Evaluation of metalloproteinases-2, -9, and -13 post photobiomodulation in mice talocrural joint.

The extracellular matrix (ECM) is the main constituent of connective tissue with structural and regulatory functions, stimulating cell differentiation and proliferation. Moreover, ECM is a dynamic structure in the constant remodeling process, which is controlled by a balance between metalloproteinases (MMPs) and their inhibitors (TIMPs). Photobiomodulation (PBM) is widely described in the literature and applied in clinical practices, although its effects on ECM have not yet been elucidated. Therefore, it was evaluated if PBM could alter ECM components, such as MMP-2, -9, -13, and TIMP-2 from mice talocrural joints. Mice were divided into 3 groups (n = 6): control, PBM 3 J cm-2, and PBM 30 J cm-2. A low-level laser (830 nm, 10 mW, 0.05 irradiated area, energy densities 3 J cm-2 and 30 J cm-2, the irradiation time of 15 and 150 s, respectively, continuous wave) was applied on the joint for 4 consecutive days. mRNA levels of metalloproteinases genes (MMP-2, MMP-9, and MMP-13), their regulator (TIMP-2), and protein expressions of MMP-13 and TIMP-2 were quantified. PBM can alter only mRNA relative levels of MMP-2 at 30 J cm-2 (p < 0.05), while MMP-9, MMP-13, and TIMP-2 mRNA relative levels did not demonstrate statistical differences for any of the groups (p > 0.05). Regarding protein expressions, MMP-13 demonstrated positive-labeled cells, only in articular cartilage, although the cell quantification did not demonstrate statistical differences when compared with the control group (p > 0.05). TIMP-2 did not present positive-labeled cells for any tissues evaluated. Our results indicate that PBM can alter MMP-2 mRNA relative level but cannot alter MMP-9, MMP-13, and TIMP mRNA relative levels. Moreover, both MMP-13 and TIMP-2 proteins were also unaltered after PBM.

Re-irradiation for osteoarthritis-retrospective analysis of 217 joints.

PURPOSE: Osteoarthritis is a common disease with a prevalence of approximately 8.9% among the average population. One treatment option is low-dose radiotherapy. Some authors mention that they apply a second or third course of radiation for recurrent pain or partial or no response to the initial course. As the results of re-irradiation have not been analysed systematically, the aim of this study was to document the results of repeated radiation treatment and to identify those patients who will benefit. METHODS AND MATERIALS: The analysis was performed on patients of three German radiotherapy institutions and included 217 re-irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy as well as at the follow-up of 24 months. The median age of the patients was 67 years, with 40% male and 60% female patients. Re-irradiation was indicated because the initial radiotherapy resulted in no response in 21.2%, in partial response in 41.5%, and in recurrent pain in 37.3%. RESULTS: We found a significant response to re-irradiation. For the whole sample, the median pain was 6 before re-irradiation, 4 after 6 weeks, and 3 after 12 weeks, 6 months, 12 months, and 24 months. The percentage of patients being free of pain or with very little pain was approximately 25% 12 months after re-irradiation. All subgroups, notably those with no response to the first course versus partial response to the first course versus recurrent pain, had significant reduction of pain. CONCLUSION: Re-irradiation of osteoarthritis is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months.

Low-Dose Radiotherapy Has No Harmful Effects on Key Cells of Healthy Non-Inflamed Joints.

Low-dose radiotherapy (LD-RT) for benign inflammatory and/or bone destructive diseases has been used long. Therefore, mechanistic investigations on cells being present in joints are mostly made in an inflammatory setting. This raises the question whether similar effects of LD-RT are also seen in healthy tissue and thus might cause possible harmful effects. We performed examinations on the functionality and phenotype of key cells within the joint, namely on fibroblast-like synoviocytes (FLS), osteoclasts and osteoblasts, as well as on immune cells. Low doses of ionizing radiation showed only a minor impact on cytokine release by healthy FLS as well as on molecules involved in cartilage and bone destruction and had no significant impact on cell death and migration properties. The bone resorbing abilities of healthy osteoclasts was slightly reduced following LD-RT and a positive impact on bone formation of healthy osteoblasts was observed after in particular exposure to 0.5 Gray (Gy). Cell death rates of bone-marrow cells were only marginally increased and immune cell composition of the bone marrow showed a slight shift from CD8⁺ to CD4⁺ T cell subsets. Taken together, our results indicate that LD-RT with particularly a single dose of 0.5 Gy has no harmful effects on cells of healthy joints.

The long-term effects of radioactive phosphorous synoviorthesis on hemophilic arthropathy.

BACKGROUND: Radioactive synoviorthesis was carried out by an injection of radioactive materials into the joint that has been known as a successful alternative treatment to invasive surgical synovectomy. This study was designed to evaluate short-term and long-term results and complications of radioactive synovectomy of hemophilic arthropathy using radioactive phosphorus. MATERIALS AND METHODS: This study was conducted on 40 patients with hemophilic arthropathy. After obtaining clotting factors, the intra-articular injections of radioactive phosphorus were done. Thirteen patients were evaluated during 36 months (short-term follow-up) and 27 patients were followed up for more than 36 months (long-term follow-up). Patients were evaluated for hemarthrosis, factor consumption per month, joint range of motion (ROM) and clinical and radiological involvement grade. RESULTS: The patients mean age was 22.9 ± 6.6 and there were 38 men and 2 women. Consumption of clotting factors was significantly reduced in the short-term follow-up of patients (p < 0.05), but there was no significant difference in the long-term follow-up (p > 0.05). ROM decreased significantly in the long-term follow-up (p < 0.05). Radiologic evaluation showed significantly increased involvement in their joints (p < 0.05). CONCLUSION: Using radioactive synoviorthesis led in decreased consumption of clotting factors and the hemarthrosis incidence in short term but it did not have significant impact on clinical situation (ROM) and radiological findings of hemophilic patients in long-term follow-up.

A single muscle moves a crustacean limb joint rhythmically by acting against a spring containing resilin.

BACKGROUND: The beating or fanning movements of three pairs of maxilliped flagella in crabs and crayfish modify exhalent gill currents while drawing water over chemoreceptors on the head. They play an integral part both in signalling by distributing urine odours, and in active chemosensation. RESULTS: The rhythmical maxilliped movements start with maxilliped 3 followed after a delay of 15 to 20 ms in shore crabs by maxilliped 2 and then maxilliped 1, at a frequency of 18 to 20 Hz in crabs and 10 to 13 Hz in signal crayfish. The contraction of a single abductor muscle controls the power stroke (abduction) of each flagellum, which is accompanied by flaring of feather-like setae which increase its surface area. No muscle can bring about the return stroke (adduction). Release of an isolated flagellum from an imposed abduction is followed by a rapid recoil to its resting adducted position. The relationship between the extent of abduction and the angular velocity of the return stroke indicates the operation of a spring. Blue fluorescence under UV light, and its dependence on the pH of the bathing medium, indicates that resilin is present at the joint between an exopodite and flagellum, at the annuli of a flagellum and at the base of the setae. CONCLUSION: Resilin is progressively bent as a flagellum is abducted and resumes its natural shape when the joint recoils. Other distortions of the exopodites may also contribute to this spring-like action. The joint is therefore controlled by a single abductor muscle operating against a spring in which the elastic properties of resilin play a key role.

FEATURES OF CLINICAL SYMPTOMS AND SIGNS, HEMATOLOGICAL AND BIOCHEMICAL PARAMETERS IN CHILDREN WITH JOINT HYPERMOBILITY IN A LATE PERIOD UPON THE CHORNOBYL NPP ACCIDENT. / OSOBLYVOSTI KLINIChNOÏ SYMPTOMATYKY, GEMATOLOGIChNYKh TA BIOKhIMIChNYKh POKAZNYKIV U DITEY̆ Z GIPERMOBIL'NISTIu SUGLOBIV U VIDDALENYY̆ PERIOD PISLIa AVARIÏ NA ChORNOBYL'S'KIY̆ AES.

OBJECTIVE: establishing the types and frequency of disembriogenetic stigma in children with joint hypermobility given the clinical and laboratory features, genetic component and endocrine regulation of these disorders in a late period upon the accident. MATERIALS AND METHODS: Children (n = 109) inhabiting the radiologically contaminated territories and having the connective tissue dysplasia (CTD) signs were involved in the study. Diseases in family history, ossalgia complaints, fractures in a personal history, bone disembriogenetic stigma, joint hypermobility, type of somatic diseases, blood serum biochemical parameters (namely calcium, alkaline phosphatase, total protein, cholesterol, creatinine, iron, ferritin content), serum cortisol, free thyroxine, pituitary thyroid-stimulating hormone (TSH) levels, free amino acid composition in urine and radiation dose were considered. RESULTS: Radiation doses in children having the CTD ranged from (0.37 ± 0.11) mSv to (0.56 ± 0.10) mSv with no difference from that in those without CTD. Joint hypermobility (JHM) correlated with cancer in family history (rs = 0.53) and lower extremity varicose vein disease (rs = 0.40) (p < 0.05). Incidence of ossalgia, easy fatigability, and bone fractures was higher in children with CTD. Anomalies of the dentofacial system were first in line (38.5 %) in these children. Proportion of children with grade II JHM and platypodia was lower (rs = 0.42), but with lower extremity deformations was higher (rs = 0.68) (p < 0.05) vs. in the control group. Iron and ferritin deficiencies both with lymphocytosis were more common in children with CTD than in the comparison group (p < 0.05). The increased content of oxyproline, lysine, proline both with glycine deficiency were detected in children having the CTD, i.e. an imbalance of amino acids from the collagen content was observed featuring a predominance of catabolic processes over anabolic ones. There was a direct correlation between the TSH level and the JHM grade (rs = 0.49), although the values of hormone concentration in these children did not exceed the reference range (maximum values were 3.3 µIU/ml). CONCLUSIONS: The revealed abnormalities in amino acid content, ferrokinetics, and thyroid function indices can affect the collagen formation, organic matrix structure of bone tissue and significantly deregulate the hemato- poiesis. The later can underlie the pathways of haematologic malignancy development.

Consequences of modern anthropometric dimensions for radiographic techniques and patient radiation exposures.

Radiographic techniques are devised on the basis of anatomic dimensions. Inaccurate dimensions can cause radiographs to be exposed inappropriately and patient radiation exposures to be calculated incorrectly. The source of anatomic dimensions in common usage dates back to 1948. The objective of this study was to compare traditional and modern anthropometric data, use modern dimensions to estimate potential errors in patient exposure, and suggest modified technique guidelines. Anthropometry software was used to derive modern anatomic dimensions. Data from routine annual testing were analyzed to develop an x-ray generator output curve. Published tabulated data were used to determine the relationship between tissue half-value layer and kilovoltage. These relationships were used to estimate entrance skin exposure and create a provisional technique guide. While most anatomic regions were actually larger than previously indicated, some were similar, and a few were smaller. Accordingly, exposure estimates were higher, similar, or lower, depending on the anatomic region. Exposure estimates using modern dimensions for clinically significant regions of the trunk were higher than those calculated with traditional dimensions. Exposures of the postero-anterior chest, lateral chest, antero-posterior (AP) abdomen, male AP pelvis, and female AP pelvis were larger by 48%, 31%, 54%, 52%, and 112%, respectively. The dimensions of bony regions of the anatomy, such as the joints and skull, were unchanged. These findings are consistent with the idea that anatomic areas where fat is deposited are larger in the modern U.S. population than they were in previous years. Exposure techniques for manual radiography and calculations of patient dose for automatic exposure control radiography should be adjusted according to the modern dimensions. Population radiation exposure estimates calculated in national surveys should also be modified appropriately.

A comparison of joint stability between anterior cruciate intact and deficient knees: a new canine model of anterior cruciate ligament disruption.

Transection of the canine anterior cruciate ligament (ACL) is a well-established osteoarthritis (OA) model. This study evaluated a new method of canine ACL disruption as well as canine knee joint laxity and joint capsule (JC) contribution to joint stability at two time points (16 and 26 weeks) after ACL disruption (n=5/time interval). Ten crossbreed hounds were evaluated with force plate gait analysis and radiographs at intervals up to 34 weeks after monopolar radiofrequency energy (MRFE) treatment of one randomly selected ACL. Each contralateral ACL was sham treated. The MRFE treated ACLs ruptured approximately eight weeks (mean 52.5 days, SEM+/-1.0, range 48-56 days) after treatment. Gait analysis and radiographic changes were consistent with established canine ACL transection models of OA. Anterior-posterior (AP) translation and medial-lateral (ML) rotation were measured in each knee at 30 degrees, 60 degrees, and 90 degrees of flexion with and then without JC with loads of 40 N in AP translation and 4 Nm in ML rotation. A statistically significant interaction in AP translation included JC by cruciate (P=0.02), and there was a trend for a cruciate by time (P=0.07) interaction. Significant interactions in ML rotational testing included the presence of joint capsule (P=0.0001) and angle by cruciate (P=0.0012). This study describes a model in which canine ACLs predictably rupture approximately eight weeks after arthroscopic surgery and details the contribution of JC to canine knee stability in both ACL intact and deficient knees. The model presented here avoids the introduction of potential surgical variables at the time of ACL rupture and may contribute to studies of OA pathogenesis and inhibition. This model may also be useful for insight into the pathologic changes that occur in the knee as the ACL undergoes degeneration prior to rupture.

Three-dimensional diffuse optical tomography of bones and joints.

We present for the first time full three-dimensional (3D) volumetric reconstruction of absorption images of in vitro and in vivo bones and joints from near-infrared tomographic measurements. Imaging experiments were conducted on human finger and chicken bones embedded in cylindrical scattering media using a Clemson multichannel diffuse optical imager. The volumetric optical images were recovered with our 3D finite element based reconstruction algorithm. Our results show that 3D imaging methods can provide details of the joint structure/composition that would be impossible from two-dimensional imaging methods.

[Effect of somatotropin on the course and result of combined radiation and mechanical injury]. / Vliianie somatotropina na techenie i iskhody kombinirovannogo radiatsionno-mekhanicheskogo porazheniia.

In the experiment on rats it was shown that injection of somatotropin (1 ED/kg, i.m. at 1, 3, 5, 7 and 9 days) after combined irradiation and mechanical injury (4.5 Gy, LD50/30 and plural fractures) improved the overall condition of the rats and increased the survival. The drug accelerated the bone regeneration.

[Immunotropic therapy of rheumatoid arthritis (prerequisites, results and principles)]. / Immunotropnaia terapiia revmatoidnogo artrita (predposylki, rezul'taty, printsipy).

The author has summed up many-year investigation and literature data on immunological approaches to RA therapy including a study of the patients' immunological status, evaluation of the clinical efficacy and immunological effects of various therapeutic methods, and a study of the individual sensitivity of drugs in in vitro experiments. An indicator proposed by the author for the evaluation of clinicoimmunological therapeutic efficacy, expresses the true value of the method of RA therapy. Indices of the immune status necessary for a choice of patients and control of immunotropic therapy were defined; methods for the assessment of individual sensitivity to immunoreactive agents and principles of immunotropic therapy were presented.

[Use of laser irradiation in the complex ambulatory treatment of arthrosoarthritis]. / Primenenie lazernogo izlucheniia v kompleksnom lechenii artrozoartritov v usloviiakh polikliniki.

The article discusses experience with the treatment of 60 patients with arthrosoarthritis deformans of various large joints by the traditional conservative methods and with the use of laser radiation by an Uzor biomedical laser device. The authors noted a positive effect of laser radiation on the pathological processes developing in the region of the involved joint, which reduced the terms of treatment from 24.4 to 10.4 days and considerably reduced the number of recurrences in the immediate period.

Total-body irradiation produces late degenerative joint damage in rats.

PURPOSE: Premature musculoskeletal joint failure is a major source of morbidity among childhood cancer survivors. Radiation effects on synovial joint tissues of the skeleton are poorly understood. Our goal was to assess long-term changes in the knee joint from skeletally mature rats that received total-body irradiation while skeletal growth was ongoing. MATERIALS AND METHODS: 14 week-old rats were irradiated with 1, 3 or 7 Gy total-body doses of 18 MV X-rays. At 53 weeks of age, structural and compositional changes in knee joint tissues (articular cartilage, subchondral bone, and trabecular bone) were characterized using 7T MRI, nanocomputed tomography (nanoCT), microcomputed tomography (microCT), and histology. RESULTS: T2 relaxation times of the articular cartilage were lower after exposure to all doses. Likewise, calcifications were observed in the articular cartilage. Trabecular bone microarchitecture was compromised in the tibial metaphysis at 7 Gy. Mild to moderate cartilage erosion was scored in the 3 and 7 Gy rats. CONCLUSIONS: Late degenerative changes in articular cartilage and bone were observed after total-body irradiation in adult rats exposed prior to skeletal maturity. 7T MRI, microCT, nanoCT, and histology identified potential prognostic indicators of late radiation-induced joint damage.

Cryotherapy in inflammatory rheumatic diseases: a systematic review.

The aim of this article was to review current evidence about cryotherapy in inflammatory rheumatic diseases (therapeutic and biological effects). For therapeutic effects, we performed a systematic review (PubMed, EMBASE, Cochrane Library, LILACS databases, unpublished data) and selected studies including non-operated and non-infected arthritic patients treated with local cryotherapy or whole-body cryotherapy. By pooling 6 studies including 257 rheumatoid arthritis (RA) patients, we showed a significant decrease in pain visual analogic scale (mm) and 28-joint disease activity score after chronic cryotherapy in RA patients. For molecular pathways, local cryotherapy induces an intrajoint temperature decrease, which might downregulate several mediators involved in joint inflammation and destruction (cytokines, cartilage-degrading enzymes, proangiogenic factors), but studies in RA are rare. Cryotherapy should be included in RA therapeutic strategies as an adjunct therapy, with potential corticosteroid and nonsteroidal anti-inflammatory drug dose-sparing effects. However, techniques and protocols should be more precisely defined in randomized controlled trials with stronger methodology.

Scientific Meeting Report Radiosynovectomy--radionuclide treatment of synovitis in the peripheral joints.

On 25 February 2012, an interdisciplinary scientific meeting on the Radiosynovectomy of Peripheral Joints (RPJ) was held in a lecture hall of Nukleomed clinic in Warsaw.

Selectively induced death of macrophages in the synovial lining of murine knee joints using 10B-liposomes and boron neutron capture synovectomy.

OBJECTIVE: To investigate whether macrophages in the synovial lining can be selectively eliminated by local administration of an improved boron-10 ((10)B) containing liposome formulation combined with neutron irradiation (boron neutron capture synovectomy [BNCS]). METHODS: Disodium dodecahydrododecaborate (Na(2)(10)B(12)H(12)) was encapsulated into unilamellar liposomes ((10)B-liposomes). (10)B-liposomes were injected into the mouse knee joint. Amounts of (10)B in synovial tissue were measured over time using inductively coupled plasma-optical emission spectrometry (ICP-OES). Arthritis was induced in knee joints of mice. Joint inflammation and cartilage destruction was measured using histology. RESULTS: When a 10 microl (10)B-liposome solution (containing 40 microg (10)B) was injected into the murine knee joint, high concentrations of (10)B were measured in macrophages in the synovial lining (At 24 h 306+/-226 microg. g(-1) macrophages). Completing the BNCS by neutron irradiation of the legs 24 h after (10)B-liposome injection showed a clear selective depletion of macrophages in synovial lining of the knee joints. An estimated total physical dose of 13+/-9 Gy was given to the macrophages. When arthritis was induced in the macrophage-depleted joints, swelling of the knee was significantly lower as compared to the controls (53% and 79% lower at days 1 and 3, respectively). Histology confirmed the influx of inflammatory cells was strongly decreased and severe cartilage destruction was almost completely prevented. CONCLUSION: BNCS using an improved (10)B-containing liposome formulation can cause selective depletion of macrophages in the synovial lining of murine knee joints. As a result of this proof-of principle, future applications are recommended.