Chondrocyte cytokine and growth factor expression in murine osteoarthritis

Eighty-five percent of male STR/ort mice develop osteoarthritic lesions of the knee joint by 35 weeks of age. We have developed a non-radioactive in-situ hybridization method using digoxigenin-labeled oligonucleotide probes to study the expression of the cytokines interleukin (IL) 1 alpha, Il-1 beta and IL-6 and the growth factors insulin-like growth factor-1 (IGF-1) and transforming growth factor beta (TGF beta 1) during the development of osteoarthritis (OA) in this model. Age- and sex-matched CBA mice, which do not develop OA, showed no detectable expression of any of the cytokines or growth factors studied. In contrast, 20-week-old STR/ort mice with no OA lesions showed positive expression [positive: (+)] for all the cytokines and growth factors studied. At 35 weeks of age, STR/ort mice with varying grades of OA showed positive (+) or strong (++) signals for both cytokines and growth factors throughout the tibial articular cartilage. The strongest signal was seen in areas where OA lesions were present. In areas of histologically-normal cartilage adjacent to the lesions, the signals were still positive but weaker. Fifty-week-old STR/ort mice with OA lesions showed a similar pattern of expression to 35-week-old mice. Thirty-five or 50-week-old STR/ort mice with no OA lesions had much reduced expression compared with those with OA lesions. These mice may be indicative of those STR/ort mice which do not develop OA. The results seen in the STR/ort together with previous biochemical analyses are consistent with an up-regulation of anabolic growth factors and catabolic cytokines in the prelesional stages of OA with anabolic effects predominating. At later stages of OA, the effects of catabolic factors appear to predominate and osteoarthritic lesions become evident.     

Intraparenchymatous vascular tumors of the testicle: report of a new case of cavernous hemangioma

The occurrence of a vascular tumour at the intraparenchymatous testicular level is a fact little reported in the literature. Searching for such events, 19 cases were found all of which showed benign clinical behaviour. The most commonly seen histological pattern is cavernous haemangioma (11 patients). Mean age at presentation is 19 years old and the most usual pre-operative diagnosis, germinal cell neoplasia. Since there are no specific ultrasound patterns that may allow to differentiate benign from malignant masses, inguinal orchiectomy is the choice treatment in this type of lesions. Furthermore, the case of a 44-year old patient with hypoechogenic solid mass in left testis who consulted for sporadic episodes of long-standing scrotal pain is presented. After radical exeresis of the gonad, the histological analysis showed existence of testicular cavernous haemangioma.     

Molecular changes in Entamoeba histolytica in response to bacteria

Entamoeba histolytica, the protozoan parasite, is the causative agent of amoebiasis. The degree of virulence, as inferred from invasiveness, of potentially pathogenic strains may be regulated by both host and parasite factors that determine the gut environment. One such factor that plays an important role is the bacterial flora in the gut. Previous studies have clearly shown that bacterial flora is an important determinant of virulence in E. histolytica. However, the exact nature of changes induced in E. histolytica in response to bacteria and their role in virulence is not clear. In this study the levels of a number of molecules potentially important in virulence mechanisms were determined in E. histolytica cells grown with and without normal human bacterial flora, using enzyme-linked immunosorbent assay. Significant changes were observed only after the E. histolytica cells had been adapted to grow with bacterial flora for a number of generations, and not in short term culture.     

Modeling the interaction between FK506 and FKBP12: a mechanism for formation of the calcineurin inhibitory complex

FK506 is a naturally occurring immunosuppressant whose mode of action involves formation of an initial complex with the cytosolic protein FKBP12. The composite surface of this complex then binds to and inhibits the protein phosphatase calcineurin (PP2B). To investigate why FK506 does not inhibit calcineurin directly we have conducted molecular modeling and conformational studies on published structures of FK506 both alone and in complex with FKBP12. From studies of the structure of FK506 in CDCl3 and Z-Arg32-ascomycin in water (a water soluble analogue of FK506) we suggest that the FK506 molecule can be viewed as consisting of three separate regions. The pipecolate region which extends from C24 to C10 including the pipecolate ring shows strongly conserved conformation in both solvents. The loop region which extends from C25 to C16 shows general conservation of the loop structure and the pyranose region made up of the pyranose ring and C15-C17 which shows highly variable conformation depending on solvent. Comparison of the structure of Z-Arg32-ascomycin in water with structures of FK506 bound to FKBP12 indicate that the conformation of the pipecolate region is conserved during the binding process. The conformation of the loop region was generally conserved but a significant reduction (approximately 1.7 A) in the diameter of the loop in the bound structure was observed. The conformation of the pyranose ring and C15-C17 region was found to be significantly altered in the bound structure resulting in displacements of the C13 and C15 methoxyl groups of 2.8 and 3.5 A, respectively. From computer models and molecular dynamics simulations of interactions between FK506 and FKBP12 we suggest that the conformational changes observed in bound FK506 are induced by the interaction between the 80's loop of FKBP12 and the pyranose ring of FKBP12. These interactions result in the formation of a complex with the both correct shape and surface polarity for interaction with calcineurin.     

Prosthodontic considerations when using implants for orthodontic anchorage

Between 8 December 1995 and 16 January 1996 seven laboratory confirmed cases of septicaemia owing to infection with Neisseria meningitidis serogroup C strains and one highly probable case of meningococcal septicaemia occurred in three electoral wards in south Rotherham and the Retford area of north Nottinghamshire. All cases occurred among children aged 1-17 years. One patient died. The public health response to this outbreak was the largest community prophylactic antibiotic and immunization programme against meningococcal infection, to date, in the United Kingdom. The target group for each Health Authority was 8900 for Rotherham Health Authorities and 8000 for North Nottinghamshire Health. Local logistical factors led to differences in the implementation of the programme by each Health Authority. At the completion of each programme, 8320 doses of vaccine had been administered (92.5 per cent coverage) during the Rotherham Health Authorities programme and 7660 (95.7 per cent coverage) during the North Nottinghamshire Health programme. The additional financial cost of the exercise amounted to approximately Pounds 125000 for each Health Authority. This paper describes the evolution of the outbreak, the decision-making process resulting in the immunization programme in each Health Authority, the implementation of each programme, problems identified and lessons learned.     

The prevalence of early postpartum psychiatric morbidity in Dubai: a transcultural perspective

The surface roughness of artificial blood contacting devices is an important surface property that is closely related to blood cell trauma. The present study investigated the effect of the surface roughness of a pump housing on hemolysis in an impeller-type centrifugal blood pump, a pivot bearing supported Gyro C1E3 pump. The purpose of the study was to determine which part of a housing has the greatest surface roughness effect on hemolysis in a centrifugal pump. Seven Gyro C1E3 pumps were prepared, each with a smooth surface impeller and a housing with differing areas of altered surface roughness. Both top and bottom housings were divided into half subregions, each with the same area. Seven test pumps were produced by subjecting various subregions of the housings to vapor polishing and sandblasting. The treated surfaces were then examined by a surface profile instrument. Using these 7 pumps with different areas of altered housing roughness, in vitro hemolysis tests were performed simulating cardiopulmonary bypass (5 L/min, 350 mm Hg). The results of this study are as follows. First, the surface roughness of the top housing had a greater effect on hemolysis than that of the bottom housing. Second, on the surface of the top housing, the surface roughness of the outer half area had a greater effect on hemolysis than that of the inner half area. Third, on the surface of the bottom housing, the surface roughness of the inner half area had a greater effect on hemolysis than that of the outer half area. These findings concur with previous studies of flow patterns in pumps. Thus, it is expected that the method in this study, comparative in vitro hemolysis tests of the pumps with surfaces of the same roughness but different locations, can be used to detect the high shear area inside a pump.     

Prospective use of intramuscular triamcinolone acetonide in pseudogout

OBJECTIVE: To prospectively assess the efficacy of intramuscular (i.m.) triamcinolone acetonide in the treatment of pseudogout. METHODS: Fourteen patients with crystal proven pseudogout presenting with an acute attack within 5 days of onset were treated with intramuscular triamcinolone acetonide 60 mg and followed for 30 days. Patients with inadequate response were eligible for a 2nd triamcinolone acetonide injection on Day 1-2. RESULTS: Twelve patients had contraindication to nonsteroidal antiinflammatory agents (NSAID). Acute arthritis was monoarticular in 10 patients, and involved 2 or more joints in 4 patients. All patients had good clinical response to triamcinolone acetonide based on restoration of near baseline joint range of motion and joint circumference, and at least 50% improvement in patient and physician global assessment. Major clinical improvement occurred by Day 1-2 (2 patients), Day 3-4 (11 patients), and Day 10-14 (one patient). Six patients required a 2nd triamcinolone acetonide injection on Day 1-2. Toxicities were not observed. CONCLUSION: I.m. triamcinolone acetonide appears to be safe, well tolerated, and effective in the treatment of pseudogout. It may be a reasonable alternative therapy when NSAID are contraindicated, and for polyarticular attacks where intraarticular corticosteroids are impractical.     

Comparative catabolism of prothrombin and antithrombin in normal and alloxan-diabetic rabbits

Previous studies have shown that alloxan-induced diabetes in rabbits effects a slower release of plasma proteins from the liver, a slower synthesis of 35S-glycosaminoglycan in the extracellular matrix of the arterial wall, and a concurrent reduction in the fractional catabolic rates of several plasma proteins. In the present study, the catabolism of two hemostatic proteins, prothrombin and antithrombin, are compared in alloxan-induced diabetic rabbits (of 6 months' duration) and age-matched control rabbits. Differentially radiolabeled prothrombin and antithrombin were injected intravenously, and arterial blood was sampled over a 7-day period to measure the clearance from plasma. A three-compartment model was used to determine the fractional catabolic rate and compartmental distribution of the two proteins. As observed for other plasma proteins, the whole-body fractional catabolic rates (jt) for prothrombin and antithrombin were significantly less in diabetic rabbits (prothrombin, 0.33 d-1; antithrombin, 0.27 d-1) than in control rabbits (prothrombin, 0.37 d-1; antithrombin, 0.30 d-1; P < .001 and P < .005, respectively). In absolute terms, the catabolism of antithrombin and prothrombin in diabetic rabbits was 5.1 and 6.2 mg.kg-1.d-1, respectively, equivalent to a molar ratio for antithrombin to prothrombin of 0.94. For the control rabbits, catabolism accounted for 6.3 mg.kg-1.d-1 of antithrombin and 7.3 mg.kg-1.d-1 of prothrombin, equivalent to a molar ratio of 1.01. The fractional distribution of these proteins was not significantly different within the intravascular and extravascular spaces in diabetic and control rabbits. The decreased catabolic rates observed for prothrombin and antithrombin in diabetic rabbits conform with results obtained previously for other plasma proteins, and probably reflect a generally decreased rate of plasma protein production by diabetic rabbit liver compared with control liver.     

The adenohypophysis of Mediterranean yellowtail, Seriola dumerilii (Risso, 1810): an immunocytochemical study

The adenohypophysis (ADH) of the Mediterranean yellowtail was studied using the peroxidase-antiperoxidase technique. Human corticotropin (ACTH) (1-24)-immunoreactive (ir) cells were found bordering the neurohypophysis (NH) and salmon prolactin (PRL)-ir cells were arranged in thick cords, both in the rostral pars distalis (RPD). Gonadotropin (GTH)-, thyrotropin (TSH)- and growth hormone (GH)-ir cells were observed in the proximal pars distalis (PPD). Anti-chum salmon GTH I and anti-chum salmon GTH II immunostained the same cells in the outermost part of the ADH at the level of the PPD and the PI. In addition to these cells, some cells grouped in the inner areas of the posterior PPD were revealed by catfish alpha, beta-GTH antiserum. Human beta-TSH-ir cells formed small groups and discontinuous strands in the PPD often in contact with the NH. Tilapia GH-ir cells formed cords mainly surrounding the NH in the central PPD, while cod somatolactin- and alpha MSH-ir cells mainly surrounded the NH branches in the PI.     

Monitoring early response of experimental brain tumors to therapy using diffusion magnetic resonance imaging

Quantitative magnetic resonance imaging was performed to evaluate water diffusion and relaxation times, T1 and T2, as potential therapeutic response indicators for brain tumors using the intracranial 9L brain tumor model. Measurements were localized to a column that intersected tumor and contralateral brain and were repeated at 2-day intervals before and following a single injection of 1,3-bis(2-chloroethyl)-1-nitrosourea (13.3 mg/kg). Tumor growth was measured using T2-weighted magnetic resonance imaging to determine the volumetric tumor doubling time (Td) before (Td = 64 +/- 13 h, mean +/- SD, n = 16) and after (Td = 75 +/- 9 h, n = 4) treatment during exponential regrowth. Apparent diffusion coefficient of untreated tumors was independent of tumor volume or growth time, whereas relaxation times increased during early tumor growth. Diffusion displayed the strongest treatment effect and increased before tumor regression by 55% 6-8 days following treatment. Changes in relaxation times were also significant with increases of 16% for T1 and 27% for T2. Diffusion and relaxation times returned to pretreatment levels by 12 days after treatment. Histological examination supports the model that the observed increase in diffusion reflects an increase of extracellular space following treatment. Furthermore, the subsequent apparent diffusion coefficient decrease is a result of viable tumor cells that repopulate this space at a rate dependent on the surviving tumor cell fraction and recurrent tumor doubling time. Serial tumor volume measurements allowed determination of log cell kill of 1.0 +/- 0.3 (n = 4). These results suggest that diffusion measurements are sensitive to therapy-induced changes in cellular structure and may provide an early noninvasive indicator of treatment efficacy.