Is systemic treatment of osteoporosis and mandibular resorption possible?

It is argued that mandibular resorption can be considered as osteoporotic in nature. This calls for a systemic approach in its treatment. One aspect mostly neglected is the tendency of bone to bind calcium and phosphate ions. A direct measure for this tendency is the difference in pH between the bone extracellular fluid and blood plasma with octocalcium phosphate. Calculation of these degrees of saturation of about 2000 data of blood plasma compositions given in the literature learned that calcitonin injections, estrogen replacement and magnesium supplementation increase the tendency of bone to bind calcium and phosphate ions and, hence, should be used in the therapy of mandibular resorption and of bone resorption in general.     

The 5-HT1-like agonist sumatriptan has a significant effect in chronic tension-type headache

Subcutaneous treatment of chronic tension-type headache with 2 mg and 4 mg sumatriptan, a selective 5-hydroxytryptamine1-like receptor agonist, was compared with placebo in a double-blind crossover study of 36 patients. The effect was evaluated using a 6-point verbal relief rating scale and by visual analog scale ratings of headache intensity before and for 2 h after treatment. Sumatriptan induced a modest but significantly greater headache relief than placebo, whereas no significant difference was found between the two doses of sumatriptan. Headache relief following sumatriptan was significant after 60 min and still seemed to be increasing after 120 min when the examination terminated. Three possible mechanisms of action of sumatriptan in tension-type headache are discussed.     

ESR study of 13C-enriched carbonated calciumapatites precipitated from aqueous solutions

Summary The ESR spectrum of X-irradiated carbonated apatites precipitated from aqueous solutions was studied at carbonate contents ranging from approximately 5.4 up to 12.4 wt%. ¹²C- as well as ¹³C-enriched samples were prepared and examined with ESR after drying until constant weight at 25°C and 400°C. In these carbonated apatites, two CO₃ ^3- radicals were detected, one of which is derived from B-type carbonate situated at a phosphate lattice site. The other CO₃ ^3- most probably arises from CO₃ ^2- ions situated at OH^- lattice sites. In contradistinction to the B-type contribution, the A-type contribution to the overall ESR signal decreases in absolute terms with increasing carbonate concentration. In addition, the line shape and the complete set of principal g-values of the A1-signal found in previous studles could be determined, corroborating the assignment of A1 to a surface O^- ion.Research Associate of the N.F.S.R. (Belgium)     

Effect of Preemptive Nerve Block on Inflammation and Hyperalgesia after Human Thermal Injury

Background: Postoperative pain relief may be improved by reducing sensitization of nociceptive pathways caused by surgical trauma. Such a reduction may depend on the timing and efficacy of analgesia and the duration of the nociceptive block versus the duration of the nociceptive input. We examined whether a prolonged nerve block administered before a superficial burn injury could reduce local inflammation and late hyperalgesia after recovery from the block.

Methods: The effects of a preemptive saphenous nerve block on primary and secondary hyperalgesia, skin erythema, and blister formation, were compared to the opposite unblocked leg for 12 h after bilateral thermal injuries (15 x 25 mm, 49 degrees C for 5 min) in 20 healthy volunteers. Recovery from the block was identified by return of sensation to cold.

Results: Six subjects were excluded because of insufficient initial block (2 subjects) or because the block lasted beyond the study period (4 subjects). The remaining 14 subjects experienced significantly reduced primary (P = 0.005) and secondary hyperalgesia (P = 0.01) in the blocked leg after return of cold sensation compared to the unblocked leg. Erythema intensity and blister formation were not significantly affected by the blockade (P = 0.94 and P = 0.07, respectively).     

The contribution of CO3 3− and CO2 − to the ESR spectrum near g=2 of powdered human tooth enamel

Summary The ESR spectrum near g=2 of powdered human tooth enamel from upper central incisors and lower canines was studied as a function of microwave power, irradiation, and storage time. The results clearly demonstrate that the ESR spectrum is composite with at least five paramagnetic species contributing to the signal. The main stable component is assigned to CO₂ ⁻. Two other components arise from CO₃ ³⁻ radicals, one of which is demonstrated to be the same center as is present on a phosphate site in sodium- and carbonate-containing calciumapatite.     

Dolomite as a possible magnesium-containing phase in human tooth enamel

Summary A solid-state chemical model is derived to estimate the solubility of dolomites having different degrees of cation ordering. It is shown that the solubility of dolomites formed by precipitation at ordinary temperatures is such that it allows for the formation of dolomite in tooth enamel duringin vivo mineralization.     

A novel subject synchronization clinical trial design for Alzheimer's disease

One of the challenges in developing a viable therapy for Alzheimer's disease has been demonstrating efficacy within a clinical trial. Using this as motivation, we sought to re-examine conventional clinical trial practices in order to determine whether efficacy can be better shown through alternative trial designs and novel analysis methods. In this work, we hypothesize that the confounding factors which hamper the ability to discern a treatment signal are the variability in observations as well as the insidious nature of the disease. We demonstrate that a two-phase trial design in which drug dosing is administered after a certain level of disease severity has been reached, coupled with a method to account more accurately for the progression of the disease, may allow us to compensate for these factors, and thus enable us to make treatment effects more apparent. Utilizing data from two previously failed trials which involved the evaluation of galantamine for indication in mild cognitive impairment, we were able to demonstrate that a clear treatment effect can be realized through both visual and statistical means, and propose that future trials may be more likely to show success if similar methods are utilized.     

Hepatitis C virus expressing flag-tagged envelope protein 2 has unaltered infectivity and density, is specifically neutralized by flag antibodies and can be purified by affinity chromatography

Hepatitis C virus (HCV) purification by ultracentrifugation is difficult because of the low and heterogeneous density of native and cultured viruses. It was recently shown that inserting flag tag into envelope protein 2 (E2) of HCV permitted virus purification by affinity chromatography. However, flag-tagged viruses had drastically altered properties, and purification yield was low. In this study, we found that insertion of flag tag at the N-terminus of E2 in HCV recombinant J6/JFH1 did not affect viability in Huh7.5 cells, and that flag-tagged virus had physiochemical properties similar to the original virus. Flag-tagged virus was susceptible to flag-specific antibody neutralization, and infected cells could be immuno-stained by anti-flag antibodies. Using affinity chromatography with anti-flag resin we repeatedly obtained ~ 30% recovery of infectious particles. The full viability and unaltered physiochemical properties of flag-tagged HCV is an important improvement for utilizing these viruses for imaging, virion composition analysis and possibly vaccine development.     

Population pharmacokinetic analysis of tacrolimus in the first year after pediatric liver transplantation

Purposes

Tacrolimus (TAC) is the most widely used immunosuppressant for the prevention of acute rejection after solid organ transplantation. Its pharmacokinetics (PK) show considerable variability, making TAC a good candidate for therapeutic drug monitoring (TDM). The principal aim of the study was to describe the PK of TAC in pediatric patients during the first year after transplantation.

Methods

Routine TDM trough levels of TAC were obtained from 42 pediatric liver allograft recipients during the first year after transplantation. A population PK model was developed using nonlinear mixed-effects modeling to describe TAC PK during this period and to explain the observed variability by means of patients’ demographics, biochemical test results and physiological characteristics.

Results

The PK of TAC were best described by a two-compartment model with first-order elimination. Apparent volumes of the central compartment, intercomparmental clearance and maximum blood clearance estimates were 253 L, 115 L/day and 314 L/day, respectively. The absorption first-order rate and volume of peripheral compartment were fixed to 4.5 h^-1 and 100 L, respectively. While hematocrit levels, time after transplantation and bodyweight influenced TAC clearance, bodyweight was the only covariate retained on volume of distribution.

Conclusions

We developed a TAC population PK model in pediatrics covering the first year after liver transplantation that may serve as a tool for TAC dose individualization as part of TDM.     

Comparative oral bioavailability of non-fixed and fixed combinations of artesunate and amodiaquine in healthy Indian male volunteers

Objective  

The aim of the present study was to compare the pharmacokinetic properties, bioavailability and tolerability of artesunate (AS) and amodiaquine (AQ) administered as a fixed-dose combination (Amonate FDC tablets; Dafra Pharma, Turnhout, Belgium) or as a non-fixed dose combination of separate AS tablets (Arsuamoon; Guilin Pharmaceutical Co, Shanghai, China) and AQ tablets (Flavoquine; Sanofi-Aventis, Paris, France).