Stabilization of mitochondrial function by Ginkgo biloba extract (EGb 761)

A large body of data emphasizes the central role of mitochondrial dysfunction during aging and as an early event in neurodegenerative diseases. In this study we used PC12 cells and dissociated mice brain cells, as well as isolated mitochondria to investigate the effects of EGb 761 on mitochondrial functions. We mimicked mitochondrial abnormalities during aging by using external factors (nitrosative stress, serum deprivation and complexes inhibitors) consequently altering mitochondrial processes, such as energy metabolism. As markers for the function of mitochondria, ATP levels and mitochondrial membrane potential were measured. EGb 761 alleviated mitochondrial functions in vitro at concentrations as low as 0.01 mg/ml. Treating two different age groups of mice with EGb 761 (100mg/kg body weight for 14 days) showed beneficial effects on complexes I, IV and V of the mitochondrial respiratory chain and against nitrosative stress. Interestingly, these effects were only observed in the aged mice group, proving higher efficacy of EGb 761 during aging. The single components of EGb 761 showed in both cell models protection of the mitochondrial membrane potential indicating that a complementary action of the components is responsible for the versatile actions of EGb 761.     

Modified sleeve anastomosis for reconstruction of the hepatic artery in rat liver transplantation

End-to-end sleeve anastomosis between a donor common hepatic artery and a recipient proper hepatic artery was proven to be the most physiological and simple method for hepatic rearterialization in rat liver transplantation. Current technical variants of the sleeve technique, however, are hampered by the high rate of bleeding from the anastomotic site. This report deals with a technical modification which inhibits postoperative bleeding efficiently. The procedure consisted of a guiding suture, as previously described in other technical variants, and a modified fixing suture. Instead of using a single stitch to fix the feeding vessel with the receiving vessel, a running suture between the edge of the donor common hepatic artery and the adventitia of the recipient proper hepatic artery was performed to avoid a possible backflow. The patency rate of 91% was as high as reported by others using a sleeve technique, which was also reflected in the histomorphological picture, being indistinguishable from normal liver histology. This technical modification simplified the procedure of reconstructing the hepatic artery and could contribute to a wider use of the arterialized liver transplantation model in rats.     

Influence of long term erythropoietin therapy on the hypothalamic-pituitary-thyroid axis in patients undergoing capd

OBJECTIVE: Treatment of anemia with recombinant human erythropoietin (rHuEpo) in hemodialysis patients has been associated with improvement of several abnormalities in hypothalamic-pituitary function. The aim of the present study is to investigate the effects of long term erythropoietin therapy on the hypothalamic-pituitary-thyroid hormone axis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Single center, prospective study. PATIENTS AND METHODS: Ten patients who were clinically stable and had been on CAPD were evaluated. Eleven age and sex matched healthy volunteers were chosen as controls. All of the patients were clinically euthyroid. All patients were on CAPD therapy and none of them had received rHuEpo treatment previously. In all patients after basal estimations of free T3, free T4, TSH, GH and prolactin levels, a bolus of 400 microg TRH was administered intravenously. Levels of TSH, GH and prolactin were measured in blood samples collected every 30 min of the 3 h test period. After the treatment with rHuEpo, TRH test with the same protocol was repeated. RESULTS: Before the improvement in serum hemoglobin levels with rHuEpo treatment, the patients on CAPD showed abnormal hypothalamic-pituitary-thyroidal functions, including delayed and prolonged TSH (NS), paradoxically elevated GH (p < 0.001) and increased and prolonged prolactin (p = 0.001) responses to TRH. After improvement of anemia with rHuEpo no significant difference was found between the patients and control groups for baseline TSH levels. In the patients peak TSH level and AUC of TSH secretion were significantly reduced after the treatment (p < 0.05 for both). Furthermore the improvement in anemia did not eliminate the paradoxic GH and prolonged prolactin responses to TRH administration. CONCLUSION: Some hypothalamic-pituitary-thyroid function abnormalities including delayed and blunted TSH, increased and prolonged prolactin and paradoxical GH responses to TRH administration were observed in uremic patients treated with CAPD and the improvement in anemia with rHuEpo seems to cause slight changes on the hypothalamic-pituitary-thyroid axis and peripheral thyroid hormones.     

Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis

Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)-matching influences the outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5-yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA-A, -B compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not influence the outcome. The occurrence of HBV-reinfection was significantly lower in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when compared with patients with HBV-reinfection and a complete HLA-B mismatch (p = 0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B compatibilities seems to be associated with an improved graft survival in patients after OLT for end-stage HBV infection.     

Treatment of severe lichen planus with mycophenolate mofetil

Lichen planus (LP) is an inflammatory skin disorder with a wide range of clinical appearances. The treatment of disseminated and especially erosive forms of LP is often difficult and disappointing. Activated T cells are important in the pathogenesis of LP as indicated by the dermal lymphocytic infiltrate leading to keratinocyte destruction and lesion formation. Similar histologic findings are present in graft-versus-host disease. Since T cells are key players in the development of both disorders and mycophenolate mofetil has been successfully introduced in the treatment of graft-versus-host disease, we have examined the therapeutic potential of this agent in 3 patients suffering from disseminated and erosive LP. Mycophenolate mofetil was well tolerated and induced complete remission in 2 patients, and substantial improvement in the third patient.     

Expanded newborn screening in Bavaria: tracking to achieve requested repeat testing

OBJECTIVES: Expansion of newborn screening programs may increase the risk of missing cases through procedural failures. A coordinated process quality assurance procedure to track recalls was, therefore, introduced in parallel to expansion (including MS-MS and 17alpha-OHP) in Bavaria. METHODS: Using comprehensive computerized registration and automated monitoring a state-funded center coordinated all individual measures to achieve complete testing of all repeat requests-case-specific contacts to physicians, midwives, and parents. Mailing and phoning from the center were supplemented by local public health activities including home visits if needed. RESULTS: Among 243,422 children tested in 1999 and 2000 overall recall was 3.62% (8,809 children): 0.30% (726) were due to sample inadequacy, 1.35% (3,282) to early sampling (<48 h), and 1.97% (4,801) to abnormal results. Of all recalls, 80.9% were received following the initial request, 1,679 (19.1%) required special efforts. Of these, 873 were achieved following a single and 601 following repeated central activities, and 102 were achieved following local support. Sixty-three cases of parental refusal and 47 untraceable children remained. Altogether, 98.8% recalls were achieved, corresponding to 99.96% of all tested children for which definite screening results could be obtained. CONCLUSIONS: Expansion of newborn screening programs does not necessarily mean unsolvable problems in tracking of recalls if adequate logistics is established in parallel.     

Very high compliance in an expanded MS-MS-based newborn screening program despite written parental consent

OBJECTIVES: In Bavaria, Germany, an expanded MS-MS-based newborn screening program was implemented in 1999. The coverage of new additional conditions and novelty of technology required introduction of written parental consent. Here we evaluated the influence of the consent procedure on compliance by systematic demographic tracking. METHODS: Comprehensive information was provided for parents, professionals, and the public. Screening notifications were matched with all birth notifications on name and date of birth. Parents of children without screening notification were contacted and counseled. RESULTS: Between August 1, 1999, and July 31, 2000, 123,284 children eligible for screening were born. Of these, 116,652 were matched successfully. Among 6,632 parents contacted, 2,516 (2%) did not respond. Three thousand thirty-four children were screened but the parents initially refused to participate in tracking. Five hundred ninety-four were screened outside the program. Four hundred eighty-eight untested newborns were identified. Three hundred twenty-five screening failures due to logistic problems were tested subsequently. Screening was definitely refused by the parents of 163 children (0.1% of target population). CONCLUSIONS: With appropriate information provided and surveillance by tracking, high compliance with newborn screening can be achieved despite a written consent requirement.     

Transfer of tissue factor from platelets to monocytes: role of platelet-derived microvesicles and CD62P

Tissue factor (TF) is the most important initiator of intravascular coagulation. Platelets contribute to TF exposure on monocytes, but the mechanism is not completely understood. Here we examined the possibility that platelets may release TF that can be transferred to monocytes by platelet-derived microvesicles. When human citrated platelet-rich plasma was incubated with collagen there was an increase in the plasma levels of TF and CD62P. Incubation of plasma obtained from collagen-stimulated PRP with a sediment of red and white blood cells resulted in an increase in the number of monocytes that express TF, CD62P and the platelet-specific antigen CD42a on their surface. This transfer of platelet-derived antigens to monocytes was reduced when CD62P was blocked by a specific antibody or when platelet-derived microvesicles were removed from the plasma either by high speed centrifugation (17,500 x g for 30 min) or by filtration (pore size 0.2 microm). The data indicate that platelet-derived microvesicles that are released from collagen-stimulated platelets may carry TF, CD62P and CD42a and may transfer these antigens to the surface of monocytes. The interaction of platelet-derived microvesicles with monocytes and the transfer of TF to monocytes strongly depend on CD62P.