Gold Injections Research Articles

Employing Electrochemical Potential Cycling to Controlling Surface to Volume Ratio of Nanoporous Gold and Photoelectron Injection into Electrolyte

Nanoporous metals made by alloy corrosion are bicountinuous porous networks that possess nanoscale ligaments and pores and thus a large surface-to-volume ratio. Their ligament and pore size can be tuned between a few nanometers and several microns via thermal annealing [1], which makes them attractive material systems for a variety of applications, including catalysis, sensing, and energy storage. In particular, dealloying-derived nanoporous metals, present novel opportunities for exploring the impact of surfaces on electro-photocatalytic activity of metallic nanostructures [2]. Yet, achieving the ligament and pore sizes in the dealloyed metallic networks below 10 nm, which is especially crucial for understanding an efficient electrochemical charge transfer, is challenging so far.In this study, we demonstrate a successful fabrication of nanoporous gold (npAu) thin films via electrochemical dealloying with the ligament size down below 10 nm on quartz substrate. We study the material by means of in situ photoelectrochemical setup while simultaneously varying the electrode potential in 0.5 M H2SO4 electrolyte. To probe the size effect on the photocurrent response, we exploit cyclic voltammetry (CV) in order to promote coarsening of the ligaments of npAu networks. By varying a number of CV cycles, we were able to induce subtle changes in the ligament size, therefore modifying the surface-to-volume ratio of the nanoporous metals at the lower limit of the nanoscale.Our results show that this approach provides an excellent foundation for future optical investigations of surface effects on the internal quantum efficiency of high-surface area metallic photoelectrodes.Our study demonstrates that modifying the surface-to-volume ratio of the sample by electrochemistry allows us to control the hot electron generation and injection processes in nanoscale plasmonic systems. Moreover, the internal quantum efficiency of the npAu network photoelectrode is significantly influenced by the size of its ligaments. In contrast to prior findings that suggested efficiency would level off with decreasing ligament size [3], we have observed a continuous nonlinear increase in quantum efficiency as the ligament size decreased from 16 to 8 nm. This result is attributed to the increase in absorption by the electrons colliding with the surface (Landau damping) and increase of emission of this electrons into the electrolyte due to possibility of multiple collisions with the surface.

Gold nanoparticle intratesticular injections as a potential animal sterilization tool: Long-term reproductive and toxicological implications

This study aimed to evaluate the gold nanoparticles (AuNPs) animal sterilizing potential after intratesticular injections and long-term adverse reproductive and systemic effects. Adult male Wistar rats were divided into control and gold nanoparticle (AuNPs) groups. The rats received 200 µL of saline or AuNPs solution (16 µg/mL) on experimental days 1 and 7 (ED1 and ED7). After 150 days, the testicular blood flow was measured, and the rats were mated with females. After mating, male animals were euthanized for histological, cellular, and molecular evaluations. The female fertility indices and fetal development were also recorded. The results indicated increased blood flow in the testes of treated animals. Testes from treated rats had histological abnormalities, shorter seminiferous epithelia, and oxidative stress. Although the sperm concentration was lower in the AuNP-treated rats, there were no alterations in sperm morphology. Animals exposed to AuNPs had decreased male fertility indices, and their offspring had lighter and less efficient placentas. Additionally, the anogenital distance was longer in female fetuses. There were no changes in the histology of the kidney and liver, the lipid profile, and the serum levels of LH, testosterone, AST, ALT, ALP, albumin, and creatinine. The primary systemic effect was an increase in MDA levels in the liver and kidney, with only the liver experiencing an increase in CAT activity. In conclusion, AuNPs have a long-term impact on reproduction with very slight alterations in animal health. The development of reproductive biotechnologies that eliminate germ cells or treat local cancers can benefit from using AuNPs.

Rheuminations

I’ll be honest…it has been 35+ years since I started Medical School [MBBS]. And in the realm of Medicine at large, and Immunology/Rheumatology in specific, we are still struggling to find a ‘cure’ for chronic systemic inflammatory immune-mediated diseases also known as ‘autoimmune rheumatic diseases (ARD)’. Rheumatology is still in its cradle having gotten the recognition as a subspecialty of Medicine only in 1972. I have seen the field evolve in terms of understanding the orchestrated ‘play’ of the immune cells along with cytokines etc. over the past 3 decades, all of which has led to the concept and birth of ‘biologic’ disease modifying anti-rheumatic drugs [b-DMARDs]. The first b-DMARD to get approved by the Food and Drugs Administration [FDA] was etanercept, a TNF-alpha receptor fusion protein in 1998. Infliximab, a chimeric monoclonal antibody against TNF soon followed in 1999. Ever since then, there has been a flurry of b-DMARDs including 3 more in the same family of TNF-antagonists, 2 in the Interleukin [IL]-6 antagonist class, 1 blocker of the second co-stimulatory T-cell signaling: CTLA-4Ig, 3 IL-1 antagonists, B-cell depleting chimeric monoclonal antibody directed against CD-20 etc. Also, 3 oral Janus-kinase inhibitors have joined the ‘gang’ and are called targeted synthetic DMARDs. I still remember the pre-b-DMARD era when rip roaring rheumatoid arthritis was still around, and with my Ustaad Saheb (Mentor), all what we had to offer pharmaceutically were the conventional synthetic [cs] DMARDs including methotrexate, hydroxychloroquine, sulfasalazine, leflunomide and [the younger generation can hold their breath] cyclosporine, d-penicillamine, chlorambucil…GOLD injections and even cyclophosphamide! Corticosteroids have been around since 1950! The 1st and “so far” […well, I/You might be next one!] the only Nobel Prize winning revelation in the realm of Rheumatology......................................

Numerical investigation of the effect of vessel size and distance on the cryosurgery of an adjacent tumor

Cryosurgery is an efficient cancer treatment which can be used for non-invasive ablation of some internal tumors such as liver and prostate. Tumors are usually located near the large blood vessels and the heat convection may affect the progression of the ice ball. Hence it is necessary to predict the surgery procedure and its consequences earlier. In spite of the recent studies it is still unclear that which arteries will significantly affect the freezing treatment of tumors and which can be ignored. Therefore a numerical model of a spherical 3 cm diameter liver tumor, subjected to cryosurgery was developed. The specific thermophysical properties were applied to the tumor and healthy tissues in frozen and unfrozen states. A simplified Hepatic artery with different anatomical diameters was placed in different positions relative to the tumor and energy and momentum equations were solved. The temperature distribution and the shape of the resultant ice ball were discussed. The results showed that a 4 mm diameter artery in the vicinity of a tumor will increase the minimum temperature achieved at the tumor boundary by 12.5 °C and therefore significantly affects the cryosurgery outcome. This may cause insufficient freezing which leads to incomplete death of tumor cells, failure of the surgery and tumor regenesis. Eventually it was shown that injection of gold and Fe3O4 nanoparticles to the surrounding tissue of the artery can enhance the heat transfer and progression of the ice ball, making temperature distribution similar to the no vessel state. Development of computational models can provide the physicians an applicable tool which helps them recognize how efficient a treatment method will be for a specific case and design a suitable cryosurgery plan.

Blood Biochemical and Hematological Study after Subacute Intravenous Injection of Gold and Silver Nanoparticles and Coadministered Gold and Silver Nanoparticles of Similar Sizes.

Background To investigate the effect of subacute intravenous administration AgNP (silver nanoparticles, 10 nm) and AuNP (gold nanoparticles, 12.8 nm) and AgNP/AuNP mixture to blood biochemistry, hematology, and platelet coagulation, subacute toxicity study was conducted. Methods AuNP and AgNP in which their size distribution was not statistically different, mixed or separate, were injected into the caudal vein of male Sprague-Dawley rats for 4 weeks. The rats were allowed to recover for a further 4 weeks in order to examine systemic toxicity expressed in the blood biochemistry and hematology. The dose groups (5 males per group for the administration and 3 males for the recovery) consisted of 7 divisions, i.e., control, AgNP (with a low dose of 10 μg/kg/day and a high dose of 100 μg/kg/day), AuNP (with a low dose of 10 μg/kg/day and a high dose of 100 μg/kg/day), and mixed AgNP/AuNP (with a low dose of 10/10 μg/kg/day and a high dose of 100/100 μg/kg/day). Results There were no significant dose-related changes in the hematology and blood biochemical values for the rats. Coagulation time in terms of the active partial thromboplastin time (APTT) and prothrombin time (PT) did not show any significant changes, when compared to the control group. Conclusion The subacute injection of AuNP and AgNP or their mixture did not induce any noticeable systemic toxicity.

Microfluidic Assisted Synthesis of Hybrid Au–Pd Dumbbell-like Nanostructures: Sequential Addition of Reagents and Ultrasonic Radiation

A sequential-addition microfluidic reactor and an ultrasonic integrated microfluidic reactor were designed to produce with high selectivity hybrid Au–Pd dumbbell-like nanostructures (Au–Pd DBNPs), consisting of a palladium segment tipped with gold heads. A single-stage synthesis was not able to synthesize hybrid nanostructures due to the high reactivity of gold. On the other hand, a two-step method was successful by first synthesizing Pd nanorod-like structures and subsequent growing of Au on the tips of those structures by the localized galvanic replacement reaction. The localized deposition of Au onto both tips of palladium rods was achieved by using two different microfluidic approaches: (i) by sequential injection of gold along the reaction channel at 100 °C and a 5 min residence time, and (ii) by ultrasonic radiation at room temperature and a 2 min residence time. The synthesized Au–Pd DBNPs had higher electrocatalytic activity in the ethanol oxidation reaction in alkaline media than the Pd nanorods.

Kisspeptin-mediated regulation of testicular activity of rats under the effect of gold nanoparticles

There are a variety of biomedical applications of nanoparticles. They can be used as drug carriers, anti-tumor agents, biosensors and modulators of immune response. But full-scale real clinical application of nanomaterials requires a great deal of information on their safety and biotoxicity. Even traditionally harmless materials, like gold, can obtain toxic features when scaled to the nanosize. In vitro studies showed that nanoparticles can be geno- and cytotoxic, but their effects on the body as a whole remain largely a mystery. To shed some light on this, our study focused on the reproductive toxicity of nanomaterials. We synthesized 10–15 nm gold nanoparticles through the reduction of sodium tetrachloroaurate (III) in an alkaline medium with the addition of sodium polyphosphate as a stabilizing agent. Next, these particles were administered intraperitoneally to young and old rats for 10 days. To test functional capabilities of the testes, we injected kisspeptin-10 or its antagonist peptide-234 intracerebroventricularly. These substances are known to stimulate or inhibit the central component of the hypothalamic-pituitary-gonadal axis respectively. After the routine histological procedures, we measured the diameter of seminiferous tubules and the nuclear cross-sectional area of Sertoli cells as markers of testicular spermatogenic activity and a cross-sectional area of the Leydig cells’ nuclei as a marker of testicular steroidogenesis. We found that injections of nanogold caused no significant changes in the young animals. At the same time, morphometric parameters of adult animals were significantly lower compared to control, although we observed no pathological changes in the tissue. Combined administration of gold nanoparticles and kisspeptin showed that the stimulatory effect of the latter was not observed at all. This is a specific feature of toxicants called “endocrine disruptors”. Moreover, we found morphological signs of testicular degeneration, which are characteristic of the low-testosterone state. Simultaneous injections of gold and peptide-234 resulted in the highest degree of testicular functional downregulation, regardless of age. Taken as a whole, our data indicates that gold nanoparticles disrupt the regulatory network of the hypothalamic-pituitary-gonadal axis, possibly due to direct action on the interstitial cells and spermatogenic epithelium.

E62 An Audit of the Use of the Intramuscular Myocrisin (Gold) Injections in the Rheumatology Department

E62 An Audit of the Use of the Intramuscular Myocrisin (Gold) Injections in the Rheumatology Department

Fully Parallel Electrical Impedance Tomography Using Code Division Multiplexing.

Electrical Impedance Tomography (EIT) has been dominated by the use of Time Division Multiplexing (TDM) and Frequency Division Multiplexing (FDM) as methods of achieving orthogonal injection of excitation signals. Code Division Multiplexing (CDM), presented in this paper is an alternative that eliminates temporal data inconsistencies of TDM for fast changing systems. Furthermore, this approach eliminates data inconsistencies that arise in FDM when frequency bands of current injecting electrodes are chosen over frequencies that have large changes in the imaged object's impedance. To the authors knowledge no fully functional wideband system or simulation platform using simultaneous injection of Gold codes currents has been reported. In this paper, we formulate, simulate and develop a fully functional pseudo-random (Gold) code driven EIT system with 15 excitation currents and 16 separate voltage measurement electrodes. In the work we verify the use of CDM as a multiplexing modality in simultaneous injection EIT, using a prototype system with an overall bandwidth of 15 kHz, and attainable speed of 462 frames/s using codes with a period of 31 chips. Simulations and experiments are performed using the Electrical Impedance and Diffuse Optics Reconstruction Software (EIDORS). We also propose the use of image processing on reconstructed images to establish their quality quantitatively without access to raw reconstruction data. The results of this study show that CDM can be successfully used in EIT, and gives results of similar visual quality to TDM and FDM. Achieved performance shows average position error of 3.5% and size error of 6.2%.

Some inferences from in vivo experiments with metal and metal oxide nanoparticles: the pulmonary phagocytosis response, subchronic systemic toxicity and genotoxicity, regulatory proposals, searching for bioprotectors (a self-overview).

The purpose of this paper is to overview and summarize previously published results of our experiments on white rats exposed to either a single intratracheal instillation or repeated intraperitoneal injections of silver, gold, iron oxide, copper oxide, nickel oxide, and manganese oxide nanoparticles (NPs) in stable water suspensions without any chemical additives. Based on these results and some corroborating data of other researchers we maintain that these NPs are much more noxious on both cellular and systemic levels as compared with their 1 μm or even submicron counterparts. However, within the nanometer range the dependence of systemic toxicity on particle size is intricate and non-unique due to complex and often contra-directional relationships between the intrinsic biological aggressiveness of the specific NPs, on the one hand, and complex mechanisms that control their biokinetics, on the other. Our data testify to the high activity of the pulmonary phagocytosis of NPs deposited in airways. This fact suggests that safe levels of exposure to airborne NPs are possible in principle. However, there are no reliable foundations for establishing different permissible exposure levels for particles of different size within the nanometric range. For workroom air, such permissible exposure levels of metallic NP can be proposed at this stage, even if tentatively, based on a sufficiently conservative approach of decreasing approximately tenfold the exposure limits officially established for respective micro-scale industrial aerosols. It was shown that against the background of adequately composed combinations of some bioactive agents (comprising pectin, multivitamin-multimineral preparations, some amino acids, and omega-3 polyunsaturated fatty acid) the systemic toxicity and even genotoxicity of metallic NPs could be markedly attenuated. Therefore we believe that, along with decreasing NP-exposures, enhancing organisms’ resistance to their adverse action with the help of such bioprotectors can prove an efficient auxiliary tool of health risk management in occupations connected with them.

Injection of ligand-free gold and silver nanoparticles into murine embryos does not impact pre-implantation development.

Intended exposure to gold and silver nanoparticles has increased exponentially over the last decade and will continue to rise due to their use in biomedical applications. In particular, reprotoxicological aspects of these particles still need to be addressed so that the potential impacts of this development on human health can be reliably estimated. Therefore, in this study the toxicity of gold and silver nanoparticles on mammalian preimplantation development was assessed by injecting nanoparticles into one blastomere of murine 2 cell-embryos, while the sister blastomere served as an internal control. After treatment, embryos were cultured and embryo development up to the blastocyst stage was assessed. Development rates did not differ between microinjected and control groups (gold nanoparticles: 67.3%, silver nanoparticles: 61.5%, sham: 66.2%, handling control: 79.4%). Real-time PCR analysis of six developmentally important genes (BAX, BCL2L2, TP53, OCT4, NANOG, DNMT3A) did not reveal an influence on gene expression in blastocysts. Contrary to silver nanoparticles, exposure to comparable Ag+-ion concentrations resulted in an immediate arrest of embryo development. In conclusion, the results do not indicate any detrimental effect of colloidal gold or silver nanoparticles on the development of murine embryos.

Metallic gold beads in hyaluronic acid: a novel form of gold-based immunosuppression? Investigations of the immunosuppressive effects of metallic gold on cultured J774 macrophages and on neuronal gene expression in experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is a neurodegenerative disease caused by recurring attacks of neuroinflammation leading to neuronal death. Immune-suppressing gold salts are used for treating connective tissue diseases; however, side effects occur from systemic spread of gold ions. This is limited by exploiting macrophage-induced liberation of gold ions (dissolucytosis) from gold surfaces. Injecting gold beads in hyaluronic acid (HA) as a vehicle into the cavities of the brain can delay clinical signs of disease progression in the MS model, experimental autoimmune encephalitis (EAE). This study investigates the anti-inflammatory properties of metallic gold/HA on the gene expression of tumor necrosis factor (Tnf-α), Interleukin (Il)-1β, Il-6, Il-10, Colony-stimulating factor (Csf)-v2, Metallothionein (Mt)-1/2, Bcl-2 associated X protein (Bax) and B cell lymphoma (Bcl)-2 in cultured J774 macrophages and in rodents with early stages of EAE. Cells grew for 5 days on gold/HA or HA, then receiving 1,000 ng/mL lipopolysaccharide (LPS) as inflammatory challenge. In the EAE experiment, 12 Lewis rats received gold injections and control groups included 11 untreated and 12 HA-treated EAE rats and five healthy animals. The experiment terminated day 9 when the first ten animals showed signs of EAE, only one of which were gold-treated (1p = 0.0367). Gene expression in the macrophages showed a statistically significant decrease in Il-6, Il-1β and Il-10-response to LPS; interestingly HA induced a statistically significant increase of Il-10. In the EAE model gene expression of inflammatory cytokines increased markedly. Compared to EAE controls levels of Tnf-α, Il-1β, Il-10, Il-6, IL-2, Ifn-γ, Il-17, transforming growth factor (Tgf)-β, superoxide dismutase (Sod)-2, Mt-2 and fibroblast growth factor (Fgf)-2 were lower in the gold-treated group. HA-treated animals expressed similar or intermediate levels. Omnibus testing for reduced inflammatory response following gold-treatment was not significant, but tendencies towards a decrease in the Sod-2, Fgf-2, Il-1β response and a higher Bdnf and IL-23 gene expression were seen. In conclusion, our findings support that bio-liberation of gold from metallic gold surfaces have anti-inflammatory properties similar to classic gold compounds, warranting further studies into the pharmacological potential of this novel gold-treatment and the possible synergistic effects of hyaluronic acid.

Osteolysis of the hips in a patient with long term rheumatoid arthritis

Case presentation: A fifty four year old African American female with history of rheumatoid arthritis (RA) presented to the emergency room with signs and symptoms of community acquired pneumonia. Patient was diagnosed with RA 30 years ago and was treated initially with non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and gold injections for 3 months since then she didn't receive any disease modifying anti rheumatic drugs (DMARD) or corticosteroids. On examination, she was wheelchair bound with multiple joint deformities: ulnar deviation, swan neck deformities, without any signs of active synovitis. Rheumatoid nodules were absent. She had severe limitation of passive and active movement of the hip joints bilaterally. Images of the pelvis showed resporption of the femoral (1). Marked subchondral sclerosis was noted in the acetabulum. CT scan of the pelvis was done to rule out subcapital femoral neck fracture. It demonstrated advanced degenerative changes in both hip joints with partial resorption of both femoral heads worse on the left, no fracture was noted. Conclusion: Osteolysis is a complication of long term untreated RA that is rarely seen in adults with RA and is more common in JRA.

Hybrid polarity and carrier injection of gold and gadolinium oxide bi-nanocrystals structure

In this study, the carrier injection mechanism of gold and gadolinium oxide bi-nanocrystals (BNCs) with hafnium dioxide NC separation layer was investigated. Further, an N-shaped carrier injection curve was observed under positive gate bias. It is resulted from the hybrid polarity and carrier injection. To identify the injection, the activation energies of charge loss were analyzed, and it was found that the substrate-injected electrons and gate-injected holes were stored in the BNCs. The gate-injected carriers were trapped at the Au-NCs and HfO2 interface, exhibiting high-density (>2.45 × 1012 cm−2) and high-speed (∼μs) operation characteristics suitable for future use in flash memories.

Adjuvant properties of gold nanoparticles

This review summarizes known data and the results of our own investigations into the application of gold nanoparticles as an antigen (AG) carrier and as an adjuvant in immunization in the in vivo preparation of antibodies (ABs). We have developed a technology for the production of ABs against various AGs by using colloidal gold as a carrier and as an adjuvant. The repeated injection of colloidal gold (CG)-AG conjugates (with or without the use of Freund’s complete adjuvant) into animals yielded specific high-titer ABs for a variety of AGs with no concomitant ABs. Gold nanoparticles used as an AG carrier activated the phagocytic activity of macrophages and influenced the functioning of lymphocytes, which apparently may be responsible for their immunomodulating effect. Thus, gold nanoparticles can facilitate the synthesis of ABs in rabbits, rats, and mice, in particular, by reducing the amount of required AG when compared to immunization using Freund’s complete adjuvant.

Direct observation of localized conduction pathways in photocross-linkable polymer memory

Resistive switching in photocross-linkable polymer memory devices was found to occur in localized areas of the device. In order to elucidate the reason behind the switching, we used focused ion-beam to prepare a cross-section of the device. It was found that after the device was switched to the high conductive state, in certain parts of the device, the electrodes were only about 5 nm apart. This was probably caused by a combination of high electric field and metal injection into the polymer film. Gold injection into the polymer film by locally enhanced electric field was confirmed by transmission electron microscope-energy dispersive x-ray analysis. This model was in agreement with both the temperature dependent and transient behavior of our device. We conclude that the non-uniformities at the nanoscale interface of the electrode dominated the device characteristics while the polymer played only a secondary role.

Practice Spotlight: Marie Craig and The Arthritis Program (TAP) at Southlake Regional Health Centre

Care for patients with arthritis has improved greatly over the past 20 years. As a pharmacist working in rheumatology, Marie Craig (known previously as Marie Chambers) has been an active participant in this evolution. Joining the rheumatology team at Southlake Regional Health Centre, Newmarket, Ontario, in 1986, she has made the transition from educating patients about gold injections in the 1980s to educating them about self-injection of methotrexate in the 1990s and the use of biologics in the new millennium. Ms Craig started her career in arthritis care after 16 years at St Michael’s Hospital in Toronto. Joining the Pharmacy Department of Southlake Regional Health Centre in 1986, she soon became involved with the rheumatology team. In 1991, Southlake received funding from the Ontario Ministry of Health and Long-Term Care to establish a rheumatology outpatient program, officially known as The Arthritis Program or TAP. Through this funding Ms Craig formally joined The Arthritis Program, where her new colleagues became the program’s coordinator, 2 occupational therapists, 2 physical therapists, a social worker, and 2 rheumatologists. TAP, which provides care for patients with 135 types of arthritis, not only services the York Region but also draws 2000 new patient referrals per year from a much larger geographic area. The TAP pharmacist’s practice is integrated with the program’s vision of central coordination of all health care disciplines during any patient’s visit. This centralization of care includes documenting the activities of all disciplines in a single health care record, which contributes to more comprehensive care and reduces duplication of not only charting but also patient visits. The one-site, one-chart (including rheumatologists’ notes and health professionals’ charting) vision eliminates the need for each discipline to ask the same questions, while offering the patient easy and continuous access to integrated care. Guided by the Registered Health Professions Act, each health care professional is educated experientially in rheumatology and encouraged to fine-tune his or her discipline-specific skills while thinking “outside the box”. Working together at one site in the Tannery Mall in Newmarket, TAP staff members offer arthritis assessment, education, and treatment by individual appointment, group sessions (for inflammatory arthritis, osteoarthritis, fibromyalgia, and osteoporosis), Rheumatology Clinic appointments (with urgent access to the rheumatologist and other members of the team), and telephone consultation. Through interactions with patients, the TAP pharmacist and other team members frequently identify medication issues requiring intervention. The TAP pharmacist intervenes on behalf of the patient either through the Rheumatology Clinic or through an individual appointment for medication review and education. A large component of the TAP pharmacist’s practice involves assessing medication tolerance and ensuring appropriate education to prepare patients to self-manage their disease. This work environment and role allowed Ms Craig to practise according to the philosophy of pharmaceutical care, even before this philosophy had been firmly defined or taught. After 20 years of exposure to patient medication concerns, Ms Craig developed a medication decision model that asks patients to balance the probable side effects of the arthritis (if untreated) against the benefit of the medication and its possible side effects. The medication information is presented to the patient in an unbiased manner, with the ultimate understanding that it is the patient who will make an informed decision about his or her care. At times, the TAP pharmacist acts as a mediator, advocating on behalf of both the patient and the rheumatologist to find a medication management strategy agreeable to both. Ms Craig and the TAP team document clinical activities in the patient chart and track workload statistics for the

Rheumatology 50 years ago: a short personal history

AbstractThis report reviews attitudes to the rheumatic diseases and treatment methods in use some 50 years ago. The focus is on Professor J. H. Kellgren's unit at the Manchester Royal Infirmary in the UK. For rheumatoid arthritis, aspirin, phenylbutazone, gold injections, antimalarials and prednisolone were all available and bed rest was probably overused. The Charnley hip replacement arthroplasty was being trialed but in 1960 had not been perfected. Kellgren and the two other great UK figures in rheumatology at the time, E. G. L. Bywaters and J. J. R. Duthie appeared to me to have only a limited interest in immunology, apart from the role of rheumatoid factor in rheumatoid arthritis and related conditions. Concentration remained to some extent on proteoglycans and collagen as befitting the 1950s concept of ‘collagen diseases’.

The Anti-rheumatic Gold Salt Aurothiomalate Suppresses Interleukin-1β-induced Hyaluronan Accumulation by Blocking HAS1 Transcription and by Acting as a COX-2 Transcriptional Repressor

Gold compounds are among the oldest disease-modifying drugs and are still widely used today for treating rheumatoid arthritis. Despite decades of use, little is known about the mode of action of this class of drugs. Here we have demonstrated that aurothiomalate (AuTM) suppresses hyaluronan accumulation by blocking interleukin (IL)-1beta-induced hyaluronan synthase-1 transcription. We have further demonstrated that, in fibroblast-like synoviocytes (FLSs), AuTM acts as a specific COX-2 transcriptional repressor in that IL-1beta-induced COX-2 transcription is blocked, whereas COX-1 transcription and translation is unaffected. As a consequence, PGE2 levels released by FLS are dose-dependently reduced in cells exposed to AuTM. Of similar importance is the demonstration that AuTM does block NFkappaB-DNA interaction. In addition, two other transcription factors implicated in inflammatory events, namely AP-1 and STAT3, are blocked as well. The effect on NFkappaB likely explains the inhibition of COX-2 as well as that of HAS1, as both are genes that depend on the activation of NFkappaB. Interestingly, AuTM does not interfere with IL-1beta-induced IkappaB alpha degradation, in most cases a prerequisite for subsequent NFkappaB activation. Furthermore, evidence is presented that, in FLS, AuTM blocks NFkappaB-DNA interaction neither by binding to NFkappaB binding sites nor by interacting with activated NFkappaB proteins. Taken together, AuTM treatment of FLS blocks two of the most important proinflammatory events that are associated with rheumatoid arthritis. AuTM blocks the release of PGE2 and prevents the activation of NFkappaB, therefore blocking IL-1beta-induced hyaluronan accumulation and likely a series of other pro-inflammatory NFkappaB-dependent genes.

Preliminary study of the lymphatic drainage system of the nose and paranasal sinuses and its role in detection of sentinel metastatic nodes

ConclusionsThe normal nasal lymphatic drainage runs via the facial vessels into the neck lymphatic nodes of levels I–II and this drainage pattern was found in our patients with sinonasal tumors. We found only one true-positive sentinel lymph node (SLN). Our pathological material was very limited and so further investigations are required before any valid conclusions can be drawn concerning the clinical value of SLNs in nasal tumors.ObjectivesTo detect the lymph collection route of the nasal fossae and paranasal sinuses and to identify the first echelon in the tumor metastatic cascade in order to prevent the risk of occult metastases in N0 necks in patients with primary head and neck squamous cell carcinoma (SCC).Material and methodsOur control group comprised 30 patients (20 females; age range 19–50 years) suffering from chronic otitis media who had an anatomically normal nose and a cNO neck on palpation. The pathological group comprised 6 patients (2 females; age range 40–85 years) suffering from sinonasal tumors: 3 SCC, 1 recurrent melanoma, 1 ameloblastoma and 1 inverted papilloma. All had a clinically staged cNO neck on palpation and CT. In the control group, lymphoscintigraphy was carried out by means of unilateral injection of radioactive gold into the head of the inferior turbinate. The tracer was identified using a gamma camera 3 and 6 h after the injection. In the pathological group the chosen tracer was technetium, which was administered 1 day prior to surgery by means of injections into the heads of the inferior and middle turbinates, into the nasal septum and into the retromaxillary gingival mucosa. The tracer was identified transcutaneously using a navigator probe in the gamma camera at 15 min, 30 min and 1 h post-injection. A mark was drawn on the skin corresponding to the hot spot of the SLN. The study was repeated 30 min before surgery. The neck incision was selected according to the location of the SLN. A hand-held gamma probe was used in the operating theatre to detect in situ the radioactivity of the surgical excisional nasal area and the cervical SLN. Once the SLN was excised its radioactivity was confirmed ex situ, taking into account that the activity counts were at least three times greater than background. Postoperatively, all SLNs were histopathologically examined and cytokeratin staining was carried out immunohistochemically using the monoclonal antibody cocktail AE1/AE3.ResultsIn the control group, intense activity at the injection tracer site and lower activity in the submandibular area (level I) were detected in 26.6% of cases. Nasal radioactivity persisted for 6 h post-injection and submandibular radioactivity increased, also reaching the area corresponding to neck node level II (70%). In two cases (6.6%), radioactivity was observed in the retropharyngeal nodes. In the pathological group, the SLN was found in the submandibular area (level I) in three cases, and in the ameloblastoma patient three SLNs were found at levels I–II. Three cases were false positives, and no metastases were detected using any of the histopathological procedures. The only one true positive corresponded to a female with an SCC of the maxillary infrastructure with invasion of the gingival mucosa. The histopathological code was 1 and a metastasis was detected on hematoxylin–eosin examination. In the other two cases no SLNs were detected.