Parallel conduction of the phase I preventive and therapeutic trials based on the Tat vaccine candidate.

The native HIV-1 Tat protein was chosen as vaccine candidate for phase I clinical trials in both uninfected (ClinicalTrials.gov identifier: NCT00529698) and infected volunteers (ClinicalTrials.gov identifier: NCT00505401). The rationale was based on the role of Tat in the natural infection and AIDS pathogenesis, on the association of Tat-specific immune responses with the asymptomatic stage and slow-progression rate as well as on its sequence conservation among HIV clades (http://www.hiv1tat-vaccines.info/). The parallel conduction in the same clinical centers of randomized, double blind, placebo-controlled phase I studies both in healthy, immunologically competent adults and in HIV-infected, clinically asymptomatic, individuals represents a unique occasion to compare the vaccine-induced immune response in both the preventive and therapeutic setting. In both studies, the same lot of the native Tat protein was administered 5 times, every four weeks, subcute (SC) with alum adjuvant or intradermic (ID), in the absence of adjuvant, at 7.5 microg, 15 microg or 30 microg doses, respectively. The primary and secondary endpoints of these studies were the safety and immunogenicity of the vaccine candidate, respectively. The study lasted 52 weeks and monitoring was conducted for on additional 3 years. The results of both studies indicated that the Tat vaccine is safe and well tolerated both locally and systemically and it is highly immunogenic at all the dosages and by both routes of administration. Vaccination with Tat induced a balanced immune response in uninfected and infected individuals. In particular, therapeutic immunization induced functional antibodies and partially reverted the marked Th1 polarization of anti-Tat immunity seen in natural infection, and elicited a more balanced Th1/Th2 immune response. Further, the number of CD4 T cells correlated positively with anti-Tat antibody titers. Based on these results, a phase II study is ongoing in infected drug-treated individuals (http://www.hiv1tat-vaccines.info/).

Leaf sheath cuticular waxes on bloomless and sparse-bloom mutants of Sorghum bicolor.

Leaf sheath cuticular waxes on wild-type Sorghum bicolor were approximately 96% free fatty acids, with the C28 and C30 acids being 77 and 20% of these acids, respectively. Twelve mutants with markedly reduced wax load were characterized for chemical composition. In all of the 12 mutants, reduction in the amount of C28 and C30 acids accounted for essentially all of the reduction in total wax load relative to wildtype. The bm2 mutation caused a 99% reduction in total waxes. The bm4, bm5, bm6, bm7 and h10 mutations caused more than 91% reduction in total waxes, whereas the remaining six mutants, bm9, bm11, h7, h11, h12 and h13, caused between 35 and 78% reduction in total wax load. Relative to wild-type, bm4 caused a large increase in the absolute amount of C22, C24 and C26 acids, and reduction in the C28 and longer acids, suggesting that bm4 may suppress elongation of C26, acyl-CoA primarily. The h10 mutation increased the absolute amounts of the longest chain length acids, but reduced shorter acids, suggesting that h10 may suppress termination of acyl-CoA elongation. The bm6, bm9, bm11, h7, h11, h12 and h13 mutations increased the relative amounts, but not absolute amounts, of longer chain acids. Based on chemical composition alone, it is still uncertain which genes and their products were altered by these mutations. Nevertheless, these Sorghum cuticular wax mutants should provide a valuable resource for future studies to elucidate gene involvement in the biosynthesis of cuticular waxes, in particular, the very-long-chain fatty acids.

Postoperative right atrial and pulmonary embolism after prolonged spinal surgery.

Perioperative pulmonary thromboembolism can proceed rapidly with grave prognosis, in which immediate or accurate diagnosis and management is not easy. According to the literatures, patients receiving spinal surgery are at relatively lower risk of developing thromboembolism. We would like to present a case of postoperative pulmonary thromboembolism which developed after a prolonged lumbar spinal surgery. Tachycardia and unstable hemodynamics were noted postoperatively. Pulmonary and right atrial thrombi were disclosed by transesophageal echocardiography. Although cardiotomy and thrombectomy were immediately performed, the patient finally died 3 days after the operation. The pathogenesis of venous thromboembolism (VTE) in the surgical patients, the risk factors which predispose a patient to VTE, diagnosis, and treatment as well as the prophylactic measures of VTE are herein reviewed and discussed.

Clearance of sodium lauryl sulphate from the oral cavity.

Sodium lauryl sulphate (SLS) is used in toothpaste and mouth rinses as an emulsifying and surface cleaning agent. SLS has been implicated in an increased incidence of oral irritation in subjects predisposed to recurrent aphthous stomatitis (RAU). Hence, the purpose of this study was to determine the levels of SLS found in the oral cavity following rinsing with an SLS containing mouth rinse and brushing with a SLS containing dentifrice. An analytical method to separate SLS from saliva and other complex systems was developed. The method used high performance liquid chromatography (HPLC) and detection performed using conductivity measurements. Standard curves with known concentrations showed a detection limit of less than 0.4 ug SLS/ml of fluid. 2 clinical studies were conducted to determine the amount of SLS retained in the mouth by a healthy population after rinsing or brushing with commercially available products. The results showed, after rinsing, that 96% of the available SLS from the rinse was recovered in the collected samples within 2 min. Similarly, after brushing, 86% of the SLS contained within the toothpaste was recovered from the collected samples within the first 10 min. These results showed that the amount of SLS retained in the oral cavity was minimal and the contact time between SLS and the oral cavity was very short. A 2nd study was conducted to measure the amount of SLS retained in the mouth by a population susceptible to RAU. After rinsing, 97% of the available SLS was recovered within the first 2 min. Following brushing, 89% of the SLS in the dentifrice was recovered within the first 10 min. These results were comparable to those determined by the study involving the healthy population.

Intra-oral remineralization of enamel with a MFP/DCPD and MFP/silica dentifrice using surface microhardness.

The present study was undertaken to ascertain the effect of dicalcium phosphate dihydrate (DCPD) abrasive in a dentifrice on the remineralizaton of enamel using a surface microhardness technique. The method of assessing enamel remineralization via surface microhardness (SMH) was validated in a randomized, crossover, double-blind, intra-oral remineralization study conducted with 12 healthy adults. Enamel demineralization was achieved in vitro by covering bovine enamel blocks with exogenous oral bacteria, S. Mutans 1600 Ingbritt, containing glucan which was then exposed to sucrose. In the intra-oral treatment phase, subjects were fitted with oral maxillary palatal retainers, each holding four demineralized enamel blocks. Subjects brushed their teeth for 30 seconds with a test dentifrice, swished for an additional 60 seconds, rinsed with water and then retained the blocks intra-orally for 4 hours. Percent mineral recovery for each enamel block was calculated as the ratio of the changes in enamel microhardness due to treatment (remin) and sucrose challenge (demin). Treatments included DCPD-based dentifrices containing 0, 250 and 1000 ppm fluoride (F) from sodium monofluorophosphate (MFP). Using SMH, respective mean percent mineral recoveries of 5.7, 18.7 and 41.4% were obtained. All ADA criteria for model validation were fulfilled. This same model was then used to compare the remineralization effects of a silica placebo, DCPD placebo, 1000 ppm F MFP/silica and 1000 ppm F MFP/DCPD dentifrice. Mean percent mineral recoveries of -0.9, 24.1, 30.2 and 55.7% were obtained, respectively. The MFP/DCPD dentifrice was superior to MFP/silica (<0.01) with use of the MFP/DCPD dentifrice when compared to MFP/silica or the silica placebo. These results indicate that more active calcium and a higher degree of saturation (DS(EN)) with respect to enamel exists for an extended period of time after use of a MFP/DCPD dentifrice. Since an elevation in DS(EN) is considered a major parameter controlling the extent of enamel remineralization, this finding may partly explain the superior remineralization of enamel observed with the MFP/DCPD dentifrice. The significant increases in calcium activity and intra-oral enamel remineralization by the DCPD-based dentifrice are consistent with earlier findings that a DCPD abrasive provides added benefit for enamel remineralization.