compared with those of normally active muscle in the Japanese brown frog (Rana japonica). Morphological examination using an electron microscope showed that during hibernation, mitochondria were larger and longer and had clearly distinguishable outer and inner membranes with developed cristae. A significantly greater number of glycogen granules was found in the tibialis anterior muscle of hibernating frogs. The average cross-sectional area (CSA) of muscle fiber was much smaller in the samples from hibernating frogs than those from active frogs. The numbers of mitochondria per CSA were also much higher during hibernation than during active life. Measurements of the enzyme activities of succinate dehydrogenase, NADH-ferricyanide reductase, and succinate-O2 and NADH-O2 oxidoreductases showed different profiles between hibernation and active life. That is, all four activities were significantly higher during hibernation than during active life. Taken together, the results obtained suggest that the seasonal variations in the activities of respiratory-chain systems may be related to the seasonal morphological changes in muscle mitochondria in R. japonica.


VASA ◽  
2014 ◽  
Vol 43 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Weibin Huang ◽  
Weiwei Qin ◽  
Lei Lv ◽  
Haoyv Deng ◽  
Hao Zhang ◽  
...  

Background: Duffy antigen / receptor for chemokines (DARC) possesses high affinity for several chemokine subgroups of CC and CXC. Although DARC has been shown to play a role in many inflammatory diseases, its effect on chronic venous disease (CVD) remains unidentified. We explored whether the expression of DARC in skin tissue was activated under venous hypertension as well as the relationships between DARC and inflammation. Materials and methods: The inflammation in a rat model of venous hypertension caused by a femoral arterial-venous fistula (AVF) was studied. At specified intervals the pressure in the femoral veins was recorded within 42 days. Hindlimb skin specimens were harvested at different time points. The expressions of DARC, interleukin-8 (IL-8), and monocyte chemotactic protein-1 (MCP-1) in skin tissue were examined. Mononuclear cells infiltrated in skin tissue were detected. Results: Femoral venous pressures in AVF groups increased significantly at different time points (P < 0.01). DARC was expressed in skin tissue and its expression level increased significantly in AVF groups from the 7nd day on and was enhanced in a time-dependent manner within 42 days (P < 0.05). Meanwhile, both MCP-1 and IL-8 had higher levels, accompanied by increased mononuclear cells infiltrating into skin tissue (P < 0.05). Conclusions: A rat AVF model which can maintain venous hypertension for at least 42 days is competent for researching the pathogenesis of CVD. DARC, which plays a role in the inflammation of skin tissue under venous hypertension, may become a new molecular target for diagnosis and treatment of CVD at a very early stage.


Author(s):  
Jochen Seitz ◽  
Katharina Bühren ◽  
Georg G. von Polier ◽  
Nicole Heussen ◽  
Beate Herpertz-Dahlmann ◽  
...  

Objective: Acute anorexia nervosa (AN) leads to reduced gray (GM) and white matter (WM) volume in the brain, which however improves again upon restoration of weight. Yet little is known about the extent and clinical correlates of these brain changes, nor do we know much about the time-course and completeness of their recovery. Methods: We conducted a meta-analysis and a qualitative review of all magnetic resonance imaging studies involving volume analyses of the brain in both acute and recovered AN. Results: We identified structural neuroimaging studies with a total of 214 acute AN patients and 177 weight-recovered AN patients. In acute AN, GM was reduced by 5.6% and WM by 3.8% compared to healthy controls (HC). Short-term weight recovery 2–5 months after admission resulted in restitution of about half of the GM aberrations and almost full WM recovery. After 2–8 years of remission GM and WM were nearly normalized, and differences to HC (GM: –1.0%, WM: –0.7%) were no longer significant, although small residual changes could not be ruled out. In the qualitative review some studies found GM volume loss to be associated with cognitive deficits and clinical prognosis. Conclusions: GM and WM were strongly reduced in acute AN. The completeness of brain volume rehabilitation remained equivocal.


2020 ◽  
Vol 32 (2) ◽  
pp. 200-206
Author(s):  
Kei Ando ◽  
Kazuyoshi Kobayashi ◽  
Masaaki Machino ◽  
Kyotaro Ota ◽  
Satoshi Tanaka ◽  
...  

OBJECTIVEThe objective of this study was to investigate the relationship between morphological changes in thoracic ossification of the posterior longitudinal ligament (T-OPLL) and postoperative neurological recovery after thoracic posterior fusion surgery. Changes of OPLL morphology and postoperative recovery in cases with T-OPLL have not been examined.METHODSIn this prospective study, the authors evaluated data from 44 patients (23 male and 21 female) who underwent posterior decompression and fusion surgery with instrumentation for the treatment of T-OPLL at our hospital. The patients’ mean age at surgery was 50.7 years (range 38–68 years). The minimum duration of follow-up was 2 years. The location of thoracic ossification of the ligamentum flavum (T-OLF), T-OLF at the OPLL level, OPLL morphology, fusion range, estimated blood loss, operative time, pre- and postoperative Japanese Orthopaedic Association (JOA) scores, and JOA recovery rate were investigated. Reconstructed sagittal multislice CT images were obtained before and at 3 and 6 months and 1 and 2 years after surgery. The basic fusion area was 3 vertebrae above and below the OPLL lesion. All parameters were compared between patients with and without continuity across the disc space at the OPLL at 3 and 6 months after surgery.RESULTSThe preoperative morphology of OPLL was discontinuous across the disc space between the rostral and caudal ossification regions on sagittal CT images in all but one of the patients. Postoperatively, these segments became continuous in 42 patients (97.7%; occurring by 6.6 months on average) without progression of OPLL thickness. Patients with continuity at 3 months had significantly lower rates of diabetes mellitus (p < 0.05) and motor palsy in the lower extremities (p < 0.01). The group with continuity also had significantly higher mean postoperative JOA scores at 3 (p < 0.01) and 6 (p < 0.05) months and mean JOA recovery rates at 3 and 6 months (both p < 0.01) after surgery.CONCLUSIONSPreoperatively, discontinuity of rostral and caudal ossified lesions was found on CT in all patients but one of this group of 44 patients who needed surgery for T-OPLL. Rigid fixation with instrumentation may have allowed these segments to connect at the OPLL. Such OPLL continuity at an early stage after surgery may accelerate spinal cord recovery.


2010 ◽  
Vol 30 (10) ◽  
pp. 1890-1896 ◽  
Author(s):  
Jan-Marcus Daniel ◽  
Wiebke Bielenberg ◽  
Philipp Stieger ◽  
Soenke Weinert ◽  
Harald Tillmanns ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pattapon Kunadirek ◽  
Chaiyaboot Ariyachet ◽  
Supachaya Sriphoosanaphan ◽  
Nutcha Pinjaroen ◽  
Pongserath Sirichindakul ◽  
...  

AbstractNovel and sensitive biomarkers is highly required for early detection and predicting prognosis of hepatocellular carcinoma (HCC). Here, we investigated transcription profiles from peripheral blood mononuclear cells (PBMCs) of 8 patients with HCC and PBMCs from co-culture model with HCC using RNA-Sequencing. These transcription profiles were cross compared with published microarray datasets of PBMCs in HCC to identify differentially expressed genes (DEGs). A total of commonly identified of 24 DEGs among these data were proposed as cancer-induced genes in PBMCs, including 18 upregulated and 6 downregulated DEGs. The KEGG pathway showed that these enriched genes were mainly associated with immune responses. Five up-regulated candidate genes including BHLHE40, AREG, SOCS1, CCL5, and DDIT4 were selected and further validated in PBMCs of 100 patients with HBV-related HCC, 100 patients with chronic HBV infection and 100 healthy controls. Based on ROC analysis, BHLHE40 and DDIT4 displayed better diagnostic performance than alpha-fetoprotein (AFP) in discriminating HCC from controls. Additionally, BHLHE40 and DDIT4 had high sensitivity for detecting AFP-negative and early-stage HCC. BHLHE40 was also emerged as an independent prognostic factor of overall survival of HCC. Together, our study indicated that BHLHE40 in PBMCs could be a promising diagnostic and prognostic biomarker for HBV-related HCC.


Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 404
Author(s):  
Gabriela de Matuoka e Chiocchetti ◽  
Leisa Lopes-Aguiar ◽  
Natália Angelo da Silva Miyaguti ◽  
Lais Rosa Viana ◽  
Carla de Moraes Salgado ◽  
...  

Cancer cachexia is a severe wasting condition that needs further study to find ways to minimise the effects of damage and poor prognosis. Skeletal muscle is the most impacted tissue in cancer cachexia; thus, elucidation of its metabolic alterations could provide a direct clue for biomarker research and be applied to detect this syndrome earlier. In addition, concerning the significant changes in the host metabolism across life, this study aimed to compare the metabolic muscle changes in cachectic tumour-bearing hosts at different ages. We performed 1H-NMR metabolomics in the gastrocnemius muscle in weanling and young adult Walker-256 tumour-bearing rats at different stages of tumour evolution (initial, intermediate, and advanced). Among the 49 metabolites identified, 24 were significantly affected throughout tumour evolution and 21 were significantly affected regarding animal age. The altered metabolites were mainly related to increased amino acid levels and changed energetic metabolism in the skeletal muscle, suggesting an expressive catabolic process and diverted energy production, especially in advanced tumour stages in both groups. Moreover, these changes were more severe in weanling hosts throughout tumour evolution, suggesting the distinct impact of cancer cachexia regarding the host’s age, highlighting the need to adopting the right animal age when studying cancer cachexia.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria D. I. Manunta ◽  
Giuseppe Lamorte ◽  
Francesca Ferrari ◽  
Elena Trombetta ◽  
Mario Tirone ◽  
...  

AbstractSARS-CoV-2 virus infection is responsible for coronavirus disease (COVID-19), which is characterised by a hyperinflammatory response that plays a major role in determining the respiratory and immune-mediated complications of this condition. While isolating peripheral blood mononuclear cells (PBMCs) from whole blood of COVID-19 patients by density gradient centrifugation, we noticed some changes in the floating properties and in the sedimentation of the cells on density medium. Investigating this further, we found that in early phase COVID-19 patients, characterised by reduced circulating lymphocytes and monocytes, the PBMC fraction contained surprisingly high levels of neutrophils. Furthermore, the neutrophil population exhibited alterations in the cell size and in the internal complexity, consistent with the presence of low density neutrophils (LDNs) and immature forms, which may explain the shift seen in the floating abilities and that may be predictive of the severity of the disease. The percentage of this subset of neutrophils found in the PBMC band was rather spread (35.4 ± 27.2%, with a median 28.8% and IQR 11.6–56.1, Welch’s t-test early phase COVID-19 versus blood donor healthy controls P < 0.0001). Results confirm the presence of an increased number of LDNs in patients with early stage COVID-19, which correlates with disease severity and may be recovered by centrifugation on a density gradient together with PBMCs.


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