Heart valve calcification and calcium x phosphorus product in hemodialysis patients: analysis of optimum values for its prevention

BACKGROUND: Prevalence of valve calcification (VC) in end-stage renal disease (ESRD) patients is high and information regarding modifiable predictors is scarce. Our aim was to determine the prevalence of VC in our maintenance hemodialysis (HD) population, and the optimal Ca x P value that most accurately predicted the presence of VC after controlling for comorbidities. METHODS: This was a cross-sectional observational study of a cohort of 52 stable patients on maintenance HD for more than 12 months. Mean 12 months serum biochemical data (calcium, phosphorus, PTH, lipids) and M-mode 2D echocardiogram were used to evaluate the presence or absence of mitral and aortic VC and ventricular geometry. RESULTS: Twenty patients (38.4%) presented with VC. Patients with VC were more commonly diabetic and showed higher levels of serum phosphorus, Ca x P product, total and LDL cholesterol, and poor ventricular geometry, as compared to patients without VC. Moreover, they required higher doses of both CaCO3 and Al(OH)3. Logistic regression analysis showed that VC was independently influenced by age, Ca x P, and diabetes. ROC curves illustrated that a Ca x P>43 mg2/dL2 was the optimal value in terms of sensitivity and specificity for predicting the presence of VC in our patient population. CONCLUSION: These findings highlight the importance of applying more vigorous measures for Ca x P control.     

IS20I,a specific alphavbeta3 integrin inhibitor,reduces glioma growth in vivo

OBJECTIVE: The biological features of malignant gliomas include high cell proliferation, extensive local infiltration of tumor cells into normal brain, and marked neovascularization. alphavbeta3 integrin is highly expressed in malignant gliomas and plays a role in glioma growth. This article investigates the in vitro and in vivo effects of a synthetic alphavbeta3 integrin inhibitor called IS20I on human malignant gliomas. METHODS: The in vitro effects of IS20I were studied by performing adhesion assays, competition studies, semi-in vivo angiogenic assays, and migration and proliferation assays. For the in vivo experiments, IS20I was administered systemically in nude mouse intracranial and subcutaneous malignant glioma models. RESULTS: IS20I reacted selectively to alphavbeta3 integrin in glioma cells and tissues. In vitro, IS20I strongly inhibited angiogenesis and simultaneously exhibited potent antimitotic and antimigratory effects on numerous tumor and endothelial cell lines. In addition, at high concentrations, IS20I induced endothelial and tumor cell apoptosis. In vivo, when IS20I was administered intraperitoneally in subcutaneous and intracranial nude mouse glioma models, it potently reduced malignant glioma growth. Inhibition levels of 76 and 82% were observed at concentrations of 1 and 5 mg/kg, respectively, in the U87 intracranial model. The suppression of tumor growth is associated with a decrease in tumor vascularity, an increase in apoptosis, and a decrease in tumor cell proliferation. CONCLUSION: This work expands the understanding of the effects of anti-alphavbeta3 integrin inhibitors on malignant gliomas. In addition to direct proapoptotic and antiangiogenic effects, IS20I inhibits tumor and endothelial cell proliferation and migration, resulting in a potent inhibition of glioma growth in vivo.     

Smoking may impair the bone protective effects of nutritional calcium: a population-based approach

Postmenopausal women were randomly selected to investigate the effects of smoking on prevention of bone loss with nutritional calcium. DXA was performed twice, and smoking and calcium intake habits were inquired through the mail in 954 women. Smoking dampened the bone protective effects of nutritional calcium. This may reflect the pathophysiology underlying smoking-induced bone loss postmenopause. This study evaluated the effect of smoking on the bone protective properties of nutritional calcium. Of the random sample of 954 peri- and postmenopausal women selected from the Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort (n = 13,100) in Kuopio, Finland, 182 had smoked at some time (ever smokers) and 772 had never smoked. Women were divided in tertiles according to self-reported dairy nutritional calcium intake (mg/day): < 648 (1st), 648-927 (2nd), > 927 (3rd). Bone mineral density at lumbar spine (LS) and femoral neck (FN) was measured with DXA at baseline in 1989-1991 and at the 5-year follow-up in 1994-1997. In a linear regression model, nutritional calcium intake did not predict annual bone loss in smokers. These results were similar in the subanalysis on 71 current smokers (at both baseline and 5-year measurements) and on 85 past smokers. In never smokers, a statistically significant linear trend was observed between calcium intake and annual bone loss at LS, but at FN only after adjustment for age, weight, hormone replacement therapy (HRT), and other covariates. In analysis of covariance (ANCOVA), no differences in bone loss rate were observed between calcium intake tertiles among smokers. In nonsmokers, the annual bone loss rate was lower in the second (-0.41%) and the third (-0.35%) tertile compared with the first tertile (-0.61%) at LS (p < 0.05) and lower in the third tertile (-0.55%) than in first tertile (-0.72%) at FN after adjustment for age, weight, HRT, and other covariates (p < 0.05). When smokers were added to the nonsmoker group, the differences in bone loss rate between calcium intake tertiles disappeared. In addition, in ANCOVA, the term of interaction between smoking and calcium intake was statistically significant at LS only. In conclusion, smoking seems to impair the bone protective effects of nutritional calcium in postmenopausal women, more clearly in LS than FN.     

Contact versus peribulbar anaesthesia in trabeculectomy: a prospective randomized clinical study

PURPOSE: To compare the pre-, intra- and postoperative pain scores and complication rates in trabeculectomy under contact-topical anaesthesia versus peribulbar injection anaesthesia. METHODS: A total of 100 patients selected to undergo primary trabeculectomy were randomly allocated to receive either contact or peribulbar anaesthesia. Patients were asked to rate their pain levels on a 5-point scale for four periods: during the administration of the anaesthetic agent, during surgery, immediately after surgery and 24 hours postoperatively. At the same time, the surgeon was asked to record his subjective assessment of the stress he himself had suffered during the course of the intervention. Surgical parameters, intra- and early postoperative complications were also evaluated. RESULTS: The difference between groups was statistically significant during anaesthetic administration. Six patients who received contact-topical anaesthesia reported mild discomfort during delivery of the anaesthetic agent, while 43 patients complained of mild to severe pain during the injection of bupivacaine (p < 0.001). Thirty-two patients in the contact anaesthesia group and 26 in the injected anaesthesia group reported no pain during surgery (p = 0.127). Only one patient in each group reported mild pain 30 min postoperatively. We found no differences between pain rates after surgery. Complications included prolonged chemosis and we also noted that conjunctival haemorrhage occurred more frequently in the peribulbar group than in the contact anaesthesia group (p = 0.012). CONCLUSION: Both anaesthetic methods provided high levels of pain control without additional sedation during surgery. The use of contact-topical anaesthesia reduces both pain and the possibility of complications during the administration of anaesthetics.     

Characterisation of the anticholinesterase activity of two new tacrine-huperzine A hybrids

The effects of two tacrine-huperzine A hybrids, (+/-)-huprine Y and (+/-)-huprine Z, have been evaluated. Bovine and human acetylcholinesterase (AChE) and human butyrylcholinesterase (BChE) inhibition were assayed by Ellman's method. The two huprines were more active than both tacrine and (-)-huperzine A as inhibitors of both human and bovine AChE, and they acted as mixed-type AChE inhibitors. Moreover, (+/-)-huprine Y exhibited a tight binding character seen in the experiments of reversibility of bovine AChE inhibitory activity. In addition, both compounds were more active toward AChE than toward BChE. Also, the selectivity for the human AChE was greater than for the bovine enzyme. In ex vivo studies performed in mice, both drugs showed a clear inhibitory activity of brain AChE, 20 min after i.p. injection, (+/-)-huprine Y being more potent than (+/-)-huprine Z [ID(50) 1.09 (0.39-2.98) vs. 5.77 (3.29-10.30) micromol/kg]. The time-course study of the inhibitory effect displayed a t(1/2) of 1 h for the two compounds. These results show that these drugs are two potent, central AChE inhibitors of potential interest in the treatment of AD.     

Hepatitis C virus core protein transactivates the inducible nitric oxide synthase promoter via NF-kappaB activation

Intrahepatic levels of the inducible nitric oxide synthase (iNOS) are increased in chronic hepatitis C patients. As iNOS gene promoter contains Nuclear Factor (NF)-kappaB binding sites and hepatitis C virus (HCV) core protein activates NF-kappaB, the aim of this work was to study if HCV core protein transactivates iNOS promoter through NF-kappaB activation. iNOS mRNA and protein were determined by RT-PCR and western blot in HepG2 cells. The effect of HCV core protein on iNOS promoter was assayed by cotransfecting HepG2 cells with the core protein expression plasmid pHCV-Co and p1iNOS-CAT or p2iNOS-CAT plasmids. Formation of NF-kappaB-DNA complexes was determined by electrophoretic mobility shift assay. Transfection of HepG2 cells with pHCV-Co plasmid results in an increase in iNOS mRNA and protein levels. Cotransfection with pHCV-Co and p1iNOS-CAT or p2iNOS-CAT plasmids results in a transactivation of iNOS promoter, the presence of the proximal NF-kappaB binding site in the promoter being sufficient for the transactivation. Furthermore, the HCV core protein increases the formation of complexes between NF-kappaB and its binding sequence in the iNOS promoter. The expression of the NF-kappaB inhibitor IKB reverts the effect of the HCV core protein on the iNOS promoter. In conclusion, HCV core protein transactivates iNOS gene promoter through NF-kappaB activation.     

Strategies for tumor immune escape

The interactions between the immune system and malignant cells play an important role in tumorigenesis. Evidence that tumors are immunogenic continues to accumulate. Although they frequently express antigens in a form recognizable by the host immune system, tumors commonly "escape" the immune response. Tumors may therefore progress by evolving variants that can evade immune responses or by developing other strategies to avoid immune control. The purpose of this review is to evaluate the current status of knowledge concerning these different tumor-escape strategies.     

Change of the weight/ foot area coefficient in relation to aggregation in Tarebia granifera

OBJECTIVE: To analyze specimens dispersion in a population of Tarebia granifera and its relationship with the change of morphometric parameters. METHODS: Two samplings by parcels including two types of substrata in opposite aggregation conditions were carried out, and the specimen abundance was compared between both samplings and substrata. The samples were stratified into classes according to shell height and for each of these the coefficient weight/foot-area was calculated and correlated with class size. It was experimentally evaluated whether specimens with a lower foot load had a better persistence in emerged substratum as well as the interaction between two class groups of shell height. RESULTS: The abundance difference between samplings was t=5.874 (p<0.001), and t=10.15 (p<0.001) between emerged rocky and sandy substrata, only under conditions of high aggregation where foot load decreases with the size for higher specimens (r=-0.98, p<0.05). Experimentally, the abundance of specimens of opposed sizes were mutually limited (r=-0.87, p<0.01), waves' height limits the abundance of smaller snails (r=-0.94, p<0.01) but it is tolerated by larger ones (r=0.72, p<0.05), and foot load diminishes with the waves' height (r=-0.93, p<0.001). CONCLUSIONS: Under high aggregation conditions larger specimens emigrate toward substratum of difficult capture by smaller ones, which are limited by the environment's mechanical influence. The decrease of foot load facilitates specimens' dispersion.     

Surgical treatment of complicated sigmoid diverticulitis: our experience

Traditionally, surgical sigmoid diverticular emergencies used to be treated in stages, but more recently there has been a trend towards definitive surgery with immediate resection plus anastomosis under certain conditions. The aim of this study was to define the morbidity and mortality of resection plus anastomosis with on-table antegrade irrigation and of the Hartmann procedure for complicated sigmoid diverticulitis in relation to the type of peritonitis and to the American Society of Anesthesiologists (ASA) grade of the patients. From April 1999 to April 2002, 38 emergency operations for complicated sigmoid diverticulitis were performed at the San Sebastiano Hospital in Caserta. Six patients underwent operations for obstructions and 32 for perforation (19 Hinchley stage III and 13 Hinchley stage IV). Surgical therapy for obstruction consisted in 4 resections plus anastomosis, 1 subtotal colectomy and 1 Hartmann procedure. Surgical therapy for perforation consisted in 14 resections plus anastomosis and 18 Hartmann procedures. There was 1 case (5%) of anastomotic dehiscence out of 19 primary anastomoses versus 2/19 surgical complications (10%) after the Hartmann procedure. The mortality amounted to 1 death out of 38 (2.6%) in a patient treated with the Hartmann procedure. Left-sided colonic obstruction should be treated by resection plus anastomosis or by subtotal colectomy for ASA II-III patients and by Hartmann's procedure for ASA IV-V patients. ASA II-III patients with localised or generalised non-faecal peritonitis should be treated by resection plus anastomosis, while a Hartmann procedure should be the reasonable option for generalised faecal peritonitis and for ASA IV-V patients with localised or generalised non-faecal peritonitis.