Bioabsorbable materials in orthopaedics

The applications of bioabsorbable implants in orthopaedic surgery have mainly been mandated from the need to eliminate implant removal operations. Although they have not gained widespread popularity among orthopaedic surgeons, they still represent an area of evolution. Considerable effort has been put into developing new bioabsorbable materials with fewer adverse effects. In this article an extensive review of the literature is presented emphasising on basic science and clinical applications of these materials. A review of the types of implants, the materials used, their biochemical properties, their adverse effects and some of the potential future applications is presented.     

Melanin concentrating hormone is a novel regulator of islet function and growth

Melanin concentrating hormone (MCH) is a hypothalamic neuropeptide known to play a critical role in energy balance. We have previously reported that overexpression of MCH is associated with mild obesity. In addition, mice have substantial hyperinsulinemia and islet hyperplasia that is out of proportion with their degree of obesity. In this study, we further explored the role of MCH in the endocrine pancreas. Both MCH and MCHR1 are expressed in mouse and human islets and in clonal beta-cell lines as assessed using quantitative real-time PCR and immunohistochemistry. Mice lacking MCH (MCH-KO) on either a C57Bl/6 or 129Sv genetic background showed a significant reduction in beta-cell mass and complemented our earlier observation of increased beta-cell mass in MCH-overexpressing mice. Furthermore, the compensatory islet hyperplasia secondary to a high-fat diet, which was evident in wild-type controls, was attenuated in MCH-KO. Interestingly, MCH enhanced insulin secretion in human and mouse islets and rodent beta-cell lines in a dose-dependent manner. Real-time PCR analyses of islet RNA derived from MCH-KO revealed altered expression of islet-enriched genes such as glucagon, forkhead homeobox A2, hepatocyte nuclear factor (HNF)4alpha, and HNF1alpha. Together, these data provide novel evidence for an autocrine role for MCH in the regulation of beta-cell mass dynamics and in islet secretory function and suggest that MCH is part of a hypothalamic-islet (pancreatic) axis.     

The effects of age on the incidence of aneuploidy rates in spermatozoa of oligoasthenozoospermic patients and its relationship with ICSI outcome

The development of intracytoplasmic sperm injection (ICSI) for treatment of infertility as a result of severe male factor has improved the chances of achieving pregnancy in many infertile couples. However, concerns have been raised regarding the safety of this technique, because natural sperm selection is bypassed. In the present study, 25 oligoasthenozoospermic patients who were divided into two groups according to age: group A, 20-34 (n = 10) and group B, 35-50 (n = 15), were included. Pooling the data of the three semen parameters that were tested (volume, concentration and progressive motility) no statistically significant difference between the two age groups was found. A total of 50 883 decondensed spermatozoa was analysed using the dual and triple colour fluorescence in situ hybridization to estimate the rates of aneuploidy for chromosomes 13, 18, 21, X and Y in the two age groups. There was a significantly higher incidence of disomy for chromosome 21 compared to the other autosomes (chromosomes 13 and 18) in both age groups. The disomy rate of XY was significantly higher in the younger subject group (0.1%) compared to the older group (0.05%, p < 0.05). Statistically significant differences in the mean number of clinical pregnancies and abortions were not observed between the two age groups. The aneuploidy rates for all the analysed chromosomes did not differ significantly, both between and within the two age groups, and as a result there seems to be no effect of male age on chromosome numbers in the spermatozoa and on the ICSI outcome.     

Fibrin sealant promotes migration and proliferation of human articular chondrocytes: possible involvement of thrombin and protease-activated receptors

Fibrin sealant (FS), a biological adhesive material, has been recently recommended as an adjunct in autologous chondrocyte implantation (ACI). While FS has been shown to possess osteoinductive potential, little is known about its effects on chondrogenic cells. In this study, we assessed the bioactivity of FS (Tisseel) on the migration and proliferation of human articular chondrocytes in vitro. Using a co-culture assay to mimic matrix-induced ACI (MACI), chondrocytes were found to migrate from collagen membranes towards FS within 12 h of culture, with significant migratory activity evident by 24 h. In addition, 5-bromo-2'-deoxyuridine (BrdU) incorporation experiments revealed that thrombin, the active component of the tissue glue, stimulated chondrocyte proliferation, with maximal efficacy observed at 48 h post-stimulation (1-10 U/ml). In an effort to elucidate the molecular mechanisms underlying these thrombin-induced effects, we examined the expression and activation of protease-activated receptors (PARs), established thrombin receptors. Using a combination of RT-PCR and immunohistochemistry, all four PARs were detected in human chondrocytes, with PAR-1 being the major isoform expressed. Moreover, thrombin and a PAR-1, but not other PAR-isotype-specific peptide agonists, were found to induce rapid intracellular Ca2+ responses in human chondrocytes in calcium mobilization assays. Together, these data demonstrate that FS supports both the migration and proliferation of human chondrocytes. We propose that these effects are mediated, at least in part, via thrombin-induced PAR-1 signalling in human chondrocytes.     

Serum and cerebrospinal fluid concentrations of linezolid in neurosurgical patients

Linezolid is a new antimicrobial agent effective against drug-resistant gram-positive pathogens commonly responsible for central nervous system (CNS) infections in neurosurgical patients hospitalized in intensive care units. In order to study the penetration of this antimicrobial into the cerebrospinal fluid (CSF) of such patients, the disposition of linezolid in serum and CSF was studied in 14 neurosurgical patients given linezolid at 600 mg twice daily (1-h intravenous infusion) for the treatment of CNS infections caused by gram-positive pathogens or for prophylactic chemotherapy. Serum and CSF linezolid steady-state concentrations were analyzed by high-pressure liquid chromatography, and the concentration-time profiles obtained were analyzed to estimate pharmacokinetic parameters. The mean +/- standard deviation (SD) linezolid maximum and minimum measured concentrations were 18.6 +/- 9.6 microg/ml and 5.6 +/- 5.0 microg/ml, respectively, in serum and 10.8 +/- 5.7 microg/ml and 6.1 +/- 4.2 microg/ml, respectively, in CSF. The mean +/- SD areas under the concentration-time curves (AUCs) were 128.7 +/- 83.9 microg x h/ml for serum and 101.6 +/- 59.6 microg x h/ml for CSF, with a mean penetration ratio for the AUC for CSF to the AUC for serum of 0.66. The mean elimination half-life of linezolid in CSF was longer than that in serum (19.1 +/- 19.0 h and 6.5 +/- 3.6 h, respectively). The serum and CSF linezolid concentrations exceeded the pharmacodynamic breakpoint of 4 microg/ml for susceptible target pathogens for the entire dosing interval in the majority of patients. These findings suggest that linezolid may achieve adequate concentrations in the CSF of patients requiring antibiotics for the management or prophylaxis of CNS infections caused by gram-positive pathogens.     

p62 ubiquitin binding-associated domain mediated the receptor activator of nuclear factor-kappaB ligand-induced osteoclast formation: a new insight into the pathogenesis of Paget's disease of bone

Paget's disease of bone (PDB) is a debilitating bone disorder characterized by giant osteoclasts, enhanced bone destruction, and irregular bone formation. Recently, mutations in SQSTM1 (also known as p62) have been detected in PDB sufferers, with all mutations resulting in either loss of function or truncation/deletion of the ubiquitin binding-associated (UBA) domain. We hypothesized that mutation in the p62 gene resulting in either deletion or premature termination of the UBA domain accounts for the elevated osteoclastic formation and bone resorption associated with PDB. Remarkably, overexpression of the p62 UBA domain deletion mutant (p62DeltaUBA) significantly enhanced osteoclastogenesis in vitro compared to cells expressing either wild-type p62 (p62WT) or a control vector in a RAW264.7 osteoclastogenic system. Overexpression of p62DeltaUBA potentiated the formation of abnormally large multinucleated osteoclasts and resorption of bone, reminiscent of PDB. Consistent with the enhancement of osteoclastogenesis, overexpression of p62DeltaUBA potentiated receptor activator of nuclear factor-kappaB ligand-induced activation of nuclear factor-kappaB, NFAT, and ERK phosphorylation. Furthermore, as determined by confocal microscopy, deletion of the p62 UBA domain impaired the association of p62 with TRAF6 in the proteasomal compartment. These results suggest that the UBA domain encodes essential regulatory elements required for receptor activator of nuclear factor-kappaB ligand-induced osteoclast formation and bone resorption that may be directly associated with the progression of PDB.     

Ruptured hemangioma of the umbilical cord and intrauterine fetal death, with review data

A case of intrauterine fetal death with rupture of a hemangioma in the umbilical cord is presented. Hemangiomas are uncommon tumors of the umbilical cord, and their clinical significance is not entirely clear, but associations with polyhydramnios, fetal disseminated intravascular coagulation, and fetal hydrops have been described. In a high proportion of the umbilical cord hemangiomas reported in the literature (32 cases), the fetus had died in utero as in the present case and only ten cases were vital and completely normal infants. Associated malformations and complications of the umbilical cord hemangioma are reviewed.     

SPECT neuroimaging and neuropsychological functions in different stages of Parkinson’s disease

Purpose  

The present study investigated differences and associations between cortical perfusion, nigrostriatal dopamine pathway and neuropsychological functions in different stages of Parkinson’s disease (PD).