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Biomedical subjects

Kuo-Sheng Hung

Publications and source records attributed to Kuo-Sheng Hung.

18 recordsLinked to original sources
PubMed2007

Gene transfer of insulin-like growth factor-I providing neuroprotection after spinal cord injury in rats.

OBJECT: Insulin-like growth factor-I (IGF-I) has been shown to be a potent neurotrophic factor that promotes the growth of projection neurons, dendritic arborization, and synaptogenesis. Its neuroprotective roles may be coordinated by activation of Akt, inhibition of glycogen synthase kinase-3beta (GSK-3beta), and thus inhibition of tau phosphorylation. The authors investigated the role and mechanism of IGF-I gene transfer after spinal cord injury (SCI). METHODS: Studies were performed in 40 male Sprague-Dawley rats after spinal cord hemisection. The authors conducted hydrodynamics-based gene transfection in which an IGF-I plasmid was rapidly injected into the rat's tail vein 30 minutes after SCI. The animals were randomly divided into four groups: Group I, sham operated; Group II, SCI treated with pCMV-IGF-I gene; Group III, SCI treated with vehicle pCMV-LacZ gene; and Group IV, SCI only. The results showed that IGF-I gene transfer promoted motor recovery, antiinflammatory responses, and antiapoptotic effects after SCI. Using techniques of Western blotting and immunohistochemistry, the authors assessed the mechanism of IGF-I gene transfer after SCI in terms of activation of Akt, inhibition of GSK-3beta, attenuation of p35, and inhibition of tau phosphorylation. Moreover, they found that IGF-I gene transfer could block caspase-9 cleavage, increase Bcl-2 formation, and thus inhibit apoptosis after SCI. CONCLUSIONS: The intravenous administration of IGF-I after SCI activated Akt, attenuated GSK-3beta, inhibited p35 activation, diminished tau hyperphosphorylation, ended microglia and astrocyte activation, inhibited neuron loss, and significantly improved neurological dysfunction. Furthermore, IGF-I attenuated caspase-9 cleavage, increased Bcl2, and thus inhibited apoptosis after SCI.

Animals↗
PubMed2006

The effect of insulin-like growth factor-I on hepatocyte apoptosis after bile duct ligation in rat.

Obstructive jaundice may promote bacterial overgrowth and altered intestinal barrier function, with resultant increased translocation of endotoxin to the liver, amd thus may potentiate the phenomenon of hepatocyte apoptosis. Exogenous administration of insulin-like growth factor-I (IGF-I) has been shown to enhance mucosal adaptation after small bowel resection in rats and also to accelerate repair of small intestinal mucosa after damage by the chemotherapy drug methotrexate. The aim of the current study was to determine the effect of exogenous IGF-I administration on hepatocyte apoptosis after bile duct ligation in rat. Male Sprague-Dawley rats weighing 250-300 g were randomized to three groups (n=6 in each group). Group 1 (control; C) underwent sham operation and was simultaneously treated with the same amount of normal saline. Group 2 (obstructive jaundice; OB) underwent common bile duct ligation without other manipulation. Group 3 (obstructive jaundice with IGF-I; OBIGF-I) underwent common bile duct ligation and simultaneous treatment with recombinant human IGF-I (a total dose of 1 mg in each rat, divided into six administrations; about 1 mg/kg/day). After 3 days, liver tissue was harvested and immediately snap-frozen in liquid nitrogen for histopathologic analysis and apoptosis measurements. Compared with the sham operation group (C), increased hepatocyte apoptosis (P < 0.001) and ductular proliferation (P < 0.001) occurred after common bile duct ligation (OB). After administration of IGF-I (OBIFG-I), the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (OB) were significantly diminished (P < 0.001 and P < 0.001, respectively). There was no significant difference in hepatocyte apoptosis (P=0.925) or ductular proliferation (P=0.385) between the sham control group (C) and the OBIGF-I group. Increased hepatocyte apoptosis (P < 0.001) and ductular proliferation (P < 0.001) occurred after common bile duct ligation (OB). After administration of IGF-I (OBIFG-I), the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (OB) were significantly diminished (P < 0.001 and P < 0.001, respectively).

Animals↗
PubMed2006

Evaluation of MMP3 and TIMP1 as candidate genes for high myopia in young Taiwanese men.

PURPOSE: We studied the relationship between high myopia and the MMP3 and TIMP1 genes. DESIGN: Case-control study. METHODS: We enrolled 150 high myopic individuals (< or = -6 diopters) and 262 controls (> or = -1.5 diopters) initially, and another 216 cases and 474 controls were enrolled for genotyping promising polymorphisms for replication. Thirteen polymorphisms were genotyped in the initial data. Logistic regression was used to test for genetic effects. Subset analyses were performed according to the education level and family history. RESULTS: There was no significant association between any polymorphism and high myopia in the initial data. Among the highly educated subjects, the 5A/6A polymorphism at the MMP3 gene suggested a potential relationship with high myopia, and it was genotyped in the follow-up samples. However, this polymorphism failed to show any significant results in the overall subjects. CONCLUSIONS: The two genes may not play a crucial role for high myopia in young Taiwanese men.

Adolescent↗
PubMed2006

Post-traumatic hemifacial spasm.

We report an early-onset post-traumatic hemifacial spasm and discuss possible aetiology. A 20-year-old man was admitted to our hospital for observation because of an injury to the right frontotemporal region, resulting in drowsiness. On the second day in hospital, he developed peripheral paresis of the facial nerve on the right, followed by hemifacial spasm on the same side. He improved after corticosteroid treatment, and was discharged one week later almost completely recovered. The neuroradiology and clinical response suggest that the patient's hemifacial spasm was due to hyperexcitability of the facial nerve nucleus induced by a haematoma in the lower central pons.

Adult↗
PubMed2006

Bone morphogenetic protein gene therapy using a fibrin scaffold for a rabbit spinal-fusion experiment.

OBJECTIVE: To observe the feasibility of using fibrin gel as a scaffold during rabbit spinal fusion with rat kidney cells carrying bone morphogenetic protein-2 (BMP-2) expression vector. METHODS: Normal Rattusnorvegicus (rat) kidney (NRK) cells were transfected with pCMV-BMP2 vectors by using a nonviral reagent (FuGENE6), following which the transfected cells (1.5 x 10(7)) were encapsulated and evenly suspended in a fibrin scaffold, and implanted to either side of the L5-L6 intertransverse space for six test rabbits. For the control group (six rabbits), the transfected cells (1.5 x 10(7)) were added on and absorbed in a surgical gelatin sponge, and implanted in an analogous location. Radiographs of the spine of all animals were taken at six, ten, and 12 weeks subsequent to fusion surgery. Gross and histological examination of the fusion masses for all the animals were performed subsequent to animals having been sacrificed at 12 weeks. RESULTS: Expression of BMP-2 was verified in the pCMV-BMP2 transfected NRK cells which were used for the subsequent rabbit experiment. For all 12 rabbits, no evidence of implanted-tissue rejection was seen during the postoperative course. Neither residual scaffold nor inflammatory granulation tissue was seen in the harvested spinal segments. For the six study-group rabbits, radiographic examinations revealed that four individuals (67%) featured prominent new-bone formation (good fusion), and two (33%) revealed moderate new-bone formation (fair fusion) at the implanted sites, whereas all six control-group rabbits revealed no evidence of new-bone formation (nonfusion) at the implanted sites. For the histological examinations, all animals in the study group revealed the presence of osseous tissue at the sites corresponding to the sites of radiographically demonstrated new-bone formation, whereas for the control group, no osseous tissue was seen at the implanted sites for any animal CONCLUSION: Fibrin gel, being a biocompatible and biodegradable matrix, can encapsulate pCMV-BMP2 transfected NRK cells and adhere to the intertransverse lumbar-spine spaces of test rabbits. With the above characteristics, it plays an important role in the successful delivery of pCMV-BMP2-transfected cells for this rabbit spinal-fusion experiment. Being a natural matrix and able to be obtained readily from patients' own blood, fibrin gel seems to be a promising scaffold for future gene therapy in human trials.

Animals↗
PubMed2005

Calpain inhibitor inhibits p35-p25-Cdk5 activation, decreases tau hyperphosphorylation, and improves neurological function after spinal cord hemisection in rats.

Aberrant calpain activation is a key mediator of neuron death. We examined the cell-permeable calpain inhibitor MDL28170 in the pathophysiological processes after spinal cord injury (SCI) including p35-p25- cyclin-dependent kinase-5 (Cdk5) activation, tau hyperphosphorylation, neuron cell death, calpain I activation, astrogliosis, and microglia activation. Our study showed that intrathecal administration of MDL28170 improved neurologic dysfunction, prevented neuron loss, decreased the number of apoptotic cells, and abated astrogliosis and microglia activation 7 days after spinal cord hemisection in rats. Reverse transcription polymerase chain reaction demonstrated calpain inhibition significantly attenuated the ratio of proapoptotic Bax/anti-apoptotic Bcl-2 mRNA in the lesion and penumbra after SCI. Calpain, the calcium-activated proteolytic enzyme, was found to digest p35 to its truncated product, p25. Moreover, abnormal Cdk5 activation by p25 and subsequent tau hyperphosphorylation triggers pathologic events leading to neurodegeneration and neurofibrillary tangles. We found p35-p25-Cdk5 activation and tau hyperphosphorylation in SCI, and then we showed that intrathecal MDL28170 treatment could diminish p35 truncation, and abrogate aberrant tau phosphorylation. Double labeling of calpain I and phosphorylated tau (AT8) in the same cells of spinal cord lesion further implicated pathogenesis of SCI. In conclusion, MDL28170 abated calpain I activation, inhibited apoptosis and neuron loss, quenched microglia and astrocyte activation, and significantly improved neurologic deficit one week after spinal cord hemisection. The neuroprotective mechanisms of calpain inhibitor in SCI could be attenuating upregulation of Bax/Bcl-2 ratio, preventing p35 truncation in the lesion and penumbra, and abrogating tau hyperphosphorylation.

Animals↗
PubMed2004

Altered serum transforming growth factor-beta1 and monocyte chemoattractant protein-1 levels in obstructive jaundice.

Impaired immune function has long been documented in patients with obstructive jaundice, and those with jaundice due to extrahepatic biliary obstruction still experience a high rate of postoperative complications and death. Transforming growth factor-beta1 (TGFbeta1) appears to be an important regulator of both normal and pathologic conditions in the liver. Monocyte chemoattractant protein-1 (MCP-1) is an important mediator of monocyte recruitment to inflammatory sites. We hypothesize that obstructive jaundice may alter serum TGFbeta1 and MCP-1 expressions in the rat and that oral bile acid or glutamine (or both) can restore the altered serum TGFbeta1 and MCP-1 expression in rats with obstructive jaundice. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (n = 10 in each group). Group 1 underwent a sham operation with oral normal saline administration. Group 2 underwent common bile duct ligation (CBDL) with oral normal saline administration. Group 3 underwent CBDL with oral bile acid replacement. Group 4 underwent CBDL with oral glutamine administration. Animals were sacrificed after 3 days (n = 5) and 7 days (n = 5), and blood samples were collected. Serum was obtained after centrifugation for measurement of TGFbeta1 and MCP-1 levels by an enzyme-linked immunosorbent assay. The serum TGFbeta1 level was significantly elevated (p = 0.006) 3 days after CBDL. Oral glutamine administration prevented this elevation, but oral bile acid replacement did not. The serum MCP-1 level showed similar changes. After 3 days of obstructive jaundice, the TGFbeta1 and MCP-1 levels were altered in the rat. Oral glutamine administration, not oral bile acid replacement, was able to prevent these alterations.

Animals↗
PubMed2004

Single injection of naked plasmid encoding alpha-melanocyte-stimulating hormone protects against thioacetamide-induced acute liver failure in mice.

Oxidative stress has been implicated in the propagation of acute liver injury. The aim of our study was to investigate whether gene transfer of alpha-melanocyte-stimulating hormone (alpha-MSH), a potent anti-inflammatory peptide, could prevent fulminant hepatic failure in mice. Acute liver damage was induced by intraperitoneal administration of thioacetamide. Hydrodynamics-based gene transfection with alpha-MSH expression plasmid via rapid tail vein injection was initiated 1 day prior to intoxication. The mortality in the alpha-MSH-treated mice was significantly lower compared to the vehicle group 3 days after injury. Liver histology significantly improved and TUNEL-positive hepatocytes decreased in the treated mice. The degradation of IkappaBalpha, endogenous inhibitor of nuclear factor kappaB, and upregulation of inducible nitric oxide synthase and tumor necrosis factor-alpha mRNA levels were prevented in the alpha-MSH-treated group, indicating decreased oxidative stress and inflammation. These results suggest alpha-MSH gene therapy might protect against acute hepatic necroinflammatory damage with further potential applications.

Animals↗
PubMed2004

Effect of glutamine and bile acid on hepatocyte apoptosis after bile duct ligation in the rat.

Apoptosis is an important process in a wide variety of biologic systems. Cholestasis, or impaired bile formation, occurs in a wide variety of human liver diseases. Retention and accumulation of toxic hydrophobic bile salts in hepatocytes may cause hepatocyte toxicity by inducing apoptosis. In addition, the translocation of bacteria and endotoxin, well documented in patients with obstructive jaundice, contribute to the induction of hepatocyte apoptosis. We hypothesized that oral bile acid replacement, glutamine administration, or both can attenuate or abolish hepatocyte apoptosis. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (10 in each group). Group 1 underwent a sham operation and was simultaneously treated with normal saline. Group 2 underwent common bile duct (CBD) ligation and was simultaneously treated with normal saline. Group 3 underwent CBD ligation and was simultaneously treated with oral glutamine. Group 4 underwent CBD ligation and was simultaneously treated with oral bile acid replacement. After 3 days (n = 5) and 7 days (n = 5), liver tissues were harvested for histopathologic analysis and apoptosis measurements. When compared with the sham operation group, significantly increased hepatocyte apoptosis and ductular proliferation occurred after CBD ligation for either 3 or 7 days. After administration of either glutamine or bile acid, the increased hepatocyte apoptosis and ductular proliferation after CBD ligation for 3 days were significantly diminished. However, both failed to diminish the changes after CBD ligation for 7 days. Significantly increased hepatocyte apoptosis and ductular proliferation occurred after CBD ligation. The administration of either glutamine or bile acid effectively diminished the hepatocyte apoptosis and ductular proliferation after CBD ligation for 3 days, whereas both failed to show the same effect after CBD ligation for 7 days.

Administration, Oral↗
PubMed2004

Single intravenous injection of naked plasmid DNA encoding erythropoietin provides neuroprotection in hypoxia-ischemia rats.

Hypoxic-ischemic (H-I) encephalopathy is a major contributor to morbidity and mortality in infants and children. To delineate the nature and mechanism(s) of neuroprotection via erythropoietin (EPO) gene therapy, we evaluated the effects of single intravenous injection of naked plasmid DNA encoding EPO in H-I infant rats. Single administration of naked plasmid containing EPO cDNA driven under cytomegalovirus promoter (pCMV-EPO) by rapid injection via the tail vein produced a remarkable level of human EPO protein in the circulation, peaking at one day and lasting for 14 days after injection. There were significant improvements of water maze task in H-I rats after EPO gene therapy. Our data showed that the mechanisms of EPO gene therapy were rescue of CA1 neurons from lethal H-I injury, prevention of neuronal apoptosis in CA1 region, and decrease of glial activation in corpus callosum. This could be the first report of successful treatment of H-I injury by a single intravenous infusion of EPO gene.

Animals↗
PubMed2004

Outcome after traumatic frontal intracerebral haemorrhage: a comparison of unilateral and bilateral haematomas.

Frontal intracerebral haemorrhage (ICH) is a common result of cranial trauma. Outcome differences between bilateral and unilateral frontal ICH are not well studied but would be valuable to predict prognosis in clinical practice. Two aims are proposed in this study: first to compare the risk of developing delayed ICH after bilateral or unilateral frontal ICH, and second to determine the variables helpful to predict outcome according to the Glasgow Outcome Scale (GOS). Between January 1993 and December 1997, 694 consecutive patients with traumatic ICH were admitted to the Chang Gung Medical Center within 24 h of the trauma. Patients with ICH in sites other than the frontal lobes were excluded. A total of 161 cases (mean age 46.3+/-20.3 years), including 57 bilateral (mean age 52.5+/-18.7 years) and 104 unilateral (mean age 42.9+/-20.5 years) traumatic frontal ICH were studied. Twenty-eight of 57 patients (49%) with bifrontal ICH versus 17 of 104 patients (16%) with unilateral frontal ICH had a further, delayed ICH. In 42 of 45 patients (93%) with delayed ICH, this occurred within 5 days of the initial trauma. Multivariate logistic regression was used to select significant predictors of outcome. We found that delayed ICH (p<0.001), age (p=0.004) and mechanism of injury (p=0.001) explained the worse outcome in patients with bifrontal ICH. The best-fitting logistic regression model included three variables: delayed ICH (p=0.011), initial GCS (p=0.023), and a sum score of clinical and radiological variables (p=0.003). Bifrontal ICH tended to occur in older patients after a fall and was associated with a higher risk of developing delayed ICH or brain stem compression compared to unilateral ICH damage. Using these three variables - delayed ICH, initial GCS, and the sum score - in a logistical regression model is useful to predict outcome in patients with traumatic frontal ICH and may aid patient management.

Adult↗
PubMed2004

Comparison of the handheld Retinomax K-Plus2 and on-table autokeratometers in children with and without cycloplegia.

PURPOSE: To compare the keratometry measurements in children by the handheld Nikon Retinomax K-Plus2 (Rmax) and the on-table Topcon KR8100 autokeratometers and evaluate the degree of agreement in the 2 instruments between children with and without cycloplegia. SETTING: Department of Ophthalmology, Kaohsiung Municipal United Hospital, and Chang-Gung Memorial Hospital, Kaohsiung, Taiwan. METHODS: The first cohort comprised 61 children who were consecutively collected in the pediatric ophthalmology clinic. The keratometry was measured under cycloplegia. The second cohort included 156 school children who received routine vision screening without cycloplegia. The horizontal and vertical keratometry data were measured by both instruments. The mean bias and agreement between the 2 types of measurements were evaluated. RESULTS: Both horizontal and vertical keratometry data from the Rmax were systemically and mildly lower than the data from the Topcon. The mean keratometric difference in the 2 types of instruments was minimal and clinically acceptable: 72% to 85% was within +/-0.5 diopter. The agreement of measured data in the children without cycloplegia was higher than that in the children with cycloplegia. CONCLUSIONS: The handheld Retinomax provided comparable data to that of the conventional on-table Topcon. It is useful in the clinic to measure keratometry in children and therefore may offer a convenient tool for assessing corneal curvature for fitting contact lenses or for implanting intraocular lenses in young children.

Child↗
PubMed2003

Comparison of measurements of refractive errors between the hand-held Retinomax and on-table autorefractors in cyclopleged and noncyclopleged children.

PURPOSE: To compare the measurement of refractive errors (sphere, cylinder, and axis) between the hand-held Retinomax and on-table Topcon autorefractors in cyclopleged and noncyclopleged young children. The average bias and measurement agreement were assessed. DESIGN: Observational cross-sectional study. METHODS: The study included 114 cyclopleged and 156 noncyclopleged young children. The mean difference between the two methods and the 95% limits of agreement were calculated to evaluate the average bias. Two types of analyses were conducted to assess the degree of agreement. First, the proportion of the absolute mean differences was presented in different ranges ( 1.0 diopters for sphere and cylinder; 0-10, 11-20 and >20 degrees for axis). Second, the paired t test was conducted to evaluate the consistency of two types of measurements. RESULTS: The data by the Retinomax had mild bias (0.59 diopters) toward a lower sphere data under noncycloplegia but no bias under cycloplegia. For cylinder and axis, there was either no bias or clinically acceptable bias (0.02-0.13 diopters for cylinder and 2-7 degrees for axis) regardless of cycloplegia. Besides the sphere data under noncycloplegia, in general 90% of the mean differences of sphere and cylinder were within 0.5 diopters. More than 97% of the difference in axis under cycloplegia and 68% under noncycloplegia were within 20 degrees. After adjusting for mild bias, the paired t test showed very consistent results. CONCLUSIONS: The data by the Retinomax were consistent with those by the Topcon. The Retinomax is a useful instrument to screen refractive errors in young children.

Child↗
PubMed2003

Prognostic significance of annexin VII expression in glioblastomas multiforme in humans.

OBJECT: Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor in adults. It is nearly uniformly fatal, with a median survival time of approximately 1 year, despite modem treatment modalities. Nevertheless, a range of survival times exists around this median. Efforts to understand why some patients live longer or shorter than the average may provide insight into the biology of these neoplasms. The annexin VII (ANX7) gene is located on the human chromosome 10q21, a site long hypothesized to harbor tumor suppressor genes associated with prostate and other cancers. To test whether ANX7 expression might be a predictor for GBMs, we examined ANX7 expression, p53 accumulation, and the MIB-1 labeling index in a retrospective series of 99 GBMs. METHODS: In all 99 cases, the patient's age, Karnofsky Performance Scale (KPS) score before surgery, extent of surgery, tumor location, and immunohistochemical features were analyzed using univariate and multivariate analyses to identify whether any significance exists among ANX7 expression, p53 accumulation, the MIB-1 labeling index, and survival time. Kaplan-Meier analyses demonstrated that a higher KPS score before surgery (< 0.0001), total tumor excision (p = 0.0072), young patient age (p = 0.03), and ANX7 expression (p = 0.0006) correlated with longer survival. Multivariate Cox regression analyses demonstrated that ANX7 expression was the strongest predictor of outcome (p < 0.0001), independent of all other variables. In addition, ANX7 expression correlated with higher MIB-1 immunostaining, but did not correlate with p53 accumulation. Moreover, a significant positive correlation was observed between p53 and MIB-1 staining. CONCLUSIONS: These findings indicate that a higher KPS score before surgery, total tumor excision, young patient age, and ANX7 expression correlate with longer survival in patients with GBMs. Multivariate Cox regression analyses demonstrated that ANX7 expression was the strongest predictor of outcome (p < 0.0001) and was independent of all other variables.

Adult↗
PubMed2002

Traumatic spinal subdural hematoma with spontaneous resolution.

STUDY DESIGN: A case report with a literature review is presented. OBJECTIVE: To describe and review the clinical presentations, characteristic findings from imaging studies, and treatment of traumatic spinal subdural hematoma. SUMMARY OF BACKGROUND DATA: Traumatic spinal subdural hematoma is uncommon, and only eight cases have been reported in the literature. Concomitant intracranial and spinal subdural hematoma in the same patient has not been well studied. METHODS: A case of concomitant spinal and intracranial subdural hematoma is reported as well as a review of the literature. RESULTS: Including our patient, we found that five of the nine patients with traumatic spinal subdural hematoma also had intracranial hematoma. We hypothesize that the mechanism of traumatic spinal subdural hematoma may be associated with intracranial events. Recognition of blood products in magnetic resonance imaging scans is important to distinguish spinal subdural hematoma from other spinal lesions. It is generally agreed that prompt laminectomy with evacuation of hematoma should be performed before irreversible damage to the spinal cord occurs. However, including our patient, three of the nine reported cases with thoracic or lumbar subdural hematoma resolved spontaneously with conservative treatment. CONCLUSIONS: This 12-year-old boy illustrated the rapid spontaneous resolution of traumatic subdural hematoma in both left hemisphere and lumbar spine with conservative treatment. This report suggests a possible role of conservative management for traumatic lumbar subdural hematoma, especially when the patients already have neurologic recovery.

Accidental Falls↗
PubMedDate not supplied

Protective effect of MDL28170 against thioacetamide-induced acute liver failure in mice.

Liver injury is known to often progress even after the hepatotoxicant is dissipated. The hydrolytic enzyme calpain, which is released from dying hepatocytes, destroys the surrounding cells and results in progression of injury. Therefore, control of calpain activation may be a suitable therapeutic intervention in cases of fulminant hepatic failure. This study evaluated the effects of a potent cell-permeable calpain inhibitor, MDL28170, and its mechanisms of action on thioacetamide (TAA)-induced hepatotoxicity in mice. We found that MDL28170 significantly decreased mortality and change in serum transaminase after TAA administration. The necroinflammatory response in the liver was also suppressed. Furthermore, a significant suppression of hepatocyte apoptosis could be found by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. The upregulation of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha), both of which are known to mediate the propagation of inflammation, was abolished. MDL2810 also effectively blocked hepatic stellate cell activation, which is assumed to be the early step in liver fibrosis. These results demonstrated that MDL28170 attenuated TAA-induced acute liver failure by inhibiting hepatocyte apoptosis, abrogating iNOS and TNF-alpha mRNA upregulation and blocking hepatic stellate cell activation.

Alanine Transaminase↗