[USF1 Suppresses Expression of Fibrillar Type I, II, and III Collagen and pNP Adamts-3 in Osteosarcoma Cells].

Collagens are the main components of human tissues. Various regulatory factors and cytokines may influence expression levels for collagen-encoding genes, and, therefore, contrubite to some collagen-associated pathologies. In this study, we demonstrate regulatory effects of USF1 on expression of genes encoding fibrillar collagen types I, II, and III in osteoblastic Saos-2 and MG-63 cells. An ectopic expression of the human USF1 led to a decrease in both mRNA and protein expression levels of the collagen-encoding genes mentioned above. ADAMTS-3 is a proteinase primarily responsible for the amino-terminal cleavage of type I and type II collagen precursors. The ADAMTS-3 promoter region contains potential binding sites for USF1. Here we show that an overexpression of USF1 lead to a decrease in ADAMTS-3 mRNA and protein expression levels. In co-transfection studies, USF1 negatively regulated ADAMTS-3 promoter activity. Further, in EMSA studies, we showed that USF1 binds to the ADAMTS-3 promoter region. In conclusion, it seems that ADAMTS-3 and USF1 contribute to the regulation of collagen encoding genes in osteosarcoma.

Recombinant adiponectin inhibits inflammation processes via NF-kB pathway in acute pancreatitis.

PURPOSE:   Adiponectin is a protein stemming from adipose tissue and having strong anti-inflammatory properties. We aimed to assess the damage diminishing effects of recombinant adiponectin  (rAD) through NF-kB in the experimental acute pancreatitis  (AP) model. MATERIALS AND METHODS:   Acute pancreatitis was created by applying 50 µg/kg dose of intraperitoneal cerulean. The rats were randomised and divided into 3 groups as control, AP and rAD groups. Moreover, the rats in each group were divided into two sub-groups as 24th and 48th hour subgroups. rAD was injected in the study group intraperitoneally. Tissue and blood samples were taken after 24 and 48 hours. Histopathological assessment and NF-kB activity were investigated in pancreatic tissue. RESULTS:   Serum TNF-a, IL-1b and IL-6 levels were found to be statistically significant in the AP group compared to the rAD group in the 24th and 48th hour  (p < 0.05). Similarly, NF-kB activity was also found to be significant in the AP group both in the 24th and 48th hour  (p < 0.05). There were significant differences in the AP and the rAD groups histopathologically in terms of edema, inflammation, vacuolisation and necrosis  (p < 0.001). CONCLUSION:   rAD has significantly reduced NF-kB activity, cytokine levels and tissue damage  (Tab. 1, Fig. 1, Ref. 51).

Toxic Adenoma in a Patient with Thyroid Hemiagenesis.

Thyroid hemiagenesis (TH) is a rare congenital anomaly that is usually asymptomatic. Functional disorders of the thyroid make the patient symptomatic. TH is usually and incidentally established during evaluation of patients with symptomatic thyroid pathology. We report the case of a patient of TH who became symptomatic with hyperactivity of the gland. The patient presented with signs and symptoms of thyrotoxicosis. Physical examination revealed asymmetric nodular goiter at the right lobe. Biochemical analysis established the diagnosis of hyperthyroidism. Ultrasound of the thyroid gland revealed the absence of the left lobe and a large, solitary hypoechoic solid nodule in the right lobe. Nuclear scan showed the absence of the left lobe and revealed a large, autonomous solitary nodule in the right lobe. The diagnosis was a toxic adenoma. After medical control of hyperthyroidism, the patient was surgically treated with hemithyroidectomy. We prescribed postoperative replacement medication with L-thyroxin. Hyperthyroidism makes TH cases symptomatic. Thyroid ultrasound and scintigraphy incidentally discover agenesis of one lobe during evaluation of thyrotoxicosis. Hemithyroidectomy, including the autonomous nodule, is the procedure of choice for patients with toxic adenoma. Hemithyroidectomy in TH cases technically becomes a total thyroidectomy with a need for postoperative thyroid replacement therapy.

Evaluation of health-related physical fitness parameters and association analysis with depression, anxiety, and quality of life in patients with fibromyalgia.

AIM: The purpose of this study was to investigate the physical fitness parameters (maximal aerobic capacity, muscle strength and flexibility), daily physical activity, resting metabolic rate (RMR), pulmonary function tests (PFTs), body composition, depression, anxiety and health-related quality of life (HRQoL) changes as well as the associations among these parameters in patients with fibromyalgia and to compare them with healthy controls. METHODS: Thirty-nine women with fibromyalgia and 40 controls were included in this study. Physical measurements, HRQoL questionnaire, Beck Depression Inventory (BDI) score and Beck Anxiety Inventory (BAI) score were applied to all participants. RESULTS: Maximal aerobic capacity, trunk flexibility, daily step numbers, total energy expenditure, RMR and PFT values were not significantly different between the patients and the controls. Fibromyalgia patients had higher daily moderate activity times, active energy expenditure values, and BDI and BAI scores, while their lower handgrip strength and back-leg strength values and Short-form health survey (SF)-36 scores were comparable to controls. Handgrip strength and back-leg strength values showed moderately positive correlations with SF-36 scores (total, physical health, mental health) and moderately negative correlations with BDI and BAI scores in patients with fibromyalgia. CONCLUSION: Our results suggested that muscle strength, HRQoL, depression and anxiety symptomatology were impaired in fibromyalgia patients compared to healthy controls. Low muscle strength is related to reduced HRQoL and increased depression and anxiety symptomatology in patients with fibromyalgia. Also we suggest that performing daily exercises, including aerobic and strength training, as part of one's lifestyle may have beneficial effects in fibromyalgia patients.

Reduction of Inflammation Drives Lipid Changes in Ankylosing Spondylitis.

OBJECTIVE: To investigate the effects of changing inflammation on lipid levels in ankylosing spondylitis. METHODS: In a cohort of 230 patients, lipid levels were measured at baseline and after 52 weeks of treatment with tumor necrosis factor-α-blocking agents (anti-TNF). RESULTS: Total cholesterol (TC; +4.6%), low-density lipoprotein cholesterol (+4.3%), and high-density lipoprotein cholesterol (HDL-C; +3.7%) increased upon treatment. Changes were most evident in patients with substantial reduction in inflammatory levels (TC +8.2% vs +1.6% and HDL-C +8.3% vs +2.2% in patients with C-reactive protein ≥ 10 mg/l normalizing upon treatment vs CRP < 10 mg/l throughout treatment period). CONCLUSION: Anti-TNF therapy results in lipid changes mostly when inflammation is appreciably modified.

Cardiovascular risk management in patients with active ankylosing spondylitis: a detailed evaluation.

BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory disease with documented elevated cardiovascular (CV) risk due to systemic inflammation and a higher prevalence of CV risk factors. CV risk management (CV-RM) could be an effective method to reduce CV mortality and morbidity in AS patients. We assessed CV risk and evaluated guideline adherence according to the Dutch CV-RM guideline. METHODS: This study was conducted with a cohort of consecutive AS patients eligible for treatment with a tumor necrosis factor (TNF) -α inhibitor. Data from the Dutch National Institute for Public Health and Environment was used to compare the prevalence of CV risk factors in AS patients with the Dutch background population. RESULTS: In total, 254 consecutive AS patients were included. The prevalences of hypertension (41% vs 31%) and smoking (43% vs 27%) were substantially higher in AS patients as compared to the general Dutch background population. Of 138 AS patients older than 40 years the 10-years CV risk could be calculated. Fifty-one of these 138 patients (37%) had an indication for CV risk treatment. CV risk treatment was initiated in 42 of the 51 (82%), however, in only 12 of the 51 (24%) patients treatment targets for either hypertension or hypercholesterolemia were reached. CONCLUSION: The increased rates of hypertension and smoking illustrate the importance of CV-RM in AS patients. Although the majority of all AS patients eligible for CV-RM received CV risk medication, CV-RM remains a challenge for treating physicians, as treatment targets were not achieved in three-quarter of the eligible patients.

Tumour necrosis factor blocking agents and progression of subclinical atherosclerosis in patients with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is associated with an increased cardiovascular risk that might be due to the chronic underlying inflammatory process. We investigated whether subclinical atherosclerosis of the carotid artery in patients with AS was reduced after anti-inflammatory treatment with tumour necrosis factor (TNF) inhibitors in a prospective observational cohort study. METHODS: 67 out of 81 AS patients who used TNF inhibitors and underwent ultrasonography at baseline returned for follow-up after 4.9 years. Of all patients, 12 (15%) discontinued the use of TNF inhibitors. Assessments of medication use, AS-related factors and cardiovascular risk factors were measured at baseline and repeated at follow-up. B-mode carotid ultrasonography was used to investigate arterial wall parameters, including carotid intima-media thickness (cIMT) and Young's elastic modulus (YEM). RESULTS: After a median 4.9 years of follow-up, cIMT did not change significantly (paired t test +0.011 mm, p=0.561) in those who continued the use of TNF inhibitors, while cIMT increased substantially (+0.057 mm, p=0.069) in those who did not continue their use of TNF inhibitors. The effect of TNF inhibitors was mainly mediated by a subsequent decrease in AS disease activity. Vascular elasticity (as measured with YEM) did not change significantly in patients who discontinued TNF inhibitors or those who continued TNF inhibitors. CONCLUSIONS: The use of TNF inhibitors might stabilise or slow down the progression of subclinical atherosclerosis in AS patients, reflecting a decreased cardiovascular risk in these patients.

Results of surgery-related complications in donors of right lobe liver graft: analysis of 272 cases.

BACKGROUND: Living donor liver transplantation has been a new light of hope for patients with end-stage liver failure on the cadaveric waiting list. However, living donor liver transplantation still has ethical problems which cannot be overcome. Exposure of healthy donor candidates to major surgery which can be fatal is the largest of these ethical problems. In this study, we aimed to determine our rate of complications associated with surgery in donors who underwent right lobe donor hepatectomy. MATERIALS AND METHODS: Between September 2004 and December 2009, 548 liver donor candidates were examined. The right liver lobe donor hepatectomy was performed on 272 donor candidates who passed the elimination system. Demographic data as well as intraoperative findings, complication rates, and numbers were collected retrospectively. Donor complications were categorized according to the Clavien classification. RESULTS: Two hundred seventy-two donors who underwent right lobe donor hepatectomy were included in this study. One hundred sixteen (42.6%) of 272 donors were female, whereas 156 (57.4%) were male. There was no donor mortality. Grade 1 and grade 2 complications were observed in 105 (38%) of 272 donors. The most common complications were fever of unknown origin (20.9%) and prolonged hyperbilirubinemia (3.6%). Grade 3 complications and grade 4 complications were observed in 6 donors (2%) and 3 donors (1%), respectively. Three donors were underwent re-operation due to bleeding. The re-laparatomy rate in our series was detected as 1.10%. One donor, categorized as grade 4B according to the Clavien classification, had small bowel perforation and intra-abdominal sepsis secondary to mechanical bowel obstruction. CONCLUSIONS: Donor mortality is a fact of living donor liver transplantation that cannot be ignored like donor morbidity. However, right liver lobe donor hepatectomy can be performed successfully with minimal complication rates with multidisciplinary and rigorous donor care in the preoperative and postoperative period.

Myocardial infarction after rituximab treatment for rheumatoid arthritis: Is there a link?

Rituximab is an anti-CD20 monoclonal antibody often used in the treatment of rheumatoid arthritis (RA). Infusion reactions sometimes develop following rituximab administration. Delayed complications are rare. Acute coronary syndromes are listed as sideeffects of rituximab therapy. We report two cases of acute myocardial infarction following rituximab therapy for RA and review the literature regarding cardiac events in patients treated with rituximab. We would like to raise awareness of this possible complication in patients treated with rituximab.

The angiogenic effects of ischemic conditioning in experimental critical limb ischemia.

OBJECTIVES: Ischemic conditioning (IC) is a method of angiogenic stimulus for limb ischemia. Here, we aimed to investigate the effects of short-term repeated ischemic stimulus on critical lower limb ischemic injury. METHODS: Rats were divided into four groups consisting of 40 animals in each group: sham, ischemia, local IC, and remote IC groups. Right-leg critical limb ischemia was achieved through ligation of the iliac artery and vein in male Sprague-Dawley rats except the sham group. Repeated transient ischemia using the tourniquet method was used for IC of lower extremities in the local and remote groups. IC was performed on the right leg for the local group and on the left leg for the remote group. Ten rats in each group were sacrificed for evaluation on days 1, 7, 14, and 30. Endothelial progenitor cell (EPC) counts were measured. Gastrocnemius muscles were evaluated for the degree of ischemia. Laser Doppler blood flow measurements were performed in order to make comparison between the blood flows of the limbs of the groups. RESULTS: The blood flow in the right limb of rats in the sham (1.65 perfusion units [PU]) and local IC (1.67 PU) groups was significantly higher than the ischemic group (1.17 PU) (p = .001 and p = .022 respectively). The levels of EPCs in the ischemia (1.09 ± 0.5) and remote IC groups (1.36 ± 0.8) were significantly higher than the sham (0.38 ± 0.2) group on day 7 (p = .026 and p = .002 respectively). Remote IC and local IC groups exhibited increased histopathological ischemia on day 7 when compared with sham group (p = .001, p = .01 respectively). The angiogenic scores on the 7th, 14th and 30th days for local IC and remote IC groups were significantly higher than sham and ischemia groups. CONCLUSIONS: IC seems to be the potent activator of angiogenesis in ischemic tissue. This study provides preliminary data showing that repeated short ischemic stimuli may reduce critical ischemic injury by promoting angiogenesis.

Management of cardiovascular risk in patients with rheumatoid arthritis: evidence and expert opinion.

The risk of cardiovascular morbidity and mortality is increased in rheumatoid arthritis. The classical cardiovascular risk factors, including smoking, hypertension, dyslipidaemia, insulin resistance and diabetes mellitus, obesity and physical inactivity do not appear to explain the excess cardiovascular risk in rheumatoid arthritis, although they do contribute, albeit in a different way or to a lesser extent, to rheumatoid arthritis in comparison with the general population. A very important link between rheumatoid arthritis and cardiovascular disease is inflammation as it plays a key role in all stages of atherosclerosis: from endothelial dysfunction to plaque rupture and thrombosis. It also has an influence on and accentuates some traditional cardiovascular risk factors, such as dyslipidaemia, obesity and insulin resistance. To date, the exact pathophysiologic mechanism by which this relation between cardiovascular disease and rheumatoid arthritis can be explained is not completely clear. Cardiovascular risk management in rheumatoid arthritis is mandatory. Unfortunately, the way this should be done remains a point of discussion. In this review issues regarding cardiovascular risk in rheumatoid arthritis and its management will be addressed, according to evidence presented in the latest studies and our own experience-based opinion.

The effects of tumor necrosis factor inhibitors on cardiovascular risk in rheumatoid arthritis.

There is abundant evidence that rheumatoid arthritis (RA), a chronic inflammatory disorder, is associated with an increased risk for cardiovascular (CV) disease. While there may be several mechanisms contributing to a higher CV risk in RA patients, inflammation is considered to be the main cause explaining the excess CV burden. Inflammatory processes appear pivotal to the atherothrombotic process and are linked to endothelial dysfunction, fatty streak initiation and progression, deterioration of fatty streaks into (unstable) plaques, and plaque rupture. Moreover, systemic inflammation, through tumor necrosis factor (TNF) or related cytokines, appears to accelerate atherothrombosis either directly or via effects on conventional and novel CV risk factors, such as lipids and lipoproteins, blood pressure, haemostatic factors, and insulin resistance. New and highly specific therapeutic agents (TNF inhibitors) may significantly lower CV risk in RA. This review summarizes the evidence base supporting the notion that TNF inhibitors confer benefit CV disease risk in RA.

The effect of TNF-alpha blocking therapy on lipid levels in rheumatoid arthritis: a meta-analysis.

OBJECTIVES: Changes in the lipid profile have been described in patients with rheumatoid arthritis (RA) following therapy with tumor necrosis factor (TNF)-alpha blocking agents. However, thus far, results have been inconsistent. Therefore, we investigated changes in lipid levels after TNF-alpha blocking therapy using meta-analysis of published data. METHODS: The literature was searched to identify studies assessing changes in total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol, triglycerides, atherogenic index (ie, TC/HDLc ratio), and apolipoprotein levels in response to TNF-alpha blocking therapy. Weighted mean levels of lipids at different time points and subsequent changes in these lipid levels between these time points were calculated with multivariate linear mixed models. RESULTS: Data were available on TC in 15 studies encompassing 766 RA patients and on HDLc in 14 studies encompassing 736 RA patients. TC increased significantly (maximum increase of 10%) and HDLc increased significantly in the first 2 to 6 weeks of therapy (maximum increase of 7%), after which it remained more or less stable. The atherogenic index did not significantly change over time. There was too limited information to evaluate changes in other lipids and apolipoproteins. CONCLUSIONS: TNF-alpha blocking therapy has a modest effect on TC and HDLc levels in RA patients with no significant overall effect on the atherogenic index. Whether TNF-alpha blocking effects on qualitative lipid changes (structure and function) are more relevant to their presumed vascular benefits requires further study.

Pathologic assessment of non-palpable probably benign breast masses at sonography: can instant intervention be avoided and is follow-up adequate?

AIM OF THE STUDY: To evaluate the pathologic results, determine the negative predictive value of non-palpable probably benign lesions at ultrasound and asses whether follow-up is adequate and immediate biopsy can be avoided. MATERIALS AND METHODS: Four hundred and eight cases which were referred to our breast imaging unit between 2004 and 2008 for biopsy evaluation were enrolled into the study. Two hundred and thirteen probably benign solid masses are classified as BI-RADS 3 in 205 of the enrollees. All masses were sonographically detectable and were classified through the guidelines of BI-RADS lexicon for sonography before the final pathological examination. All pathologic results were evaluated and the negative predictive value, false negativity rate and 95% confidence interval were calculated. RESULTS: Of the 213 masses, fine needle aspiration cytology was performed in 120. US-guided wire localization and eventual surgery were carried out in the remaining 93 masses. Finally, 211 of the punctured lesions turned out to be benign and only two malignant lesions were detected. The resulting negative predictive value was found to be 99.1% while the false negative rate value was 0.9%. CONCLUSION: With the results provided, we think that in the patients with sonographically detected probably benign breast lesions, short-term follow-up seems to be a strong alternative to immediate biopsy with its reliable high negative predictivity as well as low false negativity.

Epidural extension of a lumbar vertebral haemangioma.

Vertebral haemangiomas are relatively common, but those extending into the epidural space are rare. A 59-year-old man with severe lower back and right leg pain that did not resolve with conservative treatment was seen in an outpatient clinic. Magnetic resonance imaging of the lumbar spine identified an L3 vertebral corpus lesion with epidural extension. The diagnosis was unclear, so the patient underwent surgery. The pathologic diagnosis was capillary haemangioma, so angiography-guided embolization was performed postoperatively. Vertebral haemangioma must be considered when there is evidence of a vertebral corpus lesion with epidural extension on magnetic resonance imaging.

Can sarcoidosis cause autoamputation of a finger phalanx?

Sarcoidosis is a multisystemic granulomatous disease. In the case presented, autoamputation of the distal phalanx of a little finger of the left hand was observed. The possibility of autodigital amputation as a result of sarcoidosis is discussed.