Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GN

Severe GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti–glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN.     

Effect of sandblasting on fracture load of titanium ceramic crowns

Purpose of the Study:

It is difficult to achieve a reliable bond between the titanium and veneering porcelain. The aim of this study was to evaluate the bond strength between titanium ceramic crowns.

Materials and Methods:

The surfaces of titanium copings were divided in two groups. Group A sandblasted with 250 um (n = 10) and Group B without sandblasting (n = 10). Low-fusing porcelain was bonded over copings. A universal testing machine was used to determine the fracture load (N) of the crowns. All data were compared using Student''s t-test.

Results:

There was a significant difference in fracture toughness between two groups (P = 0.05). The mean value of fracture strength for Group A was 721.66 N and for Group B was 396.39 N.

Conclusions:

Sandblasting improves the bond strength between titanium, and ceramic, mechanical bonding plays a crucial role in the bonding between titanium and ceramic.Key Words: Bonding, fracture load, sandblasting, titanium     

Antiplasmodial activity-aided isolation and identification of quercetin-4’-methyl ether in Chromolaena odorata leaf fraction with high activity against chloroquine-resistant Plasmodium falciparum

The present study was undertaken to evaluate the antiplasmodial activity of Chromolaena odorata leaf extract and gradient fractions through in vivo and in vitro tests, aimed at identifying its antiplasmodial constituents. Sub-fractions obtained from the most active gradient fraction were further tested for cytotoxicity against THP-1 cells, chloroquine-sensitive (HB3) and chloroquine-resistant (FCM29) Plasmodium falciparum. Our results showed the dichloromethane gradient fraction was most effective, significantly (P?50 of 4.8 and 6.74 μg/ml against P. falciparum HB3 and FCM29, respectively. Cytotoxicity of DF11 was estimated to be above 50 μg/ml, and its separation by column chromatography yielded a flavonoid which was characterized as 3, 5, 7, 3’ tetrahydroxy-4’-methoxyflavone from its spectroscopic data. It significantly suppressed infection (65.43–81.48 %) in mice at 2.5–5 mg/kg doses and compared favourably with the effects of chloroquine and artemisinin. It may therefore serve as a useful phytochemical and antiplasmodial activity marker of C. odorata leaves, which exhibit potential for development as medicine against malaria.     

Neonatal Severe Hyperparathyroidism due to Compound Heterozygous Mutation of Calcium Sensing Receptor (CaSR) Gene Presenting as Encephalopathy

The authors report a 14-d-old neonate who presented with lethargy, polyuria and dehydration and was found to have severe hypercalcemia with hyperparathyroidism. This neonate was treated with saline hydration, diuresis and injection pamidronate. Genetic analysis revealed a compound heterozygous mutation of CaSR.     

Reuse of explanted permanent pacemakers donated by funeral homes

Poor patients in developing countries may not receive permanent pacemakers (PPMs) even as lifesaving measures because of their high cost. In this report we examined whether PPMs that were explanted and donated by funeral homes in the United States could be safely and effectively reused in indigent patients in India. With permission from the deceased patients' families, 121 PPMs were explanted and donated by funeral homes for reuse. These PPMs were sterilized and sent for implantation in needy and indigent patients at a charity hospital in Mumbai, India. From the pool of donated 121 PPMs, 53 (88%, 11 single-chamber PPMs, 21%, and 42 dual-chamber PPMs, 79%) were acceptable for reuse and implanted (37 new implants, 70%, and 16 for battery/generator replacement, 30%) in 53 patients (mean ± SD 64 ± 10 years old, 28 women, 53%). Indications for PPM implantation were complete heart block (n = 27, 51%) and sick sinus syndrome (n = 26, 49%). All patients were alive and well postoperatively. No significant complications including infections or device failures occurred over 19 to 1,827 days (mean 661) of follow-up. Of 40 patients (75%) who were followed locally, 4 (10%) died because of nonpacemaker-related causes; time to death was 121 to 750 days (mean 430) after PPM implantation. All except 2 patients (5%) reported marked improvement in their symptoms. There were only 4 patients (8%) who were previously employed, and all were able to resume their manual labor work. Also, of the women, 27 patients (96%) reported improvement in symptoms enabling them to resume regular household chores as housewives after PPM implantation. In conclusion, with proper device sterilization and handling protocols, reuse of explanted PPMs in poor patients in developing countries is safe and effective. Implantation of donated PPMs can not only save lives but also improve quality of life of needy poor patients.