Dendronpholides A-R, cembranoid diterpenes from the chinese soft coral Dendronephthya sp

A systematic examination of the Chinese soft coral Dendronephthya sp. resulted in the isolation and characterization of 18 new cembranoid diterpenes, namely, dendronpholides A-R (2-19), along with 11-episinulariolide and an enantiomer of sandensolide. Their structures were determined through extensive spectroscopic (IR, MS, 2D NMR) data analyses and by comparison with those reported in literature. The cytotoxicity of several compounds against human tumor cell lines was also evaluated.     

Residual factor VII activity and different hemorrhagic phenotypes in CRM(+) factor VII deficiencies (Gly331Ser and Gly283Ser)

Two cross-reacting material-positive (CRM(+)) factor VII (FVII) mutations, associated with similar reductions in coagulant activity (2.5%) but with mild to asymptomatic (Gly331Ser, c184 [in chymotrypsin numbering]) or severe (Gly283Ser, c140) hemorrhagic phenotypes, were investigated. The affected glycines belong to structurally conserved regions in the c184 through c193 and c140s activation domain loops, respectively. The natural mutants 331Ser-FVII and 283Ser-FVII were expressed, and in addition 331Ala-FVII and 283Ala-FVII were expressed because 3 functional serine-proteases bear alanine at these positions. The 331Ser-FVII, present in several asymptomatic subjects, showed detectable factor Xa generation activity in patient plasma (0.7% +/- 0.2%) and in reconstituted system with the recombinant molecules (2.7% +/- 1.1%). The reduced activity of recombinant 283Ala-FVII (7.2% +/- 2.2%) indicates that the full function of FVII requires glycine at this position, and the undetectable activity of 283Ser-FVII suggests that the oxydrile group of Ser283 participates in causing severe CRM(+) deficiency. Furthermore, in a plasma system with limiting thromboplastin concentration, 283Ser-FVII inhibited wild-type FVIIa activity in a dose-dependent manner.     

Monoclonal Antibody Specific for TIRC7 Induces Donor-specific Anergy and Prevents Rejection of Cardiac Allografts in Mice

T cell immune response c-DNA (TIRC7) is up-regulated during the early stages of T-cell activation in response to alloantigens. In this study, we analyzed the effects of newly developed monoclonal antibodies (mAb) against TIRC7 in acute cardiac allograft rejection. Fully vascularized heterotopic allogeneic heart transplantation was performed in mice across a full-mismatch barrier (C57Bl/10 into CBA). Recipients received seven injections (day 0-7) of a novel anti-TIRC7 mAb or remained untreated. Graft survival, histology and ex vivo lymphocyte functions were tested. Targeting of TIRC7 with an anti-TIRC7 mAb diminishes lymphocyte infiltration into grafts resulting in delay of morphological graft damage and prolongation of allograft survival. The lymphocytes from anti-TIRC7 mAb-treated animals exhibit hypo-responsiveness without evidence of lymphocyte depletion against the donor allo-antigens. Proliferation and expression of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) were down-regulated while interleukin-4 (IL-4) and IL-10 expression were spared. Moreover, anti-TIRC7 mAb enhanced up-regulation of CTLA-4 expression but suppressed up-regulation of CD25 on stimulated lymphocytes in vitro and in vivo. Ligation of TIRC7 has important effects on the regulation of co-stimulatory signaling pathways associated with suppressing of T-cell activation. Targeting of TIRC7 may therefore provide a novel therapeutic approach for modulating T cell immune responses during organ transplantation.     

The role of ultrasonography in the assessment of renal function in the elderly

BACKGROUND: Ageing is associated with a progressive loss of renal mass and kidney length and a decline in glomerular filtration rate (GFR). This study evaluated a possible correlation between renal function and kidney size measured by ultrasonography (US), and whether the latter helps estimate GFR in the elderly. METHODS: Twenty-five medically stable elderly patients (mean age 85 +/- 5 yrs) were examined in a geriatric ward at a university hospital. Blood samples were taken to determine serum creatinine (Cr) levels. On the same day, 51chromium ethylenediamine tetraacetic acid (51Cr-EDTA) clearance was performed as the gold standard of GFR. US measured kidney length, transverse and anteroposterior dimensions. RESULTS: Serum Cr (r=-0.67; p=0.0002), Cockcroft-Gault formula (r=0.82; p<0.0001), absolute length (r=0.51; p=0.008) and volume kidney (r=0.46; p=0.02) correlated significantly with GFR. After receiver operating curve (ROC) analysis, length was less specific than sensitive in detecting renal impairment. Adding length to the Cockcroft-Gault formula did not improve GFR estimation (p=0.44). In contrast, adding length to serum Cr levels improved GFR estimation (p=0.015). CONCLUSION: In the elderly, kidney length and volume significantly correlated with GFR. However, length has a low specificity in predicting renal impairment. Therefore, in clinical practice, serum Cr levels and calculated Cr clearance are more useful in predicting renal impairment. However, normal kidney length can help to exclude renal impairment in the elderly at risk of GFR underestimation by a calculated Cr clearance.     

Recurrence of functional mitral regurgitation in patients with dilated cardiomyopathy undergoing mitral valve repair: how to predict it

This study was aimed at identifying predictive variables for recurrence of mitral regurgitation (MR) in patients with dilated cardiomyopathy (DCM) undergoing mitral valve (MV) repair. From January 1997 to December 2005, 142 patients with DCM, 105 (73.9%) ischemic and 37 (26.1%) non-ischemic, underwent MV repair. Mean age was 66+/-10 years and mean MR grade was 3.2+/-0.7 (scale 1+ to 4+). Ninety-seven (71% ischemic, 29% non-ischemic), out of 98 still alive at follow-up, were included in this retrospective analysis. In all cases MV posterior annuloplasty was performed; all patients were followed-up by echocardiography (mean time interval of 44+/-28 months) to evaluate MR recurrence (>or=2+/4+). Thirty-day mortality was 9.2% (13 patients). Mean MR grade at follow-up was 0.9+/-0.9. Four-year freedom from MR recurrence was 65.5%+/-8.3. Cox analysis showed left ventricular end-diastolic volume index (LVEDVi, OR=1.03, P=0.016, AUC=0.72), left ventricular end-systolic volume index (LVESVi, OR=1.03, P=0.033, AUC=0.71), left ventricular ejection fraction (LVEF, OR=0.82, P=0.001, AUC=0.72), mitral valve coaptation depth (MVCD, OR=1.6, P=0.017, AUC=0.72) to be predictive variables for MR recurrence. Preoperative left ventricular dilatation and function along with degree of papillary muscle displacement can be helpful in identifying patients with higher probability to undergo a durable MV repair.     

Prevention of third molar development in dog with long pulse diode laser: a preliminary report

INTRODUCTION: Wisdom teeth continue to plague man with a high rate of frequency. It may be possible to prevent their development in children at an early age with a non- or minimally invasive technique, even before the tooth begins to form, by treating the soft tissue overlying the site of their development. A previous study that treated the intra-oral soft tissues of newborn rats with a 20 watt diode laser stopped third molar development up to 80% of the time with minimum observable side effects. This brief report describes a similar use of the diode laser in a limited number of young beagle pups. It is the first reported attempt at preventing third molar development in an animal model close in size to man. MATERIALS AND METHODS: Four 6-7 week old beagle pups were treated on one side of their mandibles with either a 20 or a 100 watt, 800 nm diode laser at a time third molar tooth buds are just beginning to form under the oral mucosa. Six months following treatment, the pups were examined intra-orally and radiographically for evidence of third molar formation. RESULTS: The two intra-oral sites that received the 20 watt diode laser treatment showed normal third molar development. The two intra-oral sites that received the 100 watt diode laser treatment did not develop third molars. CONCLUSIONS: The diode laser may be capable of selectively stopping third molar development and further studies are warranted.     

Primary hyperparathyroidism associated with hypocalcemia in a patient presenting with kidney disease

Elevated serum parathyroid hormone (PTH) level together with hypocalcemia in chronic kidney disease usually suggests secondary hyperparathyroidism. However, primary hyperparathyroidism should also be considered, especially if concomitant vitamin D deficiency is suspected. We report a case of parathyroid adenoma associated with hypocalcemia and metabolic bone disease in a patient presenting with kidney disorder. The patient was successfully treated by parathyroidectomy that was preceded and followed by intensive calcium and vitamin D supplementation.     

NEED FOR FACIAL REANIMATION AFTER OPERATIONS FOR VESTIBULAR SCHWANNOMA: PATIENTS PERSPECTIVE

A total of 779 patients operated on for vestibular schwannoma mostly by the translabyrinthine approach in Denmark during the period 1976-2000 answered a questionnaire about various postoperative consequences. In this paper we describe the patients' facial function evaluated by professionals one year postoperatively and self-evaluated by each patient according to the House-Brackmann scale at the time of the questionnaire. The patients' self-evaluation was more pessimistic than that of the professionals with 26% reporting House-Brackmann grade IV-VI, compared with 20%. One hundred and seventeen (15%) of 779 patients considered their facial palsy to be a big problem and 125 patients (16%) were interested in surgical treatment for the sequelae of facial palsy. Seventy-eight (10%) had already had some kind of operation, usually the VII-XII coaptation. Thirty-three of 61 patients who had already been operated on for facial palsy were interested in further surgical treatment. One hundred and ninety-five patients (25%) had some kind of operation on the eye, mostly (88%) a tarsorrhaphy. Reanimation procedures such as a palpebral gold weight or a spring, apparently still have a small place in Denmark. In conclusion, there seem to be a considerable and unmet need for surgical reanimation of facial function in patients with facial palsy after operations for vestibular schwannoma in Denmark.     

Basal Cell Carcinoma Treated with Interferon

Human natural leukocytic interferon (HNLI) and recombinant interferon (rIFN) alpha 2c can be used in the therapy of basal cell carcinoma. Seventy-two patients were treated for 3 to 6 weeks with a single dose of 400,000 to 1,200,000 units (HNLI) and 2,000,000 to 5,000,000 units (rIFN alpha 2c). According to histopathologic and clinical findings, 52 patients were cured, and cancer cells were not found in the biopsy material taken after HNLI treatment for the second biopsy. In nine of 72 patients the cancer lesion was reduced 25% to 90%. In 11 patients it was not reduced or was reduced less than 25%. With rIFN alpha 2c therapy given five times per week for 4 weeks, histopathologic and clinical findings showed that five patients out of 12 were cured, and cancer cells were not found in the biopsy material taken after treatment. In seven patients out of 12 the cancer lesion was reduced 25% to 90%. Both types of interferons are effective in the treatment of basal cell carcinoma. Side effects were mild.