HSP70-Hom NcoI POLYMORPHISM AND HLA-ASSOCIATIONS IN THE FINNISH POPULATION AND IN PATIENTS WITH ANKYLOSING SPONDYLITIS OR REACTIVE ARTHRITIS

The NcoI polymorphism of the HSP70-Hom gene was investigated in the Finnish population and in two HLA-B27-associated autoimmune diseases. The two HSP70-Hom alleles were shown to be strongly associated to some specific HLA-B/DR haplotypes in random Finnish population and the segregation of the alleles as a part of these haplotypes was confirmed in 18 families. In addition, the HSP70-Hom alleles of 31 patients with ankylosing spondylitis (AS) and 38 with reactive arthritis (ReA) were compared with each other and with 56 unrelated healthy HLA-B27 positive individuals. The results indicated that the HSP70-Hom polymorphic variation is not connected independently to the different pathogenesis of AS and ReA, as no statistically significant differences between the patient groups and/or controls could be found. The HSP70-Hom status was investigated also in 28 homozygous HLA typing cells and when compared with previously published results of HSP70-1 and HSP0-2 polymorphisms, it appeared that these three MHC Class-III linked HSP70 genes segregated in fixed allelic combinations.     

Protein and lipid metabolism in nephrotic infants on peritoneal dialysis after nephrectomy

Congenital nephrotic syndrome of the Finnish type (CNF) is associated with protein deficiency despite substantial protein supplementation in the nephrotic state before nephrectomy. Different protein intakes (2.5 vs. 3.7 g/kg per day) in hypoproteinaemic children on continuous cycling peritoneal dialysis (CCPD) were studied. Lipids were also measured to determine whether severe atherogenic abnormalities seen during nephrosis improved after nephrectomy. Growth was normal or became normal with both protein intakes. Serum pre-albumin and transferrin concentrations became normal. Total protein (57±3.0 vs. reference limits 60–75 g/l) and albumin (28±5.0 vs. reference limits 30–50 g/l) concentrations improved but remained below normal, even with the higher protein intake. Muscle mass determined by measuring femoral quadriceps muscle thickness using ultrasound was markedly reduced in all patients at nephrectomy. It improved (P<0.05) in all but 2 patients who had several bacterial infections, but reached normal level in only 3 patients within 6 months. Plasma total, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) triglyceride concentrations decreased (P<0.05,P<0.05 andP<0.01, respectively) and VLDL, LDL and high-density lipoprotein (HDL) particles contained less triglyceride than in the nephrotic state. HDL cholesterol concentrations increased by 28% [0.58±0.22 mmol/l during nephrosis, 0.81±0.21 mmol/l on CCPD after nephrectomy (P<0.05)] but remained below the level of 1.38±0.75 mmol/l in normal controls (P<0.001). If compared with controls there were still significant abnormalities in lipoprotein concentrations on CCPD. Hence, a protein intake of 2.5 g/kg per day representing 140% of the recommended dietary allowance is sufficient to maintain normal growth and improve nutritional and protein status in CNF patients on CCPD. Although lipid levels improved they remained abnormal.     

Antibody producing capacity to the bacteriophage phi X174 in yersinia arthritis.

Antibody production in response to the primary immunogen bacteriophage phi X174 was investigated in 14 patients with previous yersinia arthritis (YA) and in 15 controls. HLA-B27 occurred in 10 patients with YA and in three controls. After primary and secondary immunisation the antibody responses were essentially similar both in patients with YA and controls. Consequently our results suggest that antibody response to a foreign antigen does not differ between patients with YA and a normal control population. In addition, there was no difference in peak antibody responses between individuals with HLA-B27 and those without HLA-B27.     

Subjective and objective orthodontic treatment need among orthodontically treated and untreated Finnish adolescents

Abstract Subjective orthodontic treatment need was studied in a sample of 340 Finnish adolescents with and without previous orthodontic treatment. The subjects, who were attending two schools preparing students for college, first filled in a questionnaire. Of the 340 subjects, 24.4% of the treated and 24.0% of the untreated expressed subjective orthodontic treatment need (NS). For the clinical examination, 110 subjects were systematically sampled from four groups; subjects who had received orthodontic treatment in the past and a) felt, b) did not feel subjective orthodontic treatment need and subjects who had not received orthodontic treatment in the past and c) felt, d) did not feel subjective orthodontic treatment need. A total of 106 subjects were examined by an orthodontist. Objective treatment need was assessed by using the Treatment Priority Index. Of those clinically examined, 29.4% of the treated subjects were still found to be in objective need of orthodontic treatment; among the untreated subjects, the corresponding figure was 54.5% (P < 0.05). The sensitivity of the orthodontist to detect treatment need felt by the adolescents was, among the treated, 40.0% and the specificity 75.0%. Among the untreated subjects the corresponding figures were 75.9% and 69.2%. Of those treated who had objective treatment need, 40.0% expressed the need themselves (NS). However, of the untreated who had objective treatment need, 73.3% expressed such a need (P < 0.001). Subjects judged to have a very attractive denial appearance (IOTN, Aesthetic Component) were more often detected among those treated than among the untreated. As a clear discrepancy can be observed between objective and subjective treatment need estimates, in orthodontic counseling an understanding of how the patient perceives his/her dentition is essential.     

Half of the patients with an acute hip fracture suffer from hypovitaminosis D: a prospective study in southeastern Finland

Vitamin D deficiency may be one important contributing risk factor for an osteoporotic fracture among elderly. We analyzed serum 25-hydroxyvitamin D [S-25(OH)D] status in patients with an acute hip fracture in southeastern Finland (61°N). Consecutive patients with a fresh hip fracture ( n =223) in two Finnish hospitals during 12 months and 15 months were registered prospectively. S-25(OH)D concentrations (nmol/l) were measured by radioimmunoassay-method. Hypovitaminosis D was defined as S-25(OH)D <37.5 nmol/l and severe hypovitaminosis D:<20 nmol/l. The highest threshold of S-25(OH)D in our analysis was >74 nmol/l. The seasonal variation in S-25(OH)D concentrations was followed. Hypovitaminosis D was found in 53% of the patients. In 9% hypovitaminosis D was severe. Half (50%) of the patients living in their own homes, 55% of those in residential homes, and 61% of institutionalized elderly had hypovitaminosis D. Patients who used both vitamin D and calcium supplement had S-25(OH)D levels between 37.5 nmol/l and 74 nmol/l and >74 nmol/l more often than non-users ( Wx =3.85, p =0.0001). Most (41/61) of the patients who sustained the fracture during the late summer months had S-25(OH)D concentration 37.5 nmol/l, whereas, in winter months the situation was quite the opposite (24/67) ( Wx =3.42, p =0.0006). Twenty-two percent (50/223) had S-25(OH)D concentration >50 nmol/l and four patients >78 nmol/l. Half of the patients with a hip fracture suffered from hypovitaminosis D. The situation was worst in institutional and residential care, although there are personnel for taking care of vitamin D supplementation. In the late summer, one-third and in late winter two-thirds of the patients suffered from hypovitaminosis D. The geographical location of Finland indicates extensive efforts to increase the use of vitamin D supplements among elderly.     

Insulin resistance, LDL particle size, and LDL susceptibility to oxidation in pediatric kidney and liver recipients

BACKGROUND: Dyslipidemia is common after solid organ transplantation. We have described hypertriglyceridemia in about 50% of our pediatric kidney, and in about 30% of our liver recipients. The aim of the present study was to find out whether this post-transplantation hypertriglyceridemia after pediatric solid organ transplantation is associated with insulin resistance and the occurrence of small, dense low-density lipoprotein (LDL). METHODS: Fifty kidney and 25 liver recipients (aged 4 to 18 years) on triple immunosuppression, and 181 control children participated in the study for an average of 5.3 and 6.4 years after kidney and liver transplantation (range 1 to 11 years), respectively. Homeostasis model assessments for insulin resistance (HOMA) were calculated and fasting lipoprotein lipid profile, apolipoprotein A-I and B concentrations, LDL particle diameter, and indices of LDL susceptibility to copper-induced oxidation determined. RESULTS: Kidney patients had significantly higher serum total, high-density, and low-density lipoprotein cholesterol, triglyceride, apolipoprotein A-I and B concentrations than liver patients or control subjects (P < 0.003 for all). HOMA indices higher than the 95th percentile of Canadian normal children were seen in 50.0% of kidney (of liver 41.2%) recipients younger than 11 years, and in 27.3% of older recipients (of liver 37.5%). Smaller sized LDL or LDL of increased oxidizability was not more frequent in patients than in control children. CONCLUSION: Pediatric kidney recipients had significantly higher lipid and insulin concentrations than healthy control children. Combined hyperlipidemia and features of the dysmetabolic syndrome were common in children after kidney and liver transplantation. However, no small, dense LDL, or LDL prone to oxidation was seen in either group.     

Pharmacokinetics and response to pravastatin in paediatric patients with familial hypercholesterolaemia and in paediatric cardiac transplant recipients in relation to polymorphisms of the SLCO1B1 and ABCB1 genes

AIMS: Our aim was to investigate associations between the single nucleotide polymorphisms (SNPs) in the SLCO1B1 (encoding OATP1B1) and ABCB1 (encoding P-glycoprotein) genes with the pharmacokinetics and efficacy of pravastatin in children with heterozygous familial hypercholesterolaemia (HeFH) and in paediatric cardiac transplant recipients. METHODS: Twenty children with HeFH (aged 4.9-15.6 years) and 12 cardiac transplant recipients (aged 4.4-18.7 years and receiving triple immunosuppressive medication) who had participated in previous pharmacokinetic and pharmacodynamic studies with pravastatin were genotyped for the -11187G > A and 521T > C SNPs in the SLCO1B1 gene and for the 2677G > T/A and 3435C > T SNPs in the ABCB1 gene. RESULTS: Two HeFH patients with the -11187GA genotype had a 81% lower peak plasma pravastatin concentration (Cmax) (difference in means -13.9 ng ml(-1), 95% CI -21.1, -6.7; P < 0.001) and a 74% smaller area under the plasma concentration-time curve (AUC0, infinity) (-25.3 ng ml(-1) h, 95% CI -35.6, -15.0; P < 0.0001) and significantly greater increase in high density lipoprotein (HDL) cholesterol after 2 months treatment with pravastatin than patients with the reference genotype. No significant differences were seen in the pharmacokinetics or effects of pravastatin between HeFH patients with the SLCO1B1 521TC and 521TT genotypes. The cardiac transplant recipients with the SLCO1B1 521TC genotype (n = 3) had a 46% lower Cmax (-67.7 ng ml(-1), 95% CI -135.7, 0.3; P = 0.055) and 62% lower AUC(0,24 h) (-228.5 ng ml(-1) h, 95% CI -402.7, -54.3; P = 0.016) and a shorter half-life (t1/2) (0.9 +/- 0.1 vs. 1.3 +/- 0.4 h, P = 0.015) of pravastatin than those with the reference genotype. Decreases in total and low-density lipoprotein cholesterol by pravastatin were significantly smaller, and the increase in HDL-cholesterol was greater in the transplant recipients with the 521TC genotype compared with patients with the 521TT reference genotype. CONCLUSIONS: In children with HeFH and in paediatric cardiac transplant recipients receiving immunosuppressive medication, the -11187G > A and SLCO1B1 521T > C SNPs were associated with decreased plasma concentrations of pravastatin. These differences are opposite to those seen previously in healthy adults. The mechanisms underlying these phenomena are unclear and warrant further study.     

Crystallization of glycine with ultrasound

Sonocrystallization has proved to be an efficient tool to influence the external appearance and structure of a crystalline product obtained by various crystallization methods. The present work focuses on high intensity sonocrystallization of glycine by varying amplitude of ultrasound with an ultrasound frequency of 20 kHz at two temperature ranges 40–50 and 20–30 °C in a jacketed 250-ml cooling crystallizer equipped with a stirrer. The polymorph composition of the obtained crystals was analyzed with a temperature variable X-ray powder diffractometer (XRPD). XRPD results showed that, besides the operating temperature, the glycine polymorphism was affected also by insonation. This was especially the case at the lower temperature range. Furthermore, based on the heat balance within the crystallizer, an increase in required cooling capacity was presented as a function of increasing ultrasound power. This study also showed, the higher the ultrasound amplitude the smaller the crystals obtained.