Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during resuscitation: effects of oxygen and carbon dioxide

BACKGROUND: Perinatal asphyxia is associated with cardiac dysfunction, and it is important to prevent further tissue injury during resuscitation. There is increasing evidence that myocardial matrix metalloproteinases (MMPs) are involved in myocardial hypoxaemia-reoxygenation injury. OBJECTIVE: To assess MMPs and antioxidant capacity in newborn pigs after global ischaemia and subsequent resuscitation with ambient air or 100% O(2) at different PaCO(2)-levels. METHODS: Newborn pigs (12-36 h of age) were resuscitated for 30 min by ventilation with 21% or 100% O(2) at different PaCO(2) levels after a hypoxic insult, and thereafter observed for 150 min. In myocardial tissue extracts, MMPs were analyzed by gelatin zymography and broad matrix-degrading capacity (total MMP). Total endogenous antioxidant capacity in myocardial tissue extracts was measured by the oxygen radical absorbance capacity (ORAC) assay. RESULTS: Matrix metalloproteinase-2 more than doubled from baseline values (P < 0.001), and was higher in piglets resuscitated with 100% O(2) than with ambient air (P = 0.012). The ORAC value was considerably decreased (P < 0.001). In piglets with elevated PaCO(2), total MMP-activity in the right ventricle was more increased than in the left ventricle (P = 0.008). In the left ventricle, total MMPactivity was higher in the piglets with low PaCO(2) than in the piglets with elevated PaCO(2) (P = 0.013). CONCLUSION: In hypoxaemia-reoxygenation injury the MMP-2 level was highly increased and was most elevated in the piglets resuscitated with 100% O(2). Antioxidant capacity was considerably decreased. Assessed by total MMP-activity, elevated PaCO(2) during resuscitation might protect the left ventricle, and probably increase right ventricle injury of the myocardium.     

Transarterial chemoembolization for HCC in patients with extensive liver transplantation waiting times

The treatment of hepatocellular cancer (HCC) with transarterial chemoembolization (TACE) prior to orthotopic liver transplant (OLT) is of increasing importance due to the rise in HCC incidence and donor shortage. This single-center study examines 28 patients treated with TACE and 7 patients not treated with TACE, with HCC prior to OLT between 1999 and 2008. The overall 1- and 5-year survival of all transplanted patients with HCC was 94% (33 of 35) and 80% (28 of 35). There was no difference in survival (P = .99) between patients who underwent transplantation immediately (median 95 days) and patients who had significantly longer wait times (median 308 days) when treated with TACE. During extensive wait times for OLT, TACE can be used to keep patients with HCC on the waiting list by preventing tumor progression, with similar outcomes compared with those who underwent transplantation immediately.     

Neovascularization after great saphenous vein ablation.

OBJECTIVE: To determine the prevalence, distribution, and flow characteristics of intraluminal neovascularization in patients undergoing great saphenous vein (GSV) endovenous laser (EVLT) or radiofrequency ablation (RFA). METHODS: Duplex ultrasound (DU) was performed in patients undergoing EVLT or RFA before, during, and after their procedures. Follow-up included assessment for deep venous thrombosis and obliteration. When new vessels were identified, the source, extent, direction, and location of flow were noted. Flow channel diameters were measured and the resistivity index (RI) was used to characterize the flow patterns. RESULTS: A total of 102 venous ablations were performed of which 46 were RFA, and 56 EVLT. Arterio-venous fistulae (AVF) were found in five patients that were not identified by DU prior to intervention. Involved segments had variable length and multiple channels (mean diameter 2.2mm). No patient had local or systemic symptoms related to the AVF. The mean RI was 0.42, consistent with an AVF. The perivenous arteries feeding the AVF had enhanced flow but a significantly higher RI (0.63, p<0.001). CONCLUSION: Multiple small vessels were found directly adjacent to the involved vein segments forming small AVF within the obliterated vein. The prevalence of AVF in the ablated GSV was 5%. This process may be responsible for recanalization or recurrence after endovenous ablation procedures.     

CCR4 expression in a case of cutaneous Richter's transformation of chronic lymphocytic leukemia (CLL) to diffuse large B-cell lymphoma (DLBCL) and in CLL patients with no skin manifestations

Objective: Richter’s transformation of B‐cell chronic lymphocytic leukemia (CLL) to cutaneous diffuse large B‐cell lymphoma (DLBCL) is very rare. We took the advantage of one of these cases to test the hypothesis that the chemokine receptor CCR4 is involved in the homing of CLL cells to skin. Patients and Methods: We evaluated CCR4 expression by flow cytometry in both circulating and skin CD19⁺ leukemic cells from a patient with cutaneous DLBCL. As controls, we used peripheral blood samples from CLL patients without skin manifestations and from elderly healthy donors. Results: We found that both DLBCL cells derived from the original CLL clone and circulating CLL cells from this patient expressed CCR4. Although it was previously reported that CCR4 is not expressed in CLL cells, we found that a low but significant proportion of leukemic cells from CLL patients with no skin manifestations do express CCR4. There was a positive correlation between the expression of CCR4 and the percentage of ZAP‐70 of each sample. Moreover, we consistently observed a higher expression of CCR4 within CD19⁺CD38⁺ and CD19⁺Ki67⁺ subsets compared to CD19⁺CD38^? and CD19⁺Ki67^? lymphocytes from the same sample, respectively. Conclusion: We conclude that the chemokine receptor CCR4 is not a special feature of CLL cells with skin manifestation, but rather it is expressed in a low but significant proportion of peripheral blood CLL cells.     

Defective NOTCH signaling drives increased vascular smooth muscle cell apoptosis and contractile differentiation in bicuspid aortic valve aortopathy: A review of the evidence and future directions

Bicuspid aortic valve (BAV) disease remains the most common congenital cardiac disease and is associated with an increased risk of potentially fatal aortopathy including aortic aneurysm and dissection. Mutations in the NOTCH1 gene are one of only a few genetic anomalies identified in BAV disease; however evidence for defective NOTCH signaling, and its involvement in the characteristic histological changes of VSMC apoptosis and differentiation in ascending aortae of BAV patients is lacking. This review scrutinizes the evidence for the interactions of NOTCH signaling, cellular differentiation and apoptosis in the context of aortic VSMCs and provides focus for future research efforts in the diagnosis of BAV aortopathy and prevention of catastrophic complications through NOTCH signaling manipulation.     

Damage and functional recovery of the Atlantic cod (Gadus morhua) inner ear hair cells following local injection of gentamicin

This study addresses the ultrastructural and functional damage and subsequent recovery of the inner ear in the Atlantic cod following intrasaccular gentamicin injection. Inner ear damage was assessed using SEM and measurements of AEP following 250-Hz pure-tone stimuli. Data from gentamicin-treated fish were compared with control (no injection) and sham (injection of saline) fish. Control fish had normal response thresholds associated with well-developed hair cell bundles in their macula sacculi. Sham fish had higher response thresholds compared with control fish during the first week post-intervention, but response thresholds were subsequently normal. Treated fish displayed significant inner ear damage associated with an increased average AEP threshold on the third day following treatment. Thereafter, inner ear tissue displayed signs of progressive regeneration until it was comparable to controls from the 14th day. Response thresholds were similar to those of control fish from the 17th day following treatment. These observations suggest that the macula sacculi of Atlantic cod can regenerate towards a near-complete functional and ultrastructural recovery within 17–21 days following ototoxic gentamicin treatment.