Occurrence of anti-C1q antibodies in IgA nephropathy

Background: The pathogenic mechanisms and the antigens involved in the establishment and progress of IgA nephropathy are unknown. As antibodies against C1q have been reported to correlate with SLE nephritis, we analysed the occurrence of these antibodies in IgA nephropathy in order to investigate the possibility of pathogenetic similarities in these renal disorders. Methods: The occurrence of IgA- and IgG anti-C1q antibodies (anti-C1q) were determined by ELISA in patients with IgA nephropathy (n=36) and SLE nephritis (n=37), diseases both known to be associated with circulating immune complexes. Levels of these antibodies were also determined in two other glomerular diseases, i.e. idiopathic membranous glomerulo-nephritis (n=7) and minimal change disease (n=2), in which circulating immune complexes are usually not present, and in 40 healthy controls. Results: IgA anti-C1q was observed in increased titres in 11/36 of the patients with IgA nephropathy, in 2/37 of the patients with SLE nephritis (both with proliferative disease) and in 1/9 of the patients with membranous and minimal change disease (P<0.001). Increased titres of IgG anti-C1q were observed in 1/36 of the patients with IgA nephropathy, in 17/37 of the patients with SLE nephritis and in 0/9 of the patients with membranous and minimal change disease (P<0.001). There were no correlations between the levels of anti-C1q antibodies and clinical parameters such as degree of proteinuria, haematuria, or renal function. Nor was there any correlation to the concentration of C3a and the terminal complement complex (TCC) in patients with IgA nephropathy. Conclusions: The occurrence of anti-C1q antibodies in both IgA nephropathy and SLE nephritis, albeit of different predominating isotypes, indicates the possibility of a similar pathogenic mechanism involved in these renal disorders. The occurrence of IgA anti-C1q antibodies in patients with IgA nephropathy has to our knowledge not previously been reported.     

Olfactory Absorption of Insulin to the Brain

A vast number of potent neuropharmaceuticals, many of which are peptides, are excluded from entry into the brain because of the highly selective blood-brain barrier. The fact that a number of drugs have been shown to be transported directly to the central nervous system following application to the olfactory region of the nose is therefore of major interest. In the present study, the feasibility of delivering peptides to the brain via the olfactory route was assessed using insulin as a model peptide. Systemic hyperinsulinemia induced by subcutaneous injection did not significantly reduce the amount of ¹²⁵I-insulin transported from the nose to the brain in vivo, which suggests that the impact of systemic absorption on drug transport is minimal. A linear relationship was seen between insulin accumulation in the brain and the dose applied, without any relevant saturation. Contrary to what was expected, both systemic and olfactory absorption of insulin was enhanced when the pH of the medium was near the isoelectric point. The amount absorbed to the brain was found to be linearly related to the net charge of the molecule (r = -0.61; n = 20). It was concluded that insulin gains access to the central nervous system from the olfactory region of the nose by a nonspecific pathway. The olfactory route may therefore become an important means to deliver peptides to the brain.     

Rising mortality from motor neurone disease in Sweden 1961–1990: the relative role of increased population life expectancy and environmental factors

Recent studies of mortality from motor neurone disease (MND) in Sweden have demonstrated rising levels of mortality from the disease, especially amongst older age groups. Case-control investigations have suggested that certain environmental factors are significantly related to variations in mortality from the disease, and are associated with a probable individual susceptibility to MND. This study applies an innovative epidemiological technique to longitudinal and cohort analysis of Swedish mortality from MND during the period 1961 to 1990. Survival modelling shows that a subpopulation susceptible to MND exists in Sweden, as has been demonstrated in other countries. The increased life expectancy of the Swedish population since 1961 has resulted in more of that susceptible population living to the ages at which MND is expressed, explaining the majority of the increase in mortality from the disease. However, environmental factors may play a role in accelerating the course of MND and may affect the timing of death within the susceptible sub-population.     

Periosteal transplantation to the rabbit patella

Autologous periosteal transplantation (without chondrocyte cell transplantation) for treating traumatic articular cartilage defects of the patella gives pain relief in uncontrolled clinical studies. To study the whole transplanted area macroscopically and microscopically, animal studies are motivated. In this pilot study, we reproduce the surgical technique for periosteum transplantation on human patella to a rabbit model. A full-thickness cartilage defect of the whole patella was created in eight adult female rabbits. The defect was treated with autologous periosteal transplantation. After surgery, the rabbits were allowed free activity. This is the difference compared to the treatment in humans, where our group uses CPM for 5 days and non-weight-bearing for 12 weeks. After 21 weeks, there was a diffuse synovitis in all transplanted knees, and in five of eight knees there were signs of osteoarthritis in the patello-femoral joint. Histologically, in three animals, small islands of hyaline cartilage surrounded by fibrocartilage were seen in the transplanted area. In the other five animals, fibrocartilage was the predominant tissue. In contrast to previous experimental studies using a rabbit model, we did not achieve hyaline cartilage resurfacing.     

Antimicrobial susceptibility testing of porcine Brachyspira (Serpulina) species isolates

No standardized method for susceptibility testing of Brachyspira spp. is currently available. A broth dilution procedure was evaluated and used to test the activities of six antimicrobial agents for 108 isolates of Swedish porcine Brachyspira spp. representing biochemical groups I, II, and III. Group I corresponds to Brachyspira hyodysenteriae, group II corresponds to B. intermedia, and group III corresponds to B. murdochii and B. innocens. A panel was designed with the antimicrobial agents dried in tissue culture trays with wells that allowed a liquid volume of 0.5 ml in each and agitation of the broth when incubated on a shaker. The MICs were determined by using brain heart infusion broth with 10% fetal calf serum. For 10 isolates, the results obtained in broth were compared to the MICs obtained on two different types of agar. Different inoculum densities and incubation times were also compared. The concentrations at which 90% of the B. hyodysenteriae isolates (n = 72) were inhibited in the broth dilution test by tiamulin (0.25 micro g/ml), tylosin (>256 micro g/ml), erythromycin (>256 micro g/ml), clindamycin (>4 micro g/ml), virginiamycin (4 micro g/ml), and carbadox (0.06 micro g/ml) were determined. The MICs tended to be lower in broth than on agar. Differences in inoculum densities and incubation times had little influence on the MICs. The evaluated broth dilution test was simple to perform, the end points were easily read, and the results were reproducible and reliable. No isolates with decreased susceptibility to tiamulin were found among the Swedish isolates tested.     

Improvements to a method for determining leg length following total hip arthroplasty

Abstract

Discrepancy in leg length does frequently occur as a side effect of total hip arthroplasty and may lead to reduced patient satisfaction as well as injury in the sequalae. It is consequently important to reduce leg length discrepancy where-ever technically possible. This may be achieved by recording precise intraoperative measurements and using different sized implanted components. The aim of the given study was to improve the accuracy of a previously validated optic measurement system (OMS) to reduce leg length discrepancy. This pre-existing OMS was first trialled and based on these preliminary findings developed further. Using this improved system, measurements were taken in models and cadavers. Inter observer reliability of the improved OMS was assessed. The system is introduced in the given technical feasibility study. Its accuracy was greater in the model setup (swivel joint: 772.7?±?1.5?mm; ball joint: 770.0?±?3.7?mm; reference: 772?mm) compared to the trial using cadaveric tissues (588.8?±?5.7?mm; reference: 586?mm). Results of two examiners were similar. The third one measured significantly shorter values (p=.011). The results of the measurements with the OMS indicate that a significant increase in accuracy (p?=?2.076×¹⁰?⁶) has been achieved compared to the previously reported system, however, a further improvement to measurement accuracy is necessary for this to be applied clinically.     

Does a torn anterior cruciate ligament lead to change in the central nervous drive of the knee extensors?

Summary Integrated surface electromyograms of the three superficial parts of the quadriceps and isokinetic knee extensor maximum torque and power production were recorded simultaneously and at different angular velocities in both legs in 11 male subjects with unilateral tear of the anterior cruciate ligament. The cross-sectional area (CSA) of the thigh and its muscular components were measured by computerized tomography. The principal findings were a small but significant decrease in quadriceps CSA on the affected side; a decreased active, but not passive, range of movement; decreased mechanical output, whether or not corrected for differences in CSA; and decreased electrornyographic activity — particularly in rectus femoris. These findings suggest that the reason for the decreased maximum and total knee extensor performance seen in these patients is a change in knee joint receptor afferent inflow.     

Expression of candidate tumor markers in ovarian carcinoma and benign ovary: evidence for a link between epithelial phenotype and neoplasia

EpCAM, epithelial membrane antigen (EMA)-mucin 1 (MUC1), mesothelin, and CD9 have been reported to be overexpressed at the RNA level in ovarian carcinomas. By using immunohistochemistry, we profiled the protein expression of these gene products in ovarian carcinoma tissues and compared them with benign ovarian surface epithelium (OSE) and cortical inclusion cysts (CICs). Immunoreactivity for EMA and calretinin were used to define epithelial and mesothelial differentiation in nontumor tissues, respectively. Papillary serous (n = 16) and endometrioid (n = 10) tumors were immunopositive for EMA/MUC1 (100%), mesothelin (75% and 30%, respectively), CD9 (88% and 90%, respectively), and EpCAM (100%). All ovarian carcinomas and carcinoma cell lines tested were negative for calretinin. In nonneoplastic ovary, both OSE and CICs ranged from flat-to-cuboidal to stratified and ciliated in appearance. OSE with a cuboidal morphology had a similar immunoreactivity as omental peritoneum, expressing calretinin, mesothelin, and CD9. In contrast, CICs with stratified and ciliated epithelium show expression patterns similar to those in fallopian tubes. They frequently expressed EMA, EpCAM, mesothelin, and CD9. This immunophenotype is preserved in ovarian carcinomas, suggesting that Müllerian metaplasia signals the acquisition of these markers and that their expression is maintained in ovarian carcinomas that originate from this epithelium.     

The R620W C/T polymorphism of the gene PTPN22 is associated with SLE independently of the association of PDCD1

The gene PTPN22 is located on chromosome 1p13 and encodes a protein tyrosine phosphatase called the lymphoid-specific phosphatase (Lyp). Lyp is expressed in lymphocytes, where it physically associates through its proline-rich motif (called P1) with the SH3 domain of the protein tyrosine kinase Csk, an important suppressor of the Src family of kinases Lck and Fyn, which mediate TCR signaling. Therefore, it is said that interaction between Lyp and Csk enables these effectors to inhibit T-cell activation synergistically. It was reported that a missense single nucleotide polymorphism , R620W (rs2476601), 1858C->T encodes an amino-acid change in the P1 proline-rich motif of the gene PTPN22 and is associated with SLE in North American white individuals. PTPN22 gene polymorphisms were genotyped in 571 Swedish SLE patients and 1042 healthy controls using TaqMan SNP Genotyping Assay. Differences were observed between cases and control subjects at both the allele (chi(2)=11.2895;P=0.0007,1df) and genotype (chi(2)=10.2243;P=0.0013, 1df) levels. We also found evidence of a genetic association between PTPN22 and renal disorder (chi(2)=9.5660;P=0.0019). We then analyzed if in patients with renal disorder associations with PDCD1 and PTPN22 were independent. Our data suggest that this appears to be the case although we observed some degree of interaction.     

Inflammation and the Association of Vitamin D and Depressive Symptomatology

Depression and vitamin D deficiency are major public health problems. The existing literature indicates the complex relationship between depression and vitamin D. The purpose of this study was to examine whether this relationship is moderated or mediated by inflammation. A community sample (n = 7162) from the LIFE-Adult-Study was investigated, for whom depressive symptoms were assessed via the German version of CES-D scale and serum 25-hydroxyvitamin D (25(OH)D) levels and inflammatory markers (IL-6 and CRP levels, WBC count) were quantified. Mediation analyses were performed using Hayes’ PROCESS macro and regression analyses were conducted to test moderation effects. There was a significant negative correlation between CES-D and 25(OH)D, and positive associations between inflammatory markers and CES-D scores. Only WBC partially mediated the association between 25(OH)D levels and depressive symptoms both in a simple mediation model (ab: −0.0042) and a model including covariates (ab: −0.0011). None of the inflammatory markers showed a moderation effect on the association between 25(OH)D levels and depressive symptoms. This present work highlighted the complex relationship between vitamin D, depressive symptoms and inflammation. Future studies are needed to examine the effect of vitamin D supplementation on inflammation and depressive symptomatology for causality assessment.