Squeaking and other noises in patients with ceramic-on-ceramic total hip arthroplasty.

INTRODUCTION: Noise in ceramic-on-ceramic (CoC) total hip arthroplasty (THA) is a potential symptom of abnormal bearing wear. Squeaking and other prosthetic hip noises are multi-factorial phenomena that can be analysed and may provide prognostic information. METHODS: 46 patients with noisy CoC bearings were investigated using X-ray, computed tomography and joint fluid analysis, and classified into either high or low risk of ceramic liner fracture groups according to previously published guidelines. Noise events from the bearings of 16 high risk cases which were subsequently revised were compared with 30 patients in the low risk control group who did not undergo revision. Noise events were analysed for their physical characteristics using a standardised protocol and classified as either low frequency and short duration 'clicking' or long duration and high frequency 'squeaking'. RESULTS: The peak frequency of squeaking during forward walking was significantly higher for patients in the case group who were revised, compared with the control group. The patient-reported onset of squeaking (46 months postoperatively) was earlier than short-noise emissions (82 months). In the standardised sequence of movements, short-noise always occurred more frequently than squeaking. Small heads (28 mm) were more likely to develop short-noise, while large heads (⩾32 mm) were more likely to develop squeaking. DISCUSSION: Noise evaluation may provide additional value for predicting failure of CoC bearings, though some questions should be better investigated in a dedicated prospective trial.

Ischemia-Modified Albumin Expression: Is there a Difference between Male and Female Subjects?

BACKGROUND: Ischemia-modified albumin (IMA) derives from naive albumin, modified in the binding region of bivalent ions, as cobalt and iron. The cobalt, released from some types of hip prosthesis seems to be metabolized differently in males and females but the iron ion is more prevalent than cobalt and is detectable in the healthy population. Our aim was to verify if there are any gender- and age-related differences in IMA concentrations and if IMA correlates with cobalt and iron-related proteins. METHODS: IMA, albumin, iron, ferritin, transferrin, and cobalt were measured in 50 men and 50 women divided into two age/fertility-homogeneous groups. RESULTS: Men < 45-years-old showed a statistically significant lower IMA concentration than men ≥ 45 and fertile and menopausal women. Considering all the population studied, IMA does not seem to be correlated with age and is distributed differently by gender; also, Co distribution was different between males and females. CONCLUSIONS: IMA did not correlate with cobalt, iron, ferritin, and transferrin in any group, except for fertile women where IMA presented a statistically significant correlation with serum iron values. Minor expression of IMA in young males together with the results obtained on serum iron in fertile females, could explain the higher accumulation of circulating Co in women compared to men and their different cobalt metabolism.

Release of soluble and vesicular purine nucleoside phosphorylase from rat astrocytes and microglia induced by pro-inflammatory stimulation with extracellular ATP via P2X7 receptors.

Purine nucleoside phosphorylase (PNP), a crucial enzyme in purine metabolism which converts ribonucleosides into purine bases, has mainly been found inside glial cells. Since we recently demonstrated that PNP is released from rat C6 glioma cells, we then wondered whether this occurs in normal brain cells. Using rat primary cultures of microglia, astrocytes and cerebellar granule neurons, we found that in basal condition all these cells constitutively released a metabolically active PNP with Km values very similar to those measured in C6 glioma cells. However, the enzyme expression/release was greater in microglia or astrocytes that in neurons. Moreover, we exposed primary brain cell cultures to pro-inflammatory agents such as lipopolysaccharide (LPS) or ATP alone or in combination. LPS alone caused an increased interleukin-1ß (IL-1ß) secretion mainly from microglia and no modification in the PNP release, even from neurons in which it enhanced cell death. In contrast, ATP administered alone to glial cells at high micromolar concentrations significantly stimulated the release of PNP within 1 h, an effect not modified by LPS presence, whereas IL-1ß secretion was stimulated by ATP only in cells primed for 2 h with LPS. In both cases ATP effect was mediated by P2X7 receptor (P2X7R), since it was mimicked by cell exposure to Bz-ATP, an agonist of P2X7R, and blocked by cell pre-treatment with the P2X7R antagonist A438079. Interestingly, ATP-induced PNP release from glial cells partly occurred through the secretion of lysosomal vesicles in the extracellular medium. Thus, during inflammatory cerebral events PNP secretion promoted by extracellular ATP accumulation might concur to control extracellular purine signals. Further studies could elucidate whether, in these conditions, a consensual activity of enzymes downstream of PNP in the purine metabolic cascade avoids accumulation of extracellular purine bases that might concur to brain injury by unusual formation of reactive oxygen species.

In Vivo Damage of the Head-Neck Junction in Hard-on-Hard Total Hip Replacements: Effect of Femoral Head Size, Metal Combination, and 12/14 Taper Design.

Recently, concerns have been raised about the potential effect of head-neck junction damage products at the local and systemic levels. Factors that may affect this damage process have not been fully established yet. This study investigated the possible correlations among head-neck junction damage level, implant design, material combination, and patient characteristics. Head-neck junctions of 148 retrieved implants were analysed, including both ceramic-on-ceramic (N = 61) and metal-on-metal (N = 87) bearings. In all cases, the male taper was made of titanium alloy. Damage was evaluated using a four-point scoring system based on damage morphology and extension. Patient age at implantation, implantation time, damage risk factor, and serum ion concentration were considered as independent potential predicting variables. The damage risk factor summarises head-neck design characteristics and junction loading condition. Junction damage correlated with both implantation time and damage factor risk when the head was made of ceramic. A poor correlation was found when the head was made of cobalt alloy. The fretting-corrosion phenomenon seemed mainly mechanically regulated, at least when cobalt alloy components were not involved. When a component was made of cobalt alloy, the role of chemical phenomena increased, likely becoming, over implantation time, the damage driving phenomena of highly stressed junctions.

Hypoxia mediates osteocyte ORP150 expression and cell death in vitro.

Skeletal unloading leads to hypoxia in the bone microenvironment, resulting in imbalanced bone remodeling that favors bone resorption. Osteocytes, the mechanosensors of bone, have been demonstrated to orchestrate bone homeostasis. Hypoxic osteocytes either undergo apoptosis or actively stimulate osteoclasts to remove bone matrix during hypoxia. Oxygen­regulated protein 150 (ORP150) is an endoplasmic reticulum­associated chaperone that has been observed to serve an important role in the cellular adaptation to hypoxia and in preventing cellular apoptosis in various tissue types. The current study hypotheses that expression of ORP150 would be increased in osteocytes under hypoxic conditions (1% O2). The MLO­Y4 osteocyte cell line was cultured under normoxic or hypoxic conditions for up to 72 h. It was demonstrated that 1% O2 significantly induced hypoxia after 16 h and up to 72 h, significantly reduced cell number at 8 and 48 h, induced cell death at 8, 24 and 48 h and induced apoptosis at 16, 24 and 48 h. Significant differences in ORP150 mRNA were observed at 72 h, however no differences were observed in the protein expression levels. The relative increase in ORP150 mRNA observed in hypoxia, compared with normoxia, may support its cytoprotective role in oxygen­deprived conditions.

In vivo response of heme-oxygenase-1 to metal ions released from metal-on-metal hip prostheses.

Metal ion release and accumulation is considered to be a factor responsible for the high failure rates of metal-on-metal (MoM) hip implants. Numerous studies have associated the presence of these ions, besides other factors, including a hypoxia­like response and changes in pH due to metal corrosion leading to the induction of the oxidative stress response. The aim of the present study was to verify whether, in patients with a MoM hip prosthesis, mRNA and protein expression of HMOX­1 was modulated by the presence of metal ions and whether patients without prostheses exhibit a different expression pattern of this enzyme. The study was conducted on 22 matched pairs of patients with and without prostheses, for a total of 44 samples. Ion dosage was determined using inductively coupled plasma mass spectrometry equipped with dynamic cell reaction. HMOX­1 gene expression was quantified by reverse transcription-quantitative polymerase chain reaction and HMOX­1 protein expression was analyzed using an enzyme-linked immunosorbent assay. The results demonstrated that although there were significant differences in the metallic ion concentrations amongst the two groups of patients, there was no correlation between circulating levels of cobalt (Co) and chromium (Cr), and HMOX­1 gene and protein expression. Additionally, there was no significant difference in the protein expression levels of HMOX­1 between the two groups. In conclusion, it was demonstrated that circulating Co and Cr ions released by articular prosthetics do not induce an increase in HMOX­1 mRNA and protein expression at least 3.5 years after the implant insertion. The present study suggests that involvement of HMOX­1 may be excluded from future studies and suggests that other antioxidant enzymes, including superoxide dismutase, glutathione peroxidase and reductase should be investigated.

Metal ion release: also a concern for ceramic-on-ceramic couplings?

BIOLOX delta is the newest ceramic composite material of the BIOLOX family and its use in hip devices represents a good alternative to Metal-on-Metal or Metal-on-Polyethylene coupling. Some Metal-on-Metal hip devices have shown chromium and cobalt release, which promoted toxic effects. Furthermore, the ceramic composite contains trivalent chromium, even if strongly bound to the alumina lattice. The present study is aimed at detecting any 'in vivo' release of chromium ions from BIOLOX delta bearings in the blood, erythrocytes and urine of patients. Twenty patients implanted with total hip arthroplasty (THA) with BIOLOX delta-BIOLOX delta couplings and 21 subjects with no implanted prostheses were studied. Inductively coupled plasma mass spectrometry equipped with dynamic reaction cell was used for analysis. In the THA group the Cr ions values were; in blood mean 0.21 µg/l (±0.09), in serum 0.21 µg/l (±0.12), in normalized erythrocytes 0.13 µg/l (±0.09), in normalized urine 0.12 µg/g creatinine (±0.13). In the control group the Cr ions values were; in blood mean 0.22 µg/l (st dev 0.14), in serum 0.17 µg/l (±0.08), in normalized erythrocytes 0.13 µg/l (±0.11), in normalized urine 0.07 µg/g creatinine (±0.08). The Lab reference values were 0.1-5.0 µg/l for blood, 0.1-0.5 µg/l for serum, 0.14-4.58 µg/l for normalised erythrocytes and 0.05-2.2 µg/l for urine. All samples in both groups resulted in chromium levels within the normal reference range and the safety of BIOLOX delta ceramics, in terms of chromium ions release, has been demonstrated.

Essential oils for complementary treatment of surgical patients: state of the art.

Aromatherapy is the controlled use of plant essences for therapeutic purposes. Its applications are numerous (i.e., wellbeing, labour, infections, dementia, and anxiety treatment) but often they have not been scientifically validated. The aim of the present study is to review the available literature to determine if there is evidence for effectiveness of aromatherapy in surgical patients to treat anxiety and insomnia, to control pain and nausea, and to dress wound. Efficacy studies of lavender or orange and peppermint essential oils, to treat anxiety and nausea, respectively, have shown positive results. For other aspects, such as pain control, essential oils therapy has shown uncertain results. Finally, there are encouraging data for the treatment of infections, especially for tea tree oil, although current results are still inconclusive. It should also be considered that although they are, allergic reactions and toxicity can occur after oral ingestion. Therefore, while rigorous studies are being carried out, it is important that the therapeutic use of essential oils be performed in compliance with clinical safety standards.

Detection of cobalt in synovial fluid from metal-on-metal hip prosthesis: correlation with the ion haematic level.

Hip replacement with large metal-on-metal (MoM) coupling has recently been under attention for its metal ions release, inducing several disorders. Since the blood level toxicity threshold for cobalt is known, the aim of this work is to determine whether Co serum and blood levels correlate with the synovial fluid level. Beside this, the synovial fluid Co from patients without prosthesis has also been measured. Co has been determined in 54 samples (32 unilateral MoM and 22 controls) with inductively coupled plasma mass spectrometry in the three matrices. In the prosthesized group, cobalt was significantly higher compared with controls and in the synovial fluid it strongly correlated with whole blood Co (p = 0.847) and serum (p = 0.855). Moreover, the Co levels into whole blood and serum were significantly different. In conclusion, haematic Co concentration correctly reflects Co local level.

An estimation of the number of cells in the human body.

BACKGROUND: All living organisms are made of individual and identifiable cells, whose number, together with their size and type, ultimately defines the structure and functions of an organism. While the total cell number of lower organisms is often known, it has not yet been defined in higher organisms. In particular, the reported total cell number of a human being ranges between 10(12) and 10(16) and it is widely mentioned without a proper reference. AIM: To study and discuss the theoretical issue of the total number of cells that compose the standard human adult organism. SUBJECTS AND METHODS: A systematic calculation of the total cell number of the whole human body and of the single organs was carried out using bibliographical and/or mathematical approaches. RESULTS: A current estimation of human total cell number calculated for a variety of organs and cell types is presented. These partial data correspond to a total number of 3.72 × 10(13). CONCLUSIONS: Knowing the total cell number of the human body as well as of individual organs is important from a cultural, biological, medical and comparative modelling point of view. The presented cell count could be a starting point for a common effort to complete the total calculation.

Uncemented primary total hip arthroplasty, presentation of pain, and expression of osteonectin.

Osteonectin (ON) is an important matrix glycoprotein highly expressed in bone. In several in vitro and animal model studies, ON was used as indicator of the state of osseointegration of implanted devices. There are, however, no studies on ON expression in the synovial fluid of patients with total hip joint replacement (THJR). The purpose of our study was to determine the ON concentration in synovial fluid from three groups of patients: primary uncemented THJR with hip pain ("pain" group; n = 15) and without pain ("no-pain" group; n = 12), and patients with osteoarthitis scheduled to receive a primary THJR (control group; n = 5). For the prosthesized groups, the statistical nature of the correlation between ON concentration and patient age, in situ life of the THJR, presence of periprosthetic osteolysis, and presence of debris in the synovial fluid was individually investigated. ON concentration was determined using enzyme-linked immunosorbent assay, the presence of periprosthetic osteolysis was established using X-radiography and Engh's criteria, and the presence of debris was determined using digestion and EDX spectroscopy. ON concentration was significantly lower in the "pain" group compared with the "no-pain" one (median values 19.0 and 53.2 ng/mL, respectively). ON concentration in the control group (median value: 16.9 ng/mL) was comparable with that reported in the literature. In the prosthesized groups, ON concentration was not correlated with patient age, in situ life of the prosthesis, presence of periprosthetic osteolysis, or presence of debris in the synovial fluid. Our results suggest that cases of unexplained pain in THJR patients could be treated by paying special attention to the osseointegration status of the implant by using ON concentration as an early indicator of this status.

Ceramic debris in hip prosthesis: correlation between synovial fluid and joint capsule.

Detection of ceramic particles in synovial fluids allows early diagnosis of ceramic damage, but there is no evidence of a relationship between ceramic debris in the articular space and in the joint capsule. The aim of the present study is to verify if the particles isolated in the synovial fluid are comparable with those stored in the capsular tissue. Twenty-one patients were enrolled. Both synovial fluid and capsular samples were collected during revision surgery and ceramic particles were isolated and analyzed by scanning electron microscopy and energy-dispersive X-ray microanalysis. It resulted a significant correlation between the samples couples (18 out of 21). This study confirms that the synovial fluid analysis can give a clear definition of the presence of particles in the joint capsule.

Synovial fluid microanalysis allows early diagnosis of ceramic hip prosthesis damage.

The first clinical sign of ceramic hip prosthesis failure is hip noise. We therefore investigated whether isolation, observation at scanning electron microscopy, and chemical identification with microanalysis of particles from synovial fluid of "noisy hip" could be predictive of ceramic damage. Firstly, the level of "physiological wear" of well functioning ceramic-on-ceramic hip prostheses was assessed with this method, then the test was validated as diagnostic method for liner fracture. Twelve asymptomatic patients were enrolled to demonstrate the first aim; 39 cases of noisy hip (GROUP 1), and 7 cases of pending failure not related to ceramic (GROUP 2) were enrolled for the second aim. The analysis of the synovial fluid of the 12 asymptomatic patients allowed to set the "physiological wear" threshold. The analysis of GROUP 1 hips demonstrated the presence of ceramic particles (2 physiological, 12 mild, and 25 strong). The analysis of GROUP 2 showed a physiological presence of ceramic particles in all cases. Revision surgery in GROUP 1 was performed in 16 hips out 25 with strong ceramic particle presence and 2 out of 12 with mild ceramic particle presence. Failure of the ceramic component was evident in all but one of these cases, while the integrity of components was demonstrated in all seven hips of GROUP 2. Synovial fluid microanalysis can be a useful surrogate in predicting ceramic failure particularly when a strong presence of ceramic particles is observed. On the contrary there is not enough evidence to predict ceramic failure in presence of mild positivity.

Monocyte chemoattractant protein 1 expression in synovial fluid of patients with total hip arthroplasty.

Monocyte chemoattractant protein 1 (MCP-1) is a member of the chemokines family that stimulates monocyte chemotaxis and whose expression is induced during osseous inflammation. Total hip arthroplasty (THA) now uses ceramic-on-ceramic (cer-cer) or metal-on-metal (met-met) coupling that is considered the bearing of new generation, with improved performance compared with the previous polyethylene bearings. While the ceramic on ceramic is universally considered highly biocompatible, met-met coupling can induce hypersensitivity correlated to immunological response. This study aimed at quantifying the MCP-1 levels in synovial fluid of THA patients with these two articular couplings; synovial fluid of osteoarthritic patients who underwent primary THA was used as a control. The presence of wear particles originating from the prostheses was also assessed in the synovial fluid by scanning electron microscopy and energy dispersive X-ray spectroscopy. The MCP-1 levels in the synovial fluid of 17 patients with met-met coupling were significantly higher than in 13 patients with cer-cer coupling and in seven controls; median MCP-1 level was 919 pg/mL in the cer-cer group, 4274 pg/mL in the met-met group, and 326 pg/mL in the control group. No correlation was found between MCP-1 levels and the presence of wear particles in the synovial fluid, time from surgery, or periprosthetic osteolysis. We conclude that the presence of the prosthesis is responsible for an increase in the level of MCP-1; moreover, the significantly higher level of this chemokine in met-met coupling can be related to inflammatory and possibly hypersensitivity processes induced by metal ions.

Re-use of explanted osteosynthesis devices: a reliable and inexpensive reprocessing protocol.

INTRODUCTION: Orthopaedic surgical treatments emphasizing immobilization using open reduction and internal fixation with osteosynthesis devices are widely accepted for their efficacy in treating complex fractures and reducing permanent musculoskeletal deformity. However, such treatments are profoundly underutilized in low- and middle-income countries (LMIC), partially due to inadequate availability of the costly osteosynthesis devices. Orthopaedic surgeons in some LMIC regularly re-use osteosynthesis devices in an effort to meet treatment demands, even though such devices typically are regulated for single-use only. The purpose of this study is to report a reprocessing protocol applied to explanted osteosynthesis devices obtained at a leading trauma care hospital. METHODS: Explanted osteosynthesis devices were identified through a Register of Explanted Orthopaedic Prostheses. Guidelines to handle ethical issues were approved by the local Ethical Committee and informed patient consent was obtained at the time of explant surgery. Primary acceptance criteria were established and applied to osteosynthesis devices explanted between 2005 and 2008. A rigorous protocol for conducting decontamination and visual inspection based on specific screening criteria was implemented using simple equipment that is readily available in LMIC. RESULTS: A total of 2050 osteosynthesis devices, including a large variety of plates, screws and staples, were reprocessed using the decontamination and inspection protocols. The acceptance rate was 66%. Estimated labour time and implementation time of the protocol to reprocess a typical osteosynthesis unit (1 plate and 5 screws) was 25 min, with an estimated fixed cost (in Italy) of €10 per unit for implementing the protocol, plus an additional €5 for final sterilization at the end-user hospital site. DISCUSSION: This study was motivated by the treatment demands encountered by orthopaedic surgeons providing medical treatment in several different LMIC and their need for access to basic osteosynthesis devices. The rigorous decontamination protocol and generalized inspection criteria proved useful for efficiently screening a large volume of devices. Given that re-used osteosynthesis devices can yield satisfactory results, this study addresses potential complications of re-used devices and valid concerns that relate to patient safety. Implementing this defined reprocessing protocol into existing re-use practises in LMIC helps to limit the risks of inadequate sterilization and structural failure without adding additional risks to patients receiving re-used devices.

Osteon classification in human fibular shaft by circularly polarized light.

Pattern of osteonal classification referred to collagen fiber orientation in a human fibula was studied. Along the length of the whole bone, serial 100-microm parallel cross sections were obtained and analyzed by circularly polarized light microscopy. The distribution of 3 different kinds of osteons (transversal, alternated and longitudinal-hooped) depending on their collagen fiber orientation were analyzed to determine the effect of length, anatomical quadrant and cortical thickness. Referring to length, the 3 types of osteons appeared with approximately the same relative frequency, but when the symmetry of the fibula was considered and the length was expressed as distance from the bone mid-section, the alternated osteons are predominant in the mid-section. On the contrary, moving toward the epiphyses, the balance is inverted, and transversal together with longitudinal-hooped types become more frequent than the alternated type. Osteonal pattern distribution was not significantly affected by the anatomical quadrant of each section or by the thickness of the cortex. This observation seems to confirm that along the fibula shaft the orientation of collagen fibers within the osteons is consistent with the loading conditions which the bone undergoes.

Assessment of five interleukins in human synovial fluid as possible markers for aseptic loosening of hip arthroplasty.

One of the most important factors that seems to be involved in total hip replacement is periprosthetic osteolysis. As it is well documented that several interleukins (ILs) are triggered in periprosthetic osteolysis, this article investigates the role of five ILs in primary and replacement total hip arthroplasty, understanding if one of them can also predict hip implant loosening, secondary surgery, and prosthesis breakage. The levels of IL-1alpha, 1beta, 6, 8, and 10 in synovial fluid were examined, using a high sensitivity enzyme-linked immunosorbent assay (ELISA) test kit (Pierce Biotechnology, Inc., Rockford, IL, USA) to determine whether these cytokines could be used as markers of enhanced periprosthetic osteolysis, leading to aseptic loosening of total/partial hip arthroplasty or revision surgery. Synovial fluid was harvested from 23 patients undergoing primary total hip arthroplasty and 35 patients undergoing total/partial hip revision due to aseptic loosening. In the revision group, four cases had suffered a prosthesis fracture and five were second revisions. ILs 6 and 8 were significantly higher in the revisions (305 and 817 pg/mL) compared with the primary arthroplasties (151 and 151 pg/mL), including cases with prosthesis fracture and those requiring a second revision. IL-10 levels were lower (not significantly) in second revision samples compared with those of revision samples. IL-1beta levels were significantly higher in prosthesis fracture samples compared with those of all the other revision samples. No statistically significant differences in IL levels were found between osteoarthritis samples and those of other diseases. These results are a step forward to elucidating the complex network of events that are involved in loosening of hip implants.

Pharmacological activation of mGlu2/3 metabotropic glutamate receptors protects retinal neurons against anoxic damage in the goldfish Carassius auratus.

We examined the expression of mGlu2/3 metabotropic glutamate receptors in the retina of the goldfish Carassius auratus. mGlu2/3 receptors were expressed in all retinal layers internal to the photoreceptor layer, particularly in the outer and inner nuclear layers. Although the goldfish brain is able to tolerate prolonged periods of anoxia, we examined whether anoxia could induce retinal damage. Three hours of anoxia induced in the retina the development of apoptotic cell death, as assessed 48 h later by TUNEL staining. TUNEL-positive cells were particularly found in the inner and outer nuclear layers, and were also present in the ganglion cell layer. Pharmacological activation of mGlu2/3 receptors by systemic injection of LY379268 (0.5 mg/kg, i.p., 15 min before the onset of anoxia) substantially protected retinas against anoxia-induced cell death. In contrast, systemic injection of the mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p., 15 min before the onset of anoxia), significantly amplified cell death. Finally, as mGlu2/3 receptors are implicated in the control of extracellular glutamate concentrations, we examined the stimulation of glutamate release in isolated goldfish retinas. Depolarizing medium containing 30 mM KCl led to a significant increase in glutamate release, which was substantially reduced by LY379268. We conclude that activation of mGlu2/3 receptors may provide a major defensive mechanism against ischemic/anoxic retinal damage.

The G51S purine nucleoside phosphorylase polymorphism is associated with cognitive decline in Alzheimer's disease patients.

Alzheimer's disease (AD) is a polygenic and multifactorial complex disease, whose etiopathology is still unclear, however several genetic factors have shown to increase the risk of developing the disease. Purine nucleotides and nucleosides play an important role in the brain. Besides their role in neurotransmission and neuromodulation, they are involved in trophic factor release, apoptosis, and inflammatory responses. These mediators may also have a pivotal role in the control of neurodegenerative processes associated with AD. In this report the distribution of the exonic G/A single nucleotide polymorphism (SNP) in purine nucleoside phosphorylase (PNP) gene, resulting in the amino acid substitution serine to glycine at position 51 (G51S), was investigated in a large population of AD patients (n=321) and non-demented control (n=208). The PNP polymorphism distribution was not different between patients and controls. The polymorphism distribution was also analyzed in AD patients stratified according to differential progressive rate of cognitive decline during a 2-year follow-up. An increased representation of the PNP AA genotype was observed in AD patients with fast cognitive deterioration in comparison with that from patients with slow deterioration rate. Our findings suggest that the G51S PNP polymorphism is associated with a faster rate of cognitive decline in AD patients, highlighting the important role of purine metabolism in the progression of this neurodegenerative disorder.