Impaired early bone formation in periodontal fenestration defects in dogs following application of insulin-like growth factor (II). Basic fibroblast growth factor and transforming growth factor beta 1

Abstract. Effects of a topically applied growth factor combination on fibroblast migration, collagen fiber formation and bone regeneration were studied in standardized periodontal defects in 4 beagle dogs. Following elevation of facial mucoperiosteal flaps, fenestration defects, 3 mm in diameter, were made through the cortical bone and into the dentin of maxillary and mandibular teeth. Collagen sponges, impregnated with 200 ng insulin-like growth factor II, 20 ng basic fibroblast growth factor and 6 ng transforming growth factor beta 1 were fitted to defects randomly in right or left quadrants and the flaps repositioned and sutured. Contralateral control defects received the collagen with vehicle only. Experimental procedures were staggered to allow observations of healing 3, 7, 10, and 14 days after surgery. Histometric analysis showed no differences in fibroblast and collagen density between control and growth factor defects. Bone regeneration was significantly greater in control than in growth factor defects 10 and 14 days after surgery. The rate of healing generally appeared more affected by intra-dog variations or procedural variations than by the growth factor combination.     

Similarities in Skeletal Muscle Strength and Exercise Capacity Between Renal Transplant and Hemodialysis Patients

Exercise intolerance is common in hemodialysis (HD) and renal transplant (RTx) patients. Aim of the study was to assess to what extent exercise capacity and skeletal muscle strength of RTx patients differ from HD patients and healthy controls and to elucidate potential determinants of exercise capacity in RTx patients. Exercise capacity, muscle strength, lean body mass (LBM) and physical activity level (PAL) were measured by cycle-ergometry, isokinetic dynamometry, DEXA and Baecke Questionnaire, respectively, in 35 RTx, 16 HD and 21 controls. VO2peak and muscle strength of the RTx patients were significantly lower compared to controls (p<0.01), but not different compared to HD patients. In RTx patients, strength (p<0.001), PAL (p=0.001) and age (p=0.045) were significant predictors of VO2peak. Muscle strength was related to LBM (p=0.001) and age (p=0.001), whereas gender (p<0.001) and renal function (p=0.01) turned out to be significant predictors of LBM. No effects of corticosteroids were observed. Exercise capacity and muscle strength seem equally reduced in RTx and HD patients compared to controls. In RTx patients, muscle strength and PAL are highly related to exercise capacity. Renal function appears to be a significant predictor of LBM, and through the LBM, of muscle strength and exercise capacity.     

Living-Related Versus Deceased Donor Pediatric Liver Transplantation: A Multivariate Analysis of Technical and Immunological Complications in 235 Recipients

Timely access to a living donor (LD) reduced pretransplant mortality in pediatric liver transplantation (LT). We hypothesized that this strategy may provide better posttransplant outcome. Between July 1993 and April 2002, 235 children received a primary LT from a LD (n = 100) or a deceased donor (DD) (n = 135). Demographic, surgical and immunological variables were compared, and respective impact on posttransplant complications was studied using a multivariate analysis. Five-year patient survival rates were 92% and 85% for groups LD and DD, respectively (p = 0.181), the corresponding graft survival rates being 89% and 77% (p = 0.033). At multivariate analysis: (1) type of donor (DD) was correlated with higher rate of artery thrombosis (p < 0.012); (2) biliary complication rate at 5 years was 29% and 23% for groups LD and DD, respectively (p = 0.451); (3) lower acute rejection incidence could be correlated with type of donor (DD) (p = 0.001), and immunosuppressive therapy (tacrolimus) (p < 0.001). We conclude that (1) according to the multivariate analysis, LT with LD provided similar patient and graft outcome, when compared to DD; (2) a higher rate of artery thrombosis and a lower rate of rejection were observed in group DD; (3) this study confirms the efficacy of tacrolimus for immunoprophylaxis, whatever the type of organ donor is.     

Characterization of in vitro metabolites of the aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole by liquid chromatography-mass spectrometry and NMR.

The tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) exhibits the highest aryl hydrocarbon receptor (AhR) binding affinity reported so far. In different cells, in vitro, both extracts of UV-irradiated tryptophan and the synthesized pure compound FICZ induce a rapid and transient expression of AhR-regulated genes. The transient induction suggests that the biotransformation gene battery induced by AhR activation takes part in a metabolic degradation of the ligand, whereby a low steady-state level is regained. The down-regulation of AhR-regulated gene expression was previously shown to be dependent on cytochrome P450 1A1 (CYP1A1). Metabolism of FICZ generates five major metabolites, which appeared as three peaks (M1-M3) in the high performance liquid chromatography. The aim of the present study was to use rat liver S9 from Aroclor-pretreated rats to produce large enough quantities of FICZ metabolites for structure characterization and to determine their product precursor relationship. NMR analysis of large combined fractions of the metabolites indicated that M3 and M2 contained 2 isomers, respectively. By means of liquid chromatography-mass spectrometry (negative ion electrospray mode) and NMR spectroscopy (by (1)H-NMR, correlation spectroscopy, and nuclear Overhauser effect spectroscopy techniques) five metabolites of FICZ were identified, and their structures were elucidated. The molecular weights of the two M3 isomers were 300 and both M2 and M1 compounds demonstrated molecular weights of 316, corresponding to addition of one (M3) and of two oxygen (M2 and M1), respectively. The structures were assigned as 2- and 8-hydroxy (M3), 2,10- and 4,8-dihydroxy (M2) and 2,8-dihydroxy derivatives of indolo[3,2-b]carbazole-6-carboxaldehyde (6-formylindolo[3,2-b]carbazole).     

P-31 MR spectroscopy of skeletal and cardiac muscle metabolism in patients with systemic sclerosis: A multiple case study

Three-dimensionally localized proton-decoupled phosphorus-31 magnetic resonance (MR) spectroscopy of skeletal and cardiac muscle was performed in six patients with systemic sclerosis. Cardiac (n = 9) and skeletal (n = 6) spectra were also obtained in healthy volunteers. Metabolite ratios and intracellular pH were determined from the spectra of skeletal and cardiac muscle. The phosphocreatine-to-adenosine triphosphate ratio was normal for both skeletal and cardiac muscle in patients with systemic sclerosis. The pH values of skeletal muscle were similar in patients and control subjects (7.13 ± 0.02 vs 7.12 ± 0.01, respectively). In skeletal muscle, the inorganic phosphate-to-phosphocreatine ratio in patients was increased relative to that of control subjects (0.106 ± 0.014 vs 0.086 ± 0.006, respectively; P =.02). P-31 MR spectroscopy showed no abnormalities in the myocardium of patients with systemic sclerosis. Assessment of the inorganic phosphate-to-phosphocreatine ratio in peripheral skeletal muscle may be helpful for assessing disease activity.     

Acute arteriolar vasoconstriction following furosemide in conscious spontaneously hypertensive rats

In a previous study in conscious spontaneously hypertensive rats (SHR), we observed an immediate decrease in the cardiac index (CI) and an increase in the total peripheral resistance index (TPRI) following the administration of furosemide. The present study was designed to evaluate the regional hemodynamic effects and the involvement of sinoaortic baroreceptors in the increase in TPRI. In SHR instrumented for the measurement of central hemodynamics, 8 mg.kg-1 furosemide decreased CI from 31.0 +/- 2.5 ml.min-1.100 g bw-1 by 9.5 +/- 1.3 ml.min-1.100 g bw-1 (n = 7). TPRI increased maximally from 5.7 +/- 0.8 by 2.7 +/- 0.5 mm Hg.min.100 g bw.ml-1. The effect on TPRI was not affected by sinoaortic denervation (SAD) to abolish arterial baroreflexes. However, furosemide induced a significantly greater decrease in CI (-12.6 +/- 1.2 ml.min-1.100 g bw-1; n = 7) after SAD. Furosemide effectively reduced the mean arterial pressure in SAD SHR (-21 +/- 9 mm Hg) but not in sham-denervated SHR. Furosemide (8 mg.kg-1) reduced renal, mesenteric and hindquarter blood flow to a comparable extent (approximately 20%) in intact SHR. The reduction in renal flow at 3.5 min after injection (-17.9 +/- 4.1%; n = 8) was significantly greater than the reduction in mesenteric (-7.1 +/- 4.7%) and hindquarter blood flow (-4.2 +/- 3.7%), suggesting that the renal bed responds faster. Thereafter, the flow reductions in the three beds were not different. The results show that furosemide causes a general vasoconstriction in conscious SHR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Kupffer cell depletion in vivo results in clearance of large-sized IgA aggregates in rats by liver endothelial cells.

We investigated the clearance kinetics and tissue distribution of different sized IgA in normal and macrophage-depleted rats. Rats were injected iv with liposomes containing dichloromethylene diphosphonate (DMDP). DMDP treatment resulted in complete depletion of liver macrophages 24-48 h after administration. Normal and macrophage depleted rats were injected intravenously with monomeric, dimeric, polymeric or aggregated polymeric IgA (AIgA) and assessed for blood clearance and tissue distribution. In normal rats, clearance of IgA was size dependent, i.e. a faster clearance with increasing size. No differences in clearance kinetics were observed of the different sized IgA between normal and DMDP-treated rats. TCA non-precipitable radioactivity, a measure for degradation of IgA, was found in the circulation of normal and DMDP-treated rats after AIgA administration. The liver was the main organ responsible for the clearance of IgA in normal and DMDP-treated rats. Immunofluorescence studies on liver biopsies indicated that AIgA was associated with Kupffer cells in normal rats. Electron microscopical studies revealed that the AIgA was internalized and located in vesicles in Kupffer cells. In DMDP-treated rats the AIgA was associated with endothelial cells and electron microscopy studies showed that this AIgA was taken up by endothelial cells. These data show that rat liver endothelial cells are able to bind, internalize and degrade AIgA in situations where Kupffer cells are absent, and that these cells may play an important role in the handling of AIgA and IgA-immune complexes.     

Combined hypophyseal function test in children with homozygous beta-thalassemia]

Nowadays, endocrine problems like retarded sexual maturation and growth deficiency, lead to substantial suffering in patients with beta-thalassemia major. The aim of the present study is the differentiation between a possible insufficiency of the pituitary gland and dependent target organs, respectively. 12 patients (age 1.9-18.10 years) were examined by means of a combined pituitary function test. The corticotropic axis turned out to be normal as shown by a regular stimulation of cortisol in all patients tested. The thyrotropic function was unaffected in all children: elevated levels of TSH pointed to primary hypothyroidism. Pubertal values of LH and FSH were found in only 3 out of 7 patients at pubertal age. In 10 out of 12 children, stimulation led to a rise in STH levels above 10 ng/ml. On the whole, there was no evidence for pituitary insufficiency in beta-thalassemia major.     

Elevated body mass index and mortality risk in the elderly

The purpose of this report was to perform a systematic review and meta-analysis of the studies examining the impact of an elevated body mass index (BMI) on mortality risk in elderly (> or =65 years) men and women. A variance-based method of meta-analysis was used to summarize the relationships from available studies. The summary relative risk of all-cause mortality from the 26 analyses that included a risk estimate for a BMI within the overweight range was 1.00 (95% confidence intervals, 0.97-1.03). The summary relative risk of all-cause mortality for the 28 analyses that included a risk estimate for a BMI within the obese range was 1.10 (1.06-1.13). These calculations indicate that a BMI in the overweight range is not associated with a significantly increased risk of mortality in the elderly, while a BMI in the moderately obese range is only associated with a modest increase in mortality risk.