Implanted bisphosphonates in bone cement affect bone markers in rat serum

Purpose

Bisphosphonates (BPs) are antiresorptive drugs that provide important effects on bone turnover. The key to the high efficiency of BPs is their affinity for bone tissue, and their chemical structure provides their molecular mechanism of action. BPs are widely used to treat a variety of diseases that cause excess bone resorption, such as bone metastasis, hypercalcaemia due to malignancy and Paget’s disease. The goal of this study was to assess whether the bisphosphonate (Pamifos®) present in bone cement has any effect on bone turnover. In this paper, we present changes in cytokine levels in the serum of rats treated surgically.

Methods

Research was performed on 40 adult male Wistar rats. The rats were divided into four groups: two control groups (A, B) and two experimental groups (C, D). Bone in rats in the experimental groups was implanted with BP-enriched cement, whereas bone in control-groups rats was implanted with clean cement (without BPs).

Results

We found a higher concentration of tumour necrosis factor alpha (TNF-α) three weeks after surgery in rats implanted with BP-enriched cement compared with rats implanted with clean cement. After six weeks of treatment, TNF-α levels decreased significantly in rats treated with BP-enriched cement, whereas the control group experienced an increase in TNF-α. The concentration of osteoprotegerin ligand (OPG) was higher in rats with BP implants. We found high levels of receptor activator of nuclear factor kappa-B ligand (RANKL) in rats after implantation of cement without BP in both groups.

Conclusions

We conclude that use of bisphosphonate (Pamifos®), which is present in bone cement, has an effect on bone turnover in that BPs stimulate an increase in OPG and a decrease in RANKL in the bone microenvironment and thus may be an important component of mechanisms that reduce bone resorption. Therefore, the use of BP-enriched cement implants appears to be justified.     

Early results of treatment for congenital clubfoot using the Ponseti method

The purpose of this study was to evaluate the early results of the Ponseti method in reducing extensive corrective surgery rates for congenital idiopathic clubfoot in patients treated in Children's Orthopaedic Clinic and Rehabilitation Department Medical University of Lublin between the years 2007-2011. Thirty-five patients with 47 idiopathic clubfeet were followed prospectively while being managed with the Ponseti method. Clubfoot severity was graded with use of the Dimeglio system. The initial correction was achieved, and early results were measured by using Pirani scoring method.     

A general approach for postmortem interval based on uniformly distributed and interconnected qualitative indicators

There are many qualitative indicators for postmortem interval (PMI) of human or animal cadavers. When such indicators are uniformly spaced over PMI, the resultant distribution may be very useful for the estimation of PMI. Existing methods of estimation rely on indicator persistence time that is, however, difficult to estimate because of its dependence on many interacting factors, of which forensic scientists are usually unaware in casework. In this article, an approach is developed for the estimation of PMI from qualitative markers in which indicator persistence time is not used. The method involves the estimation of an interval preceding appearance of a marker on cadaver called the pre-appearance interval (PAI). PMI is delineated by PAI for two consecutive markers: the one being recorded on the cadaver (defining lower PMI) and the other that is next along the PMI timeline but yet absent on the cadaver (defining upper PMI). The approach was calibrated for use with subsequent life stages of carrion insects and tested using results of pig cadaver experiments. Results demonstrate that the presence and absence of the subsequent developmental stages of carrion insects, coupled with the estimation of their PAI, gives a reliable and easily accessible knowledge of PMI in a forensic context.

     

Rokitansky-Kustner-Hauser syndrome - a case report.

Rokitansky-Kuster-Hauser syndrome, also called utero-vaginal aplasia, was first described at the beginning of the 19th century by Mayer (1829). It affects 1.2 % of girls and consists of a complete absence of the vagina with severe developmental anomalies of the uterus. Most often it consists of rudimentary cornua uteri, a normal female karyotype 46 XX and secondary female sexual characteristics.     

Evidence for the promotion of bone mineralization by 1alpha,25-dihydroxycholecalciferol in the rat unrelated to the correction of deficiencies in serum calcium and phosphorus.

Concurrent administration of 1alpha,25-dihydroxycholecalciferol [1alpha,25-(OH)2-CC] to intact and thyroparathyroidectomized rats treated with ethane-1-hydroxy-1,1-diphosphonate (EHDP) prevented or reversed the EHDP-induced inhibition of bone mineralization as measured by changes in epiphyseal plate width and ash content of bone. An analog, 1alpha-droxycholecalciferol, was also effective. Recovery of bone after EHDP treatment was also significantly improved by administration of 1alpha,25-(OH)2-CC as evidenced by enhanced uptake of 45Ca by epiphyseal plates and decreased plate widths. Cholecalciferol (CC), ergocalciferol, dihydrotachysterol2, 5,6-trans-CC, 25-OH-CC, 5,6-Trans-25-OH-CC, and 1alpha24R,25-(OH)3-CC also blocked EHDP-induced epiphyseal plate widening, but required high, pharmacological dose levels. 24R,25- (OH)2-CC was inactive at doses up to 10 microgram/day. Since EHDP-treated rats are not deficient in calcium or phosphate, these data suggest that 1alpha,25-dihydroxycholecalciferol promoted bone mineralization independently of effects upon the intestinal absorption of calcium and phosphate.     

Determination of rofecoxib, a cyclooxygenase-2 specific inhibitor, in human plasma using high-performance liquid chromatography with post-column photochemical derivatization and fluorescence detection.

A method for the determination of rofecoxib in human plasma is described. After the addition of an internal standard, buffered (pH 5) plasma samples are extracted with hexane-methylene chloride (50:50, v/v). The extracts are evaporated to dryness and reconstituted in mobile phase. Upon exposure to UV light, the analyte was found to undergo a stilbene-phenanthrene-like photocyclization reaction with the resulting formation of a highly fluorescent species. Thus, the plasma extracts were analyzed via HPLC with post-column photochemical derivatization and fluorescence detection. The assay has been validated in the concentration range of 0.5-100 ng/ml using 1-ml samples. The method has been successfully utilized to support human clinical pharmacokinetic studies.     

Types of fractures of the proximal part of the ulna bone in children and youth

In this paper, authors present the forms of fractures of proximal part of ulna bone. Research is based on the completed data of 34 child and young patients in the age of 9–17 years treated in the Clinic of Pediatric Surgery and Traumatology, Medical University of Lublin and Clinic of Traumatology, Medical University of Lublin, in the years 1986–2005. In those years we had 1,048 children and youth with various elbow’s fractures in age between 4 and 17 years. Fractures have been singled out according to the age and gender as well as the side of the fracture. In our material, we separated two main types of injuries of the proximal part of the ulna bone on the basis of the analysis of the course of the crack in the fracture which is the main difference from fractures of proximal part of ulna bone in older patients where we have an occasion to meet plenty of various forms of injuries predominately caused by higher energy. We proposed unambiguous naming of these childhood injuries on the strength of international anatomical nomenclature. During statistic analysis the relationships between the number of individual forms of fractures and the patient’s development period have been shown. We did not find a crucial statistical relationship between the development period and side of the fracture and any essential relationship between development period and gender of our patients. We affirmed that in the treatment of those kinds of fractures surgical methods predominate. Taking into account the presented results of applied treatment, we would like to emphasize the specificity of child’s skeletal system and risk of appearance of severe complications in case of inappropriate medical proceedings.     

Disposition and pharmacokinetics of the antimigraine drug, rizatriptan, in humans.

The absorption and disposition of rizatriptan (MK-0462, Maxalt(TM)), a selective 5-HT(1B/1D) receptor agonist used in the treatment of migraine headaches, was investigated in humans. In a two-period, single i.v. (3 mg, 30-min infusion), and single oral (10 mg) dose study with [(14)C]rizatriptan in six healthy human males, total recovery of radioactivity was approximately 94%, with unchanged rizatriptan and its metabolites being excreted mainly in the urine (89% i.v. dose, 82% p.o. dose). Approximately 26 and 14% of i.v. and oral rizatriptan doses, respectively, were excreted in urine as intact parent drug. In a second, high-dose study (60 mg p.o.), five metabolites excreted into urine were identified using liquid chromatography-tandem mass spectrometry and NMR methods. They were triazolomethyl-indole-3-acetic acid, rizatriptan-N(10)-oxide, 6-hydroxy-rizatriptan, 6-hydroxy-rizatriptan sulfate, and N(10)-monodesmethyl-rizatriptan. Urinary excretion of triazolomethyl-indole-3-acetic acid after i.v. and oral administrations of rizatriptan accounted for 35 and 51% of the dose, respectively, whereas the corresponding values for rizatriptan-N(10)-oxide were 4 and 2% of the dose. Plasma clearance (CL) and renal clearance (CL(r)) were 1325 and 349 ml/min, respectively, after i.v. administration. A similar CL(r) value was obtained after oral administration (396 ml/min). The primary route of rizatriptan elimination occurred via nonrenal route(s) (i.e., metabolism) because the CL(r) of rizatriptan accounted for 25% of total CL. Furthermore, the CL(r) was higher than normal glomerular filtration rate ( approximately 130 ml/min), indicating that this compound was actively secreted by renal tubules. The absorption of rizatriptan was approximately 90%, but it experienced a moderate first-pass effect, resulting in a bioavailability estimate of 47%.