Type 1 Achilles tendon rupture caused by grooming trauma in a young dog.

Achilles tendon rupture is uncommon in small animal practice. A 9-month-old, female, mixed breed dog (weighing 2.2kg) was referred to our hospital with a primary complaint of right hind limb lameness. Complete right Achilles tendon rupture was diagnosed by physical examination and radiography. The tendon was surgically repaired the next day by using a three-loop and single near-far-far-near suture methods. Complete healing was achieved by 97 days post-surgery. This report describes the surgical technique used for complete Achilles tendon rupture repair in a young dog.

[Impact of preoperative 64-row multislice computed tomography for congenital aortic stenosis; report of a case].

A 63-year-old woman was diagnosed as having severe aortic stenosis (AS) with 98 mmHg peak pressure gradient detected by echocardiography. Since, preoperative enhanced 64-row multislice computed tomography (MSCT) showed bicuspid aortic valve with only 2 sinuses of Valsalva, congenital aortic stenosis was suspected. The left and right coronary arteries originated from respective sinus of Valsalva, and severely thickened cusps of aortic valve were detected clearly by preoperative 64-row MSCT. Aortic valve replacement with a 21 mm ATS mechanical bileaflet prosthesis was performed without aortic annulus enlargement. The postoperative course was uneventful and postoperative 64-row MSCT indicated good performance of the ATS valve. Preoperative 64-row MSCT could be useful to detect complex aortic valve disease in detail. Moreover. 64-row MSCT might be a reliable tool to evaluate valvular heart disease.

Size effects on insect hovering aerodynamics: an integrated computational study.

Hovering is a miracle of insects that is observed for all sizes of flying insects. Sizing effect in insect hovering on flapping-wing aerodynamics is of interest to both the micro-air-vehicle (MAV) community and also of importance to comparative morphologists. In this study, we present an integrated computational study of such size effects on insect hovering aerodynamics, which is performed using a biology-inspired dynamic flight simulator that integrates the modelling of realistic wing-body morphology, the modelling of flapping-wing and body kinematics and an in-house Navier-Stokes solver. Results of four typical insect hovering flights including a hawkmoth, a honeybee, a fruit fly and a thrips, over a wide range of Reynolds numbers from O(10(4)) to O(10(1)) are presented, which demonstrate the feasibility of the present integrated computational methods in quantitatively modelling and evaluating the unsteady aerodynamics in insect flapping flight. Our results based on realistically modelling of insect hovering therefore offer an integrated understanding of the near-field vortex dynamics, the far-field wake and downwash structures, and their correlation with the force production in terms of sizing and Reynolds number as well as wing kinematics. Our results not only give an integrated interpretation on the similarity and discrepancy of the near- and far-field vortex structures in insect hovering but also demonstrate that our methods can be an effective tool in the MAVs design.

The post-operative changes in the level of inflammatory markers after posterior lumbar interbody fusion.

Inflammatory markers such as the C-reactive protein (CRP), white blood cell count and body temperature are easy to measure and are used as indicators of infection. The way in which they change in the early post-operative period after instrumented spinal surgery has not been reported in any depth. We measured these markers pre-operatively and at one, four, seven and 14 days postoperatively in 143 patients who had undergone an instrumented posterior lumbar interbody fusion. The CRP proved to be the only sensitive marker and had returned to its normal level in 48% of patients after 14 days. The CRP on day 7 was never higher than that on day 4. Age, gender, body temperature, operating time and blood loss were not related to the CRP level. A high CRP does not in itself suggest infection, but any increase after four days may presage infection.

A phase II study of cisplatin and docetaxel administered as three consecutive weekly infusions for advanced non-small-cell lung cancer in elderly patients.

BACKGROUND: To evaluate the efficacy and safety of treatments for advanced non-small-cell lung cancer in elderly patients aged 75 years or older, we conducted a phase II study of cisplatin and docetaxel administered in three consecutive weekly infusions. PATIENTS AND METHODS: The eligibility criteria for the study included the presence of chemotherapy-naive advanced non-small-cell lung cancer, age > or =75 years, Eastern Cooperative Oncology Group performance status of 0 or 1, a measurable lesion, adequate organ functions and signed informed consent. The chemotherapy regimen consisted of cisplatin (25 mg/m(2)) and docetaxel (20 mg/m(2)) on days 1, 8 and 15 every 4 weeks. RESULTS: Between February 2000 and March 2002, 34 elderly patients with non-small-cell lung cancer were enrolled in the study and 33 patients were treated. Two complete responses and 15 partial responses were obtained for an objective response rate of 52% in 33 treated patients. The median survival period was 15.8 months, and the 1-year survival rate was 64%. Toxicities were mild with no grade 4 toxicities. Only grade 3 leukopenia (6%), neutropenia (12%), anemia (3%), hyponatremia (3%) and nausea/vomiting (3%) were observed. CONCLUSION: Cisplatin and docetaxel administered in three consecutive weekly infusions was safe and effective for the treatment of elderly patients with chemotherapy-naive non-small-cell lung cancer.

[The validity of revised death certificates (ICD-10) for ischemic heart disease in Oita City, Japan].

PURPOSE: Mortality statistics have recorded an increased number of deaths from ischemic heart disease (IHD) since death certificates were revised to reflect the International Classification of Diseases, tenth revision (ICD-10) in Japan, in 1995. However, it remains unclear whether the validity of IHD diagnosis improved after this revision. METHODS: We conducted the Oita Cardiac Death Survey to validate IHD certified deaths that occurred among residents aged 25-74 in Oita City, Japan (mean population = 273,000). Of the eligible 342 fatalities, 328 cases (95.0%) were examined by a review of the medical records and/or interviews with physicians. The MONICA criteria were applied and provided a reference standard against which to assess the validity of certified fatal IHD. Sensitivity (Se), positive predictive value (PPV), specificity (Sp) and negative predictive value (NPV) for IHD as the cause of death were analyzed, assuming that all validated IHD deaths were true. Multivariate logistic models were used to determine associations of false positive and false negative cases with sex, age at time of death and place of death. RESULTS: Vital statistics revealed 273 fatalities to be due to cardiac disease, including 143 from acute myocardial infarctions (AMI), 27 from other IHD, 52 from heart failure and 51 from other heart diseases. After validation, 25 'definite fatal AMI' and 71 'possible fatal AMI or IHD death' were identified among all subjects according to the MONICA criteria. In all, Se, PPV, Sp and NPV for IHD certified as the cause of death were 86.5% (95% Cl: 77.6-92.3), 50.3% (42.5-58.1), 64.7% (58.1-70.7), and 92.0% (86.5-95.5), respectively. PPV among persons aged 25-54 years was remarkably decreased. PPV and Sp among out-of-hospital deaths were significantly lower than for in-hospital deaths. Multivariate logistic models revealed out-of-hospital deaths and being aged 25-54 years to be significant predictors of false positive cases (odds ratio (OR) = 2.03, P < 0.001 versus in-hospital deaths and OR = 2.79, P < 0.05 versus ages of 65-74 years, respectively). CONCLUSIONS: Because false positive cases increased among certified IHD deaths after the revision, PPV and Sp percentages decreased. Out-of-hospital deaths and being aged 25-54 years were associated with increased possibility of false positive. Given our findings, IHD deaths in vital statistics may increase due to the tendency of physicians to certify IHD as the cause of death in cases without clear sign suggestive of other causes.

Anesthetic induction agents, sympathetic nerve activity and baroreflex sensitivity: a study in rabbits comparing thiopental, propofol and etomidate.

The mechanisms of arterial hypotension following intravenous anesthetic induction agents are multifactorial. The purpose of this study was to evaluate and compare the effects of thiopental, propofol and etomidate on hemodynamics, sympathetic outflow and arterial baroreflex sensitivity using not only neuraxis-intact but also totally baro-denervated rabbits. A total of 60 rabbits was anesthetized with urethane, tracheotomized, and mechanically ventilated with oxygen in nitrogen (FiO2 0.5). The left renal sympathetic nerve was isolated and placed on a bipolar electrode to record renal sympathetic nerve activity (RSNA). Thirty animals underwent a surgical preparation of total baroreceptor denervation. Bolus injections of an anesthesia induction dose of thiopental 4 mg/kg and twice the induction dose of propofol 4 mg/kg significantly decreased RSNA to the same extent (19.4+/-6.7 and 19.7+/-5.2% reduction, mean +/- SEM) and mean arterial pressure (MAP) also to the same extent (19.5+/-4.6 and 22.1+/-3.1% reduction) in the neuraxis-intact animals. RSNA was increased (34.5+/-6%) without reduction of MAP by an induction dose of etomidate, 0.3 mg/kg. Sympathetic barosensitivity was attenuated even 10 min after thiopental at 4 mg/kg or propofol at 4 mg/kg (68% and 54% of control, respectively). Propofol at 2 mg/kg (induction dose) and etomidate at 0.6 mg/kg decreased RSNA and MAP only in the baro-denervated animals. It was found from the barosensitivity study that patients can be hemodynamically unstable even though blood pressure has returned to normal after thiopental and propofol administration. Data suggest that etomidate can even stimulate the sympathetic nervous system and increase sympathetic outflow. It was also clearly found from the baro-denervated animal study that thiopental was stronger than propofol in directly suppressing sympathetic outflow at the induction dose.

Role of Notch-1 intracellular domain in activation of rheumatoid synoviocytes.

OBJECTIVE: Notch family proteins are transmembrane receptors that control cell fate and proliferation. Rheumatoid arthritis (RA) is characterized by activation and abnormal proliferation/differentiation of synoviocytes. We examined the expression of Notch-1 and its role in the activation of RA synoviocytes. METHODS: The expression of Notch-1 protein was detected by a specific antibody raised against the Notch-1 intracellular domain. Notch-1 messenger RNA (mRNA) expression in synoviocytes was analyzed by Northern blotting. Notch-1 protein expression was confirmed by Western blotting with anti-Notch-1 antibody. To analyze the role of Notch-1 in synoviocyte proliferation, we examined the effects of antisense Notch-1 oligonucleotides (ODNs) and MW167, a gamma-secretase inhibitor. RESULTS: Notch-1 protein and mRNA were detected in synovium from all study subjects. The nucleus of RA synoviocytes showed strong staining with anti-Notch-1 antibody, whereas there was predominantly cytoplasmic staining of normal and osteoarthritis (OA) synoviocytes. Western blotting showed a distinct approximately 63-kd protein detected by anti-Notch-1 antibody in nuclear extracts from RA synoviocytes, indicating that nuclear staining of RA synovium and synoviocytes is likely to be the result of nuclear localization of Notch-1 intracellular domain (NICD). Furthermore, tumor necrosis factor alpha (TNFalpha) increased NICD nuclear translocation in a dose-dependent manner. Antisense Notch-1 ODNs partially blocked the proliferation of RA synoviocytes and inhibited TNFalpha-induced proliferation in both OA and RA synoviocytes. In addition, gamma-secretase inhibitor, which blocks the production of NICD, also inhibited TNFalpha-induced proliferation of RA synoviocytes. CONCLUSION: Our results demonstrate the expression of Notch-1 in synoviocytes and the presence of Notch-1 fragment in the nuclei of RA synoviocytes and suggest the involvement of Notch-1 signaling in the TNFalpha-induced proliferation of RA synoviocytes.

Stromelysin-1 (MMP-3) in synovial fluid of patients with rheumatoid arthritis has potential to cleave membrane bound Fas ligand.

OBJECTIVE: To investigate the relationship between matrix metalloproteinases (MMP) and the soluble form of Fas ligand (sFasL) in the synovial fluid (SF) of patients with rheumatoid arthritis (RA), and to determine which MMP have a major role in cleaving FasL. METHODS: The concentrations of sFas and sFasL in SF from 48 patients with RA and 43 patients with osteoarthritis (OA) were measured using specific ELISA. The levels of different MMP (MMP-1, 2, 3, 7, 9) in SF were also measured by ELISA. The active forms of gelatinases were detected by gelatin zymogram. Human FasL-expressing transfected cells (hFasL/L5178Y) were used to investigate whether FasL is cleaved from membrane bound FasL. RESULTS: Significantly higher levels of MMP-1, 3, and 9 were found in SF from RA patients compared to OA patients, but MMP-7 was not detectable in either group. The concentrations of sFas and sFasL in SF were also higher in RA than in OA patients. However, there was no relationship between the concentration of sFas and sFasL. Among MMP, MMP-3 concentrations in SF were closely correlated with the level of sFasL and with disease activity of RA. Enzymatic cleavage assay indicated that MMP-3 has potential to cleave the FasL expressed on hFasL/L5178Y cells and to produce sFasL. CONCLUSION: There was significant correlation between the concentration of sFasL and MMP-3 in SF of patients with RA. In addition, our data indicate that the shedding of FasL may be regulated by MMP-3 in the joint of patients with RA.

Functional annotation of a full-length mouse cDNA collection.

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

[The amount of the loss of cyclosporine A dose correlated with the amount of leaching di (2-ethylhexyl) phthalate from polyvinyl chloride infusion tube].

An interaction between cyclosporine A (CyA) injection and infusion tubes were examined. We used polyvinyl chloride (PVC) and polybutadiene (PB) tubes. CyA injection (Sandimmun) was diluted (0.495 mg CyA/ml) with saline and dripped through infusion tubes. The amounts of unsolved substances, loss of CyA dose and leached di (2-ethylhexyl) phthalate (DEHP) during the drip study were compared. CyA was not lost into the PB tube and no DEHP was leached. Therefore, using PVC tube, 11.9 mg of CyA were lost with in 24 h after the beginning of the administration, and the concentration of leached DEHP amounted to 93.6 micrograms/ml at 12 h. We also investigated the effects of the component of the einfusion solution on the loss of CyA into PVC tube using saline, electrolyte maintenance solution, 5% glucose and 10% maltose. Sugar-containing solutions were found to have less effects than other solutions on the loss of CyA dose and DEHP leaching. The leaching of DEHP may be a major factor for the generation of unsolved substances and the loss of CyA dose. In the clinical use of CyA injection, PB tube is the best selection and the sugar-containing solution is a second selection when PB infusion tubes are hard to obtain.

Effects of combinations of anti-rheumatic drugs on the production of vascular endothelial growth factor and basic fibroblast growth factor in cultured synoviocytes and patients with rheumatoid arthritis.

OBJECTIVE: To examine whether different combinations of disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX), salazosulphapyridine (SASP) and dexamethasone (DEX; a steroid), act by inhibiting the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cultured synoviocytes, causing a decrease in their serum concentrations in patients with rheumatoid arthritis (RA). METHODS: The VEGF and bFGF concentrations in cultured synoviocytes and peripheral blood from patients with RA were measured by enzyme-linked immunosorbent assay and their serum concentrations were measured at two time points. RESULTS: BUC and GST inhibited VEGF production even when given alone, and a combination of BUC, GST and MTX with DEX also inhibited VEGF production. None of the DMARDs or DEX inhibited bFGF production when given alone, but a combination of SASP and GST inhibited the production of bFGF in cultured synoviocytes. Serum VEGF concentrations were significantly decreased 6 months after the commencement of medication compared with their concentrations before medication. CONCLUSION: Our results show that the effects of a combination of DEX with any two of BUC, GST, SASP and MTX on the production of VEGF and bFGF in cultured synoviocytes and on the serum concentrations of VEGF in patients with RA may be based on synergistic or additive effects of the drugs.

Comparison of fatal coronary heart disease occurrence based on population surveys in Japan and the USA.

BACKGROUND: Although vital statistics have indicated large Japanese-American differences in mortality rates for coronary heart disease (CHD), the magnitude of difference has not been documented well using comparable validation of cause of death. METHODS: Population-based fatal CHD data were compared between the Oita Cardiac Death Survey, Japan and the Atherosclerosis Risk in Communities (ARIC) Study, USA. Both studies (population: Oita City 198 093; the ARIC comunities 286 820) identified possible fatal CHD events (International Classification of Diseases, Ninth Revision [ICD-9]: 410-414, 250, 401-402, 427-429, 440, and 798-799) among residents aged 35-74 years during 1992-1993. Comparable criteria for classifying cause of death were applied. Sex-specific, age-adjusted mortality rates of CHD were calculated by place of death. RESULTS: In all, 330 deaths in Oita and 1398 in the ARIC communities had eligible ICD-9 death certificate codes; CHD codes (ICD-9 410-414) comprised 30.6% of investigated deaths in Oita and 58.6% in ARIC. For men, the non-validated rate ratio for CHD deaths (ARIC:Oita City) was 5.9 (95% CI : 4.2-8.5), which fell to 4.7 (95% CI : 3.5-6.4) with validation and inclusion of sudden deaths within one hour of onset as fatal CHD. For women, the overall non-validated rate ratio was 4.6 (95% CI : 2.8-7.6), which fell to 3.9 (95% CI : 2.4-6.3) with validation and but there was little further change when the sudden deaths were added. CONCLUSIONS: Our results suggest that differences in fatal CHD rates between Japanese and Americans were not as large as suggested by vital statistics when events were validated and sudden deaths were included.

Effects of sulfhydryl compounds on interleukin-1-induced vascular endothelial growth factor production in human synovial stromal cells.

We investigated the effects of various sulfhydryl compounds on interleukin-1 (IL-1)-induced vascular endothelial growth factor (VEGF) production in human synovial stromal cells (HSSC). HSSC stimulated by IL-1beta (100 ng/ml) produced VEGF and interleukin-6 (IL-6) in vitro. Monosulfhydryl compounds, N-acetylcysteine, D-penicillamine, tiopronin and the bucillamine-like disulfhydryl compound, compound A scarcely affected VEGF or IL-6 production at concentrations of 10(-5) and 10(-4) M. However, the disulfhydryl compound, bucillamine inhibited VEGF production but not IL-6 production at concentrations of 10(-5) and 10(-4) M. These results suggest that bucillamine may be a selective inhibitor of IL-1-induced VEGF production in HSSC, and that inhibition of VEGF production may require not only SH groups but also a specific chemical structure.

Circadian rhythms of seven heavy metals in plasma, erythrocytes and urine in men: observation in metal workers.

To elucidate circadian rhythms (variation within a day) of 7 toxic or essential metals in plasma and erythrocytes in relation to the rhythms in urine in men, 19 male metal foundry workers were examined; they were exposed to lead (Pb), zinc (Zn) and copper (Cu) occupationally but separated from the exposure during the study. Circadian rhythms were found for plasma concentration of Pb, cadmium (Cd), Zn, Cu and chromium (Cr) in the workers. Circadian rhythms were also found for Pb, inorganic mercury (Hg), Zn and Cr in erythrocytes and for all metals except Zn in urine. Both the plasma and urinary levels of Pb, Cd, Cu and Cr together with urinary excretion of Mn and creatinine tended to decrease during night hours; both the erythrocyte and urinary levels of Hg together with both the plasma and erythrocyte levels of Zn tended to increase during morning hours. The results of profile analysis suggested that the circadian rhythm of Pb in urine was affected more strongly by its plasma and erythrocyte rhythms than by the rhythm of creatinine in urine, i.e. the rhythm of glomerular filtration; the urinary rhythms of Cd, Cr, and Mn were affected more by the creatinine rhythm; and the urinary rhythm of Cu was affected by both its plasma and creatinine rhythms. On the other hand, the urinary rhythm of Hg was assumed to be independent of the creatinine rhythm and be affected by its erythrocyte rhythm. The present study suggested that different biological limit values might be needed for different hours of the day especially for shift workers who are exposed to various heavy metals. Instead, further studies should be conducted to find the adjustment methods by which no circadian rhythms are discerned.

Suppressive effects of remifentanil on hemodynamics in baro-denervated rabbits.

PURPOSE: To elucidate mechanisms by which remifentanil, an ultra-short-acting mu-opioid receptor agonist, causes hypotension and bradycardia. METHODS: Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were measured and recorded after bolus injections of 1, 2 or 5 microg x kg(-1) of remifentanil in neuraxis intact (n=6 for each dose) and baro-denervated rabbits (n=6 for each dose). Arterial baroreflex sensitivity was assessed by depressor tests. An additional six baro-denervated animals received remifentanil, 5 microg x kg(-1) after pretreatment with naloxone, 40 microg x kg(-1). RESULTS: All values were expressed in % change from baseline. In the neuraxis intact animals, MAP and HR were decreased briefly immediately after remifentanil injection. RSNA was increased dose-dependently: 137 +/- 8% (mean +/- SE), 170 +/- 14% (P < 0.05) and 225 +/- 29% (P < 0.05) after 1, 2 and 5 microg x kg(-1) remifentanil, respectively. RSNA was increased even after MAP and HR had returned to baseline values. The depressor tests revealed that remifentanil did not attenuate arterial baroreflex sensitivity. In the baro-denervated animals, MAP and HR decreased gradually to 77 +/- 3% (P < 0.05) and 94 +/- 1% (P < 0.05), respectively 300 sec after 5 microg x kg(-1) remifentanil. At that time, increased RSNA (159 +/- 9%, P < 0.05) had returned to baseline. Pretreatment with naloxone in the baro-denervated animals abolished these changes. CONCLUSION: Remifentanil decreases HR and MAP by its central vagotonic effect and by stimulating peripheral mu-opioid receptors. These effects appear to be counteracted and masked by its central sympathotonic effect and by maintaining arterial baroreflex integrity.

[Treatment of Bell's palsy with acyclovir and prednisolone].

Many current studies have suggested that herpes simplex virus is a probable cause of Bell's palsy, and that treatment with antiviral agents such as acyclovir might benefit the patients. In the present study, 69 patients with Bell's palsy were treated with oral administration of acyclovir (2000 mg/day) and prednisolone (60-40 mg/day) at Ehime University Hospital between Oct. 1995 and Dec. 1998. Patients enrolled in this study met the following criteria: 1) severe or complete paralysis with a score lower than 20 by the 40-point Japanese grading system, and 2) treatment started within 7 days of onset. The overall recovery rate was 95.7% (66/69). The rate in patients who started this treatment within 3 days after disease onset was 100%, and this early treatment was highly efficacious in the prevention of nerve degeneration and resulted in a significantly better recovery. By comparison, the recovery rate in patients whose treatment was started 4 days or more after onset was only 84.2%. All patients who were given a diagnosis of zoster sine herpete and treated with acyclovir-prednisolone had a good outcome. These results suggest that early treatment, within 3 days after palsy onset, is necessary for effective acyclovir-prednisolone therapy of Bell's palsy.

Isolation of calcifiable vesicles from aortas of rabbits fed with high cholesterol diets.

Advanced arterial wall calcification in atherosclerosis imposes a serious rupturing effect on the aorta. However, the mechanism of dystrophic calcification linked to hyperlipidemia, that causes atherosclerosis remains unknown. Emerging morphological and biochemical evidence reveals that calcifiable vesicles may have a role in plaque calcification. To determine whether a high cholesterol diet can induce arterial calcification and produce or activate calcifiable vesicles in aortas, a rabbit model was used. After 2 months of daily high lipid feeding (supplemented with 2% cholesterol and 6% peanut oil), typical atherosclerotic lesions developed. However, the mineral, if present in aortas, was insufficient to be detected by Fourier transform-infrared spectroscopy (FT-IR) or alizarin red staining, indicative of a non-calcifying stage of atherosclerosis. Small segments of thoracic aortas were digested in a crude collagenase solution to release calcifiable vesicles. Vesicles were also isolated from normal aortas as control to consider the possibility that membrane vesicles may be produced by crude collagenase digestion, which could cause the degradation of some cells. Calcifiable vesicles were precipitated at 300,000 x g after subcellular particles were removed by centrifugation at 30,000 x g. Calcifiability of isolated vesicles was then tested using calcifying media containing physiological levels of Ca2+ and Pi and 1 mM ATP. Electron microscopic observations showed that the isolated vesicles were heterogeneous in size and shape and capable of depositing electron dense particles. Fourier transform infrared spectroscopic analysis of the deposited particles revealed the presence of an amorphous mineral phase. The spectroscopic mineral to matrix ratios, related to the amount of mineralization, indicated that vesicles from cholesterol-fed rabbits produced more minerals than control vesicles obtained from the normal aortas. Alizarin red staining for mineral further demonstrated substantially higher calcifiability of the experimental vesicles. A 3-5 h exposure of the vesicles to calcifying media caused significant deposition of 45Ca and 32Pi in a vesicle protein-concentration dependent manner. Similar to previously reported observations with human atherosclerotic aorta vesicles, rabbit vesicles were enriched in ATP-hydrolyzing enzymes including Mg2+- or Ca2+-ATPase and NTP pyrophosphohydrolase that are implicated in normal and pathological calcification. Altogether, these observations suggest that accumulation of the released calcifiable vesicles, as a result of high cholesterol diets, may have a role in dystrophic calcification in hyperlipidemia-related atherosclerosis.

Lipoprotein(a) concentrations in healthy subjects in the Dominican Republic. Comparison with Japanese.

Previous studies have shown that serum concentrations of lipoprotein(a) [Lp(a)] are markedly different among different ethnic groups. We examined the serum levels of total cholesterol, high density lipoprotein (HDL) cholesterol and Lp(a) in apparently healthy subjects aged 20-69 years in Japan (n = 865) and the Dominican Republic (n = 1,893). Dominicans had significantly lower levels of total cholesterol and HDL cholesterol than Japanese. The distribution of Lp(a) concentrations were markedly skewed towards low levels in both Japanese and Dominicans. However, the mean Lp(a) concentration in Dominicans was approximately 2 times higher than in Japanese (21.7 +/- 23.7 vs 12.3 +/- 15.9 mg/dl, p < 0.001). This is possibly because the majority of Dominicans are of mixed Negroid and European blood.

Inhibitory effects of anti-rheumatic drugs on vascular endothelial growth factor in cultured rheumatoid synovial cells.

Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis and is constitutively expressed in the synovium of rheumatoid arthritis (RA). Over-expression of VEGF may play an important role in pathogenic vascularization and synovial hyperplasia of RA. In the present study, we examined whether disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX) and salazosulfapiridine (SASP), act by inhibiting the production of VEGF by cultured synovial cells of patients with RA. Treatment of cultured synoviocytes with lipopolysaccharide (LPS) significantly increased VEGF production by cultured synovial cells. BUC significantly inhibited LPS-induced VEGF production, while GST tended to inhibit the production of VEGF. The inhibitory effects on VEGF production were dose-dependent. In contrast, MTX and SASP did not affect VEGF production. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that BUC also inhibited LPS-induced VEGF mRNA expression in RA synovial cells. The present study provides the first evidence that BUC inhibits VEGF production and the expression of its mRNA in synovial cells of RA patients. Our results indicate that the anti-rheumatic effects of BUC are mediated by suppression of angiogenesis and synovial proliferation in the RA synovium through the inhibition of VEGF production by synovial cells.