Antimicrobial susceptibility surveillance of bacterial isolates recovered in Japan from odontogenic infections in 2013.

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to ß-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with ß-lactamase inhibitor showed low MIC90 values.

Secondary Bilateral Orbital Involvement from Primary Non-Hodgkin Lymphoma of the Cheek.

We describe a patient with oculomotor nerve palsy due to secondary orbital infiltration from the primary malignant lymphoma of the cheek. The patient was a 78-year-old female who had non-Hodgkin lymphoma (diffuse large B cell lymphoma [DLBCL]) of the cheek. The patient received chemotherapy and local radiation therapy. The combined treatment brought about complete remission. About 6 months after the last treatment the patient began to have left blepharoptosis and impaired vision. Findings from ophthalmological and neurosurgical examinations suggested no intraorbital or intracranial lesions. Repeated MRI and CT scans also showed no such lesions. One month later, the patient suddenly had a left oculomotor disturbance, diplopia and exophthalmus, followed by right oculomotor nerve palsy. An MRI revealed bilateral intraorbital tumors. Recurrence at the orbital tissue of malignant lymphoma originated from the left cheek appeared to cause the ophthalmological symptoms. Salvage chemotherapy was performed and her ocular symptoms were recovered. However, the patient died approximately 10 months after recurrent orbital tumor onset.

Effect of Intraarticular Triamcinolone Acetonide Injection for Wrist Pain in Rheumatoid Arthritis Patients: A Statistical Investigation.

BACKGROUND: A significant number of patients on long-term treatment and users of biologics complain of wrist pain due to synovial proliferation and arthropathic changes. Synovectomy or joint arthroplasty is often indicated for such patients, but many refuse surgery. For these patients triamcinolone acetonide was injected into the dorsum of the wrist, and evaluated the clinical benefit and safety of the wrist joint. METHODS: We injected triamcinolone acetonide into the dorsum of the wrist. We evaluated the clinical benefit and safety of intraarticular triamcinolone acetonide by analyzing data on (1) the number of injections, (2) decrease in visual analog scale pain, (3) changes in carpal height ratio, radio carpal distance ratio, and radial rotation angle in X-ray imaging, and (4) the adverse reactions of triamcinolone acetonide injection on the subcutaneous tissue and extensor tendons. RESULTS: 1. The number of injections per patient over 3 years 8 months was 1 for 44 wrists, 2 for 21 wrists, 3 for 17 wrists, 4 for 6 wrists, 5 for 3 wrists, 6 for 3 wrists, 7 for 2 wrists, 9 for 2 wrists, 12 for 4 wrists, and 13 for 1 wrist. 2. The overall mean VAS improved from 79 mm at baseline to 11 mm post-injection. 3. In the grade I and II group, CHS, RCDR and RRA were not statistically significant. In the grade III and IV group, CHR showed a significant decrease. 4. Neither subcutaneous atrophy nor extensor tendon rupture was reported. CONCLUSIONS: More than 90% of patients of all disease grades responded to an average of 1 to 4 injections per year.

Chemical Composition and Aroma Evaluation of Essential Oils from Skunk Cabbage (Symplocarpus foetidus).

Two sample preparation methods, namely hydrodistillation (HD) and solvent-assisted flavor evaporation (SAFE), have been used to investigate the essential oils of the aerial parts (leaves and stems) of Symplocarpus foetidus, a plant with a characteristic odor, by gas chromatography mass spectrometry (GC-MS). Characteristic aroma-active compounds in the oils were detected by GC-Olfactometry (GC-O) and aroma extract dilution analysis (AEDA). From the HD method, the main compounds in the oil were found to be p-vinyl-guaiacol (15.5%), 2-pentyl-furan (13.4%), and (Z)-ligustilide (9.5%). From the SAFE method, the main compounds were 2-butoxy-ethanol (49.6%), ethyl-pentanoate (4.5%), and mesitylene (4.0%). In HD oil, the most intense aroma-active compounds were 2-pentyl-furan (flavor dilution factor (FD) = 32, odor activity value (OAV) = 57), p-vinyl-guaiacol (FD = 16, OAV = 41), and dimethyl disulfide (FD = 16, OAV = 41). In SAFE oil, the main aroma-active compounds were 2-butoxy ethanol (FD = 32, OAV = 16), and 2-methoxy thiazole (FD = 32, OAV = 25).

Effect of irreversible electroporation on three-dimensional cell culture model.

Irreversible electroporation (IRE) is a new treatment to necrotize abnormal cells by high electric pulses. Electric potential difference over 1 V across the plasma membrane permanently permeabilizes the cell with keeping the extracellular matrix intact if the thermal damage due to the Joule heating effect is avoided. This is the largest advantage of the IRE compared to the other conventional treatment. However, since the IRE has just started to be used in clinical tests, it is important to predict the necrotized region that depends on pulse parameters and electrode arrangement. We therefore examined the numerical solution to the Laplace equation for the static electric field to predict the IRE-induced cell necrosis. Three-dimensionally (3-D) cultured cells in a tissue phantom were experimentally subjected to the electric pulses through a pair of puncture electrodes. The necrotized area was determined as a function of the pulse repetition and compared with the area that was estimated by the numerical analysis.

Age- and sun exposure-dependent differences in 8-hydroxy-2'-deoxyguanosine and N-(carboxymethyl)lysine in human epidermis.

Aging and exposure to sunlight are two major factors in the deterioration of skin function. In this study, thirty-six fixed human skin samples from sun-exposed and unexposed areas from young and old individuals were used to evaluate the localization of oxidative stress according to levels and distribution of 8-hydroxy-2'-deoxyguanosine and N(ε)-(carboxymethyl)lysine in samples using immunohistochemistry. In the epidermis of the young, negligible amounts of 8-hydroxy-2'-deoxyguanosine and N(ε)-(carboxymethyl)lysine were detected in unexposed areas, whereas nuclear 8-hydroxy-2'-deoxyguanosine and cytoplasmic N(ε)-(carboxymethyl)lysine were increased in the lower epidermis in sun-exposed areas. In contrast, the aged presented prominent nuclear 8-hydroxy-2'-deoxyguanosine and nuclear N(ε)-(carboxymethyl)lysine in the epidermis of unexposed areas, concomitant with dermal increase in N(ε)-(carboxymethyl)lysine. However, the immunostaining of 8-hydroxy-2'-deoxyguanosine and N(ε)-(carboxymethyl)lysine revealed a decrease in the epidermis of sun-exposed areas in the aged. These results suggest an age-dependent difference in the adaptation and protective mechanisms of the epidermis against sunlight-associated oxidative stress, thus necessitating distinct standards for evaluation in each age group. Further investigation is warranted to elucidate underlying molecular mechanisms.

Characterization of comprehensive appearances of skin ageing: an 11-year longitudinal study on facial skin ageing in Japanese females at Akita.

BACKGROUND: Facial appearance is regarded as a typical index of ageing. However, people of the same age do not necessarily show the same degree of the facial appearance. The ageing of facial skin proceeds relatively slowly and therefore requires long-term follow-up to elucidate the mechanism of ageing changes. OBJECTIVES: The purpose of this study was to identify facial skin parameters contributing the subjective impression of the overall ageing and characterize the degree of skin ageing by a 11 year longitudinal skin monitoring. METHODS: One-hundred-eight healthy Japanese females excluded outside workers aged 5-64 at 1999, and lived in Akita, Japan till 2010 were enrolled. Facial images were collected to quantify various skin optical parameters. Skin colour, hydration and barrier function were measured with Chromameter, Corneometer and TEWAmeter, respectively. The visual evaluation of the overall facial skin ageing impression was also carried out. The skin parameters contributing visible impression of skin ageing were identified by variable importance in projection analysis, and the degree of facial skin ageing over 11 years was statistically classified by a cluster analysis. RESULTS: Facial skin parameters that comprehensively influenced visible skin ageing, including hyperpigmented spots, wrinkles and texture were studied. The Skin Ageing Score calculated from these three skin factors was used to classify the subjects into a mild, age-appropriate, and severe skin ageing group. The mild skin ageing group maintained significant better both skin optical and physical conditions. CONCLUSIONS: Variability and classification of the degree of facial skin ageing appearance were studied from this longitudinal research.

Whether to excise a lipofibroma of the median nerve.

A 28-year-old man presented with a lipofibroma of the median nerve of the left hand. We released the carpal tunnel, did a neurolysis, and biopsied of the median nerve together with a distal fasciotomy of the forearm. Two years after the operation, the paraesthesiae of the middle finger had improved but was still present to a lesser degree. Initial considerations about treatment should be directed toward biopsy and alleviation of the compression neuropathy, rather than total excision.

Flexor digitorum profundus avulsion of the left little finger through enchondroma of the distal phalanx: pull-out wire technique treatment without bone graft.

This case report describes the rare occurrence of a flexor digitorum profundus (FDP) avulsion of the left little finger in association with a pathological fracture of an enchondroma. The enchondroma was treated by simple curettage without bone graft. The FDP tendon was re-attached to the distal phalanx using the pull-out technique with a non-absorbable polyethylene suture. We recommend simple curettage without bone grafting in cases of enchondroma of the distal phalanx in which the bone defect is small.

Salivary 8-OHdG: a useful biomarker for predicting severe ED and hypogonadism.

INTRODUCTION: Erectile and endothelial dysfunction are common pathologies of multiple cardiovascular risk factors and are considered longitudinal predictors of cardiovascular events. Oxidative stress and decreases in testosterone levels play an important role in the pathogenesis of endothelial dysfunction. AIM: We sought to determine whether the severity of erectile dysfunction (ED) was associated with individual levels of testosterone and oxidative stress, and whether treatment with a phosphodiesterase type 5 inhibitor could reduce oxidative stress and increase testosterone availability. METHODS: We evaluated the association of salivary 8-hydroxy-2'-deoxyguanosine (8-OHdG), salivary testosterone, International Index of Erectile Function-erectile function domain (IIEF-EF) scores, and Medical Outcome Study (MOS) 36-item Short-Form Healthy Survey (SF-36) questionnaires in 128 middle-aged male volunteers. We investigated the changes in testosterone levels, salivary 8-OHdG levels, IIEF-EF scores, and SF-36 scores in 20 ED patients (according to the IIEF-EF) who took 50 mg of sildenafil once a week for 6 months. MAIN OUTCOME MEASURES: IIEF-EF scores were used to assess ED severity. Antioxidant status was defined by salivary 8-OHdG. Salivary testosterone was used to evaluate serum bioavailable testosterone availability. RESULTS: Salivary 8-OHdG (OR = 9.88, 95% CI: 1.52-64.10), salivary testosterone (Odds ratio [OR] = 0.96, 95% CI: 0.93-0.98), and vitality on the SF-36, version 2 (SF-36 v2) (OR = 0.92, 95%CI: 0.84-0.98) were significantly associated with the severity of ED in healthy volunteers. Treatment with sildenafil for 6 months significantly increased the total serum testosterone (426.4 +/- 174.8 vs. 569.6 +/- 146.1 ng/dL, P = 0.021) and salivary testosterone levels (56.1 +/- 22.3 vs. 110.0 +/- 48.4 pg/mL, P < 0.001), whereas it decreased salivary 8-OHdG levels (2.30 +/- 0.23 vs. 0.90 +/- 0.05 ng/mL, P = 0.0046). CONCLUSIONS: Salivary 8-OHdG is a useful biomarker for predicting severe ED and hypogonadism in middle-aged men. Once-a-week treatment with sildenafil can have beneficial effects on men's health by decreasing oxidative stress and increasing testosterone levels.

Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer.

BACKGROUND: We evaluated the efficacy and feasibility of high-intensity-focused ultrasound (HIFU) for localized prostate cancer. METHODS: Seventy patients received HIFU using Sonablate((R)) 500 (Focus Surgery, IN, USA). In patients whose cancer was confined to only one lobe by multi-regional biopsies, total peripheral zone and a half portion of transitional zone were ablated (focal therapy). Otherwise, patients received whole organ ablation (whole therapy). Scheduled biopsies were performed at 6 and 12 months after treatment. Pre- and post-HIFU serum testosterone levels were measured. Result The 2-year biochemical disease-free survival (DFS) rates in patients at low, intermediate and high risk were 85.9, 50.9 and 0%, respectively, (P = 0.0028). After 12 months, 81.6% (40/49) of patients were biopsy negative; 84.4% in patients who received whole therapy, whereas 76.5% in those with focal therapy. The 2-year biochemical DFS rates for the patients at low and intermediate risk was 90.9 and 49.9%, respectively, in patients with whole therapy, whereas 83.3 and 53.6% in patients with focal therapy. In patients without neoadjuvant androgen deprivation, serum testosterone levels continuously decreased after whole therapy, whereas no changes were seen in those with focal therapy. The patients whose follow-up biopsies were positive tended to have significantly higher changes in prostate-specific antigen levels than biopsy-negative patients. CONCLUSIONS: In patients with low-risk prostate cancer, HIFU monotherapy resulted in comparable immediate cancer control with other modalities. Particularly, focal therapy might offer a feasible minimally invasive therapeutic option, which maintained serum testosterone level. To our knowledge, this is the first report that whole, but not focal, therapy affects the serum testosterone level.

Visualization and characterization of UVB-induced reactive oxygen species in a human skin equivalent model.

Reactive oxygen species (ROS) play important roles in the process of ultraviolet-induced skin damage or photoaging. Although many enzymatic and chemical methods have been developed for evaluating ROS, evaluation methods for ROS generation in living systems are quite limited. Here we propose a unique system to visualize UVB-induced ROS and investigate the biological impact of ROS. In brief, a human skin equivalent model (HSEM) was exposed to UVB. Emitted luminescence from the HSEM was visualized and semi-quantified by using a chemiluminescent probe (CLA) and an ultra low-light imaging apparatus. The effects of anti-oxidative compounds such as ascorbate, beta-carotene, superoxide dismutase (SOD), and yeast ferment filtrate (YFF) on the HSEM were evaluated by semi-quantification of emitted chemiluminescence (CL) intensities, MTT assay and 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining. Visualization of time- and space-dependent dynamics of ROS generation in the HSEM was successfully achieved by utilizing a sensitive two-dimensional ultra-low light luminograph. Treatments with beta-carotene and SOD effectively suppressed CL intensity, indicating the generation of 1O2 and O2 .- in the HSEM under UVB exposure. Tested anti-oxidative compounds also attenuated UVB-induced CL and ameliorated the induced skin damages in terms of 8-OHdG formation and cell death. As a conclusion, this model is useful for not only visualizing the production of UVB-induced ROS in real-time but also evaluating the efficacy of topically applied anti-oxidative compounds to suppress ROS generation and attenuate sequential chemical and biological responses.

[A case of a giant adrenal myelolipoma in a man with spinal cord injury].

A 38-year-old man in a wheelchair for spinal cord injury from a traffic accident was referred to our hospital with complaint of dull right flank pain. The patient had a history of skin ulcer formation on both toes due to poor circulation. Abdominal ultrasonography and computed tomographic scan revealed a huge retroperitoneal tumor compressing the right kidney. Serum levels of cortisol, adrenocorticotropic hormone, aldosterone, adrenalin, noradrenalin, urinary levels of vanillylmandelic acid, homovanillic acid, 17-ketosteroid and 17-hydroxycorticosteroid were all within normal limits. Combining all preoperative diagnostic information, the possibility of retroperitoneal liposarcoma could not be thoroughly ruled out. The patient consented to undergo resection of the tumor with the right kidney. Prior to the scheduled operation simulation of the positioning on the operation table was done to evaluate the compressing pressure. During operation decompressing pads were used to minimize the compressing pressure and intermittent pneumatic compression was also used to prevent pressure ulcer and facilitate circulation to the lower extremities. Five thousands units of heparin (FragminR, Pfizer, USA) was used daily to prevent deep vein thrombosis until the patient could use his wheelchair. Perioperative rehabilitation was conducted by a team of physical therapists. The excised tumor weighed 1,320 g. Pathologic diagnosis was an adrenal myelolipoma. Convalescence was uneventful and the patient was discharged on the 10th post operative day. Between 1992 and 2006, 80 cases of adrenal myelolipoma were reported in Japan. Our case was found to be the second largest one. We reviewed these 80 cases and discussed the diagnosis and treatment strategy of the adrenal myelolipoma. We also discussed the perioperative management for patients with spinal cord injury.

Real-time chemiluminescent imaging and detection of reactive oxygen species generated in the UVB-exposed human skin equivalent model.

The objective of this study is to image and detect reactive oxygen species (ROS) generated in the UVB-exposed three-dimensional human skin equivalent model (HSEM), EpiDermtrade mark 200, because the alternative system needs to be urgently established as a replacement for the skin of experimental animals. Evidence that the ROS generation is enhanced in the skin of live animals after the UVB exposure was already obtained, by using the real-time chemiluminescent (RT-CL) method consisting of a sensitive CL probe (CLA) and an ultra-low light imaging apparatus. In this study, CL emission due to the reaction of CLA with endogenously generated ROS increased significantly in the UVB-treated HSEM compared with that in the intact HSEM, the maximum level being observed at a dose of 27mJ/cm(2). ROS under UVB exposure was identified to be ()O2- and (1)O(2) as observed by suppressive effects of SOD and beta-carotene topically applied on sample surface before the UVB exposure. The results for UVB-induced ROS generation in HSEM were consistent with those observed in the skin of live animals. HSEM combined with the RT-CL method was shown to be useful system not only to predict UVB-induced ROS-related skin responses in human but also to find protective agents against UVB-stimulated oxidative stress in place of animals and ex vivo human skin.

Inhibition of inflammatory nitric oxide production and epidermis damages by Saccharomycopsis Ferment Filtrate.

BACKGROUND: Yeast extracts have been shown to perform anti-inflammatory and cytoprotective activities. However, the effects of yeast extracts on lipopolysaccharide (LPS)-induced nitric oxide (NO) production and epidermal damages are still unclear. OBJECTIVE: To investigate the effect of Saccharomycopsis Ferment Filtrate (SFF) on LPS-induced NO production in RAW264.7 macrophages and epidermal damages. METHOD: RAW264.7 cells are incubated with LPS (25 ng/mL) and different concentrations of SFF. The amount of NO production is detected by Griess reaction. Additionally, the expression of inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) are detected by Western blotting. Artificial epidermis is also used to mimic the in vivo condition to investigate the protective effects of SFF on LPS- or ultraviolet radiation (UVR)-induced damages by histology and electron microscopy. RESULTS: The results show that SFF addition inhibits LPS-induced NO production and iNOS protein expression in a concentration-dependent manner without notable cytotoxicity in RAW264.7 cells, and induction of HO-1 protein expression by SFF was observed. Interestingly, both HO-1 inducers, hemin and CoCl2, significantly attenuated LPS-induced NO production and iNOS protein expression. The addition of CoCl2 potentiated the inhibitory effect of SFF on LPS-induced NO production. It seems that HO-1 protein participates in SFF inhibition of LPS-induced NO production. Furthermore, SFF exhibits significant protective effect on LPS- or UVR-induced damages in the artificial epidermis via histological and electron microscopic observations. CONCLUSION: This study provided the first evidence to indicate the beneficial effects of SFF in preventing NO production in macrophages and damages in epidermis, respectively. It suggests that SFF possesses potential to be further developed.

Balance of tumor necrosis factor alpha and interleukin-10 in a buccal infection in a streptozotocin-induced diabetic rat model.

This study evaluates the local levels of proinflammatory cytokine, tumor necrosis factor alpha (TNF-alpha), and anti-inflammatory cytokine, interleukin-10 (IL-10), in an experimental buccal abscess of a diabetic rat model. We prepared a buccal cavity induced by injection of carrageenin in a diabetic rat (blood glucose, 460.6 +/- 54.7 mg/dl, mean +/- SE) induced by streptozotocin (STZ). The buccal abscess was formed by the direct inoculation of Streptococcus pyogenes S-8 (2 x 10(7) cfu) into the buccal cavity at day 5 after carrageenin injection. Cytokine levels in the exudate of the buccal abscess were measured by enzyme-linked immunosorbent assay for 48 h after infection. Bacterial counts, weighing of exudate, and histological analysis were also performed. The mean TNF-alpha levels in the buccal abscess exudate of the diabetic group, which were generally higher than those of the control group, tended to increase over time until 48 h after infection, while the TNF-alpha levels in the control group peaked at 24 h after infection and then decreased. The IL-10 levels in the diabetic group remained almost unchanged until 48 h after infection, while the IL-10 levels in the control group were significantly higher than in the diabetic group at 12-24 h after infection. The mean ratio of TNF-alpha to IL-10 levels was 1.17-1.67 in the diabetic group, which was higher than the 0.26-0.69 of the control group. The bacterial counts in the buccal abscess and the weight of exudate were significantly higher in the diabetic group compared to the control group at 36-48 h. Histological findings showed that inflammatory cell infiltration was remarkable in the diabetic group compared to that of the control group. These results suggest that the elevated proinflammatory TNF-alpha levels and decreased anti-inflammatory IL-10 levels, which are produced at local infection sites, may at least in part be related to the severity of inflammation in this rat model with diabetes induced by STZ.

[Clinico-statistical analysis of renal cell carcinomas in patients on hemodialysis].

Eleven patients on hemodialysis that were surgically treated for renal cell carcinomas during the recent 10 years at our institutes were clinically analyzed. Patients' ages at presentation ranged from 35 to 70 years with an average of 54.8 years. Nine of the 11 patients were males and 2 were females. Periods between the introduction of hemodialysis and the presentation ranged from 1 to 21 years with an average of 11.7 years. The most frequent cause of hemodialysis was chronic glomerulonephritis. Five patients presented with macroscopic hematuria, which was the most frequent clinical manifestation. Transperitoneal nephrectomy through a lumbar oblique incision was performed in 9 of 12 surgical procedures. Transperitoneal resection and retroperitoneal endoscopic resection were performed on 2 patients and 1 patient, respectively. Blood transfusion was performed on 2 patients with retroperitoneal hemorrhage before or after operation and 2 patients with pre-existing renal anemia. Pathologically, 9 patients had pT1a disease. Patients were followed up for up to 7 years and 11 months. One patient died of the disease and 2 patients died of unknown causes. In conclusion, surgical removal of renal cell carcinomas was well tolerated, safe and effective treatment in patients under hemodialysis.

Local levels of interleukin-1beta, -4, -6 and tumor necrosis factor alpha in an experimental model of murine osteomyelitis due to staphylococcus aureus.

The purpose of this study is to evaluate local levels of interleukin-1 beta (IL-1 beta), -4 (IL-4), -6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha), in a model of murine osteomyelitis due to Staphylococcus aureus. Cytokine levels in supernatants derived from bone homogenates were determined by enzyme-linked immunosorbent assay, for 28 days following the direct implantation of murine tibiae with S.aureus. Levels of IL-1 beta and IL-6 in infected bone were elevated in the early post-infection period and then decreased. In contrast, TNF-alpha levels remained elevated 3 to 28 days post-infection, while IL-4 levels were elevated late in the course of infection. The histopathology of infected bone showed predominant infiltration of inflammatory cells and bone resorption 3 to 7 days after infection, and bone resorption and adjacent areas of formation 14 to 28 days after infection. These results suggest that the elevated IL-1 beta and IL-6 levels induced by infection may be related to bone damage mainly in the early phase of infection, and that TNF-alpha and IL-4 may at least in part be associated with histopathological changes, including both bone resorption and formation in the later phase of this osteomyelitis model.

Inhibitory effect of roxithromycin on the local levels of bone-resorbing cytokines in an experimental model of murine osteomyelitis.

OBJECTIVES: The purpose of this study was to evaluate the inhibitory effect of roxithromycin on the production of interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in a murine tibial osteomyelitis model using Staphylococcus aureus. METHODS: Cytokine levels in supernatants derived from bone homogenates were measured by enzyme-linked immunosorbent assay for 28 days, after oral administration of roxithromycin at 5 mg/kg/day. RESULTS: There was no significant difference in IL-6 levels between a group receiving roxithromycin administration and a group not receiving roxithromycin. IL-1beta and TNF-alpha levels were significantly lower for the administration group after 7-14 days and after 21-28 days, respectively. However, a significant difference in bacterial counts in bone between the groups was not observed. CONCLUSION: These results indicate that roxithromycin suppresses the local expression of IL-1beta and TNF-alpha, and may exhibit an anti-inflammatory effect in this osteomyelitis model.