Heart hypertrophy is a common finding of acromegaly, a syndrome due to GH excess. Impairment of adenine nucleotide translocase-1 (ANT-1) gene, the main mitochondrial ADP/ATP exchanger, leads to cardiac hypertrophy. The aim of the study was to evaluate cardiac expression and the functional role of ANT-1 in 1- to 12-month-old transgenic mice overexpressing bovine GH (acromegalic mice, Acro) and littermate controls (wild-type mice, Wt). GH specificity of protein degree variation was assessed treating Acro with pegvisomant, a GH receptor competitor. Tissue levels of ANT-1, NF-kappaB, ATP, and lactic acid were evaluated by western blot, bioluminescence, and Fourier transform infrared spectroscopy respectively. The degree of ANT-1 expression was higher in 1-month-old Acro than in Wt (47+/-5% OD vs 33+/-4% OD, P<0 01). On the contrary, ANT-1 expression was lower in 3- to 12-month-old Acro than in Wt (P<0 03). Changes in ANT-1 expression were associated with consistent changes of cellular ATP content, increasing at 1 month (P<0 05) and reducing thereafter in Acro when compared with Wt (P<0 04). Treatment with pegvisomant abolished ANT-1 and ATP changes observed in 1- and 3-month-old Acro, thus supporting a GH-dependent mechanism. Reduced ATP generation in hypertrophied hearts of older Acro was associated with increased lactic acid levels suggesting that part of energy was due to glycolysis. Variations in ANT-1 expression were linked to GH through changes in NF-kappaB, the levels of which changed accordingly. In conclusion, 1-month-old acromegalic mice had increased ANT-1 expression and higher degree of ATP production. Long-standing disease was associated with a consistent reduction of ANT-1 and ATP tissue levels, which became GH-independent in older animals. This study demonstrated a direct effect of GH on key proteins involved in energy metabolism of acromegalic hearts. 相似文献
The development and progression of a hepatocellular carcinoma (HCC) in a chronically diseased liver, i.e., the carcinogenesis,
comprise a multistep and long-term process. Morphologically, this process is associated with the presence of distinct nodular
lesions in the liver that are called ‘preneoplastic lesions.’ These preneoplastic lesions are associated with and can precede
the growth and progression of well-differentiated HCCs . The characterization of nodular lesions and demonstration of the
multistep development of HCC in the cirrhotic liver by imaging modalities represent a challenging issue. The arterial hypervascular
supply, depicted by different dynamic studies, represents a fundamental radiological criterion for the diagnosis of HCC in
cirrhosis. Magnetic resonance (MR) imaging performed with tissue-specific contrast media can help to investigate the “grey
area” of carcinogenesis, in which significant histological changes are already present without any imaging evidence of neoangiogenesis.
The purpose of this review is to provide information on the properties of tissue-specific MR contrast agents and on their
usefulness in the demonstration of the pathologic changes that take place at the level of the biliary and reticuloendothelial
systems during the carcinogenetic process in liver cirrhosis. 相似文献
Most ocular adnexal lymphomas (OAL) are extranodal marginal zone B-cell lymphomas (EMZL) of mucosa-associated lymphoid tissue (MALT)-type. Chronic antigen stimulation has been suggested to have a pathogenetic role in EMZL and Chlamydia psittaci chronic infection has been recently associated with the development of OAL in a series of patients from Italy. To assess this association, an evaluation of the presence of C. psittaci was made in a different OAL population. DNA samples were obtained from formalin-fixed, paraffin-embedded sections samples of 26 patients with OAL, 20 non-OAL and 20 benign ocular lesions, diagnosed and treated between 1998 and 2003 at National Institute of Oncology in Havana, Cuba. All samples were histologically reviewed by an expert pathologist. Fluorescence in situ hybrization (FISH) analysis of translocations involving MALT1 was performed. The presence of bacterial DNA was assessed with a multiplex touchdown enzyme time release polymerase chain reaction. DNA sequencing was performed to confirm suspicious bands. Seventy-three percent of the OAL cases were EMZL and 81% were in stage IE. FISH analysis was performed in 13 OAL cases and none of them evidenced MALT1 translocations. DNA of C. psittaci was detected in 11% of the 46 lymphomas: two orbital EMZL and three non-OAL. All 20 benign ocular lesions were negative for C. psittaci. The low prevalence of C. psittaci in OAL suggests geographical differences in the etiology of this entity. International studies are needed to clarify the role of C. psittaci in OALs. 相似文献
Conclusion: Our present findings demonstrate that resealing to cover the electrode is an effective method to treat vertigo after CI. An insufficient cochleostomy sealing can be regarded as a cause of postoperatively newly occuring vertigo after CI. A transtympanic revision is a promising treatment option in cases of post-operative dizziness.
Intoduction: A well-known and frequently reported complication after cochlear implantation is the appearance of postoperative vertigo symptoms. The aim of the present study was to observe if the postoperatively new occurrence of vertigo can be treated by resealing of the round window patch after cochlear implantation.
Material and methods: A retrospective analysis revealed that 10 patients underwent revision surgery transtympanally. Vertigo was assessed preoperatively and directly postoperatively and after 6 month after revision surgery by using the Dizziness Handycap Inventory (DHI).
Results: The most common symptom was rotating vertigo. A spontanous nystagmus was seen in four cases. No nystagmus was found after the revision surgery. In three cases, the onset of dizziness was associated with an event (sneezing, otitis media, climbing a mountain). A preoperative CT showed insuspectible results in seven patients but revealed pathologies two patients. Vertigo was improved significantly in six patients, and three of them were symptom-free. 相似文献
GH has antiapoptotic effects in cardiac or noncardiac cell lines; however, increased apoptosis has been found in myocardial samples of patients with acromegaly. The aim of this study was to investigate cardiac apoptosis and underlying molecular mechanisms in transgenic mice overexpressing bovine GH [acromegalic mice (Acro)] aged 3 or 9 months. Cardiomyocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase assay and annexin V; expression of pro- or antiapoptotic proteins was assessed by Western blot. Specificity of GH action was confirmed using a selective GH receptor antagonist. Apoptosis was lower in 3-month-old Acro than in controls; reduction was abolished by a GH receptor antagonist. The effects of GH were consistent with an antiapoptotic phenotype (increased Bcl2 and Bcl-XL and reduced Bad and cytochrome c levels, leading to lower activation of caspase-9 and caspase-3). In contrast, apoptosis was higher in 9-month-old Acro than in littermate controls; in addition, a GH receptor antagonist was without effect; the proapoptotic phenotype consisted in increased Bad, cytochrome c, caspase-9, and caspase-3. GH reduced apoptosis through p38 and p44/42 kinase pathways at young ages, whereas phosphatidylinositol-3-kinase was silent; on the contrary, the effects of GH on p38 and p44/42 kinase pathways were overcome by GH-independent stimuli in 9-month-old Acro. In addition, the antiapoptotic effect of GH was still present at this age as shown by phosphatidylinositol-3-kinase/Akt pathway activation. In conclusion, chronic GH excess reduced apoptosis at a young age, whereas its antiapoptotic action was overwhelmed in older animals by GH-independent mechanisms, leading to increased cell death. 相似文献