Maria Wallin

Cadmium, mercury, and lead in kidney cortex of living kidney donors: Impact of different exposure sources.

BACKGROUND Most current knowledge on kidney concentrations of nephrotoxic metals like cadmium (Cd), mercury (Hg), or lead (Pb) comes from autopsy studies. Assessment of metal concentrations in kidney biopsies from living subjects can be combined with information about exposure sources like smoking, diet, and occupation supplied by the biopsied subjects themselves. OBJECTIVES To determine kidney concentrations of Cd, Hg, and Pb in living kidney donors, and assess associations with common exposure sources and background factors. METHODS Metal concentrations were determined in 109 living kidney donors aged 24-70 years (median 51), using inductively coupled plasma-mass spectrometry (Cd and Pb) and cold vapor atomic fluorescence spectrometry (Hg). Smoking habits, occupation, dental amalgam, fish consumption, and iron stores were evaluated. RESULTS The median kidney concentrations were 12.9microg/g (wet weight) for cadmium, 0.21microg/g for mercury, and 0.08microg/g for lead. Kidney Cd increased by 3.9microg/g for a 10 year increase in age, and by 3.7microg/g for an extra 10 pack-years of smoking. Levels in non-smokers were similar to those found in the 1970s. Low iron stores (low serum ferritin) in women increased kidney Cd by 4.5microg/g. Kidney Hg increased by 6% for every additional amalgam surface, but was not associated with fish consumption. Lead was unaffected by the background factors surveyed. CONCLUSIONS In Sweden, kidney Cd levels have decreased due to less smoking, while the impact of diet seems unchanged. Dental amalgam is the main determinant of kidney Hg. Kidney Pb levels are very low due to decreased exposure.

Low-level cadmium exposure and effects on kidney function

Objectives The nephrotoxicity of cadmium at low levels of exposure, measured by urinary cadmium, has recently been questioned since co-excretion of cadmium and proteins may have causes other than cadmium toxicity. The aim of this study was to explore the relation between kidney function and low or moderate cadmium levels, measured directly in kidney biopsies. Methods We analysed cadmium in kidney biopsies (K-Cd), blood (B-Cd) and urine (U-Cd) from 109 living kidney donors in a cross-sectional study. We measured glomerular filtration rate (GFR), cystatin C in serum, albumin, β-2-microglobulin (B2M), retinol-binding protein (RBP), α-1-microglobulin (A1M), N-acetyl-β-d-glucosaminidase and kidney injury molecule 1 (KIM-1) in 24 h and overnight urine. Results We found significant positive associations between A1M excretion and K-Cd in multiple regression models including age, sex, weight, smoking and urinary flow rate. This association was also present in never-smokers. A1M was also positively associated with B-Cd and U-Cd. GFR and the other biomarkers of kidney function were not associated with K-Cd. GFR estimated from serum cystatin C showed a very poor correlation with measured GFR. KIM-1, RBP and possibly albumin were positively associated with U-Cd, but only in overnight urine. No associations were found with B2M. Conclusions Our results suggest that A1M in urine is a sensitive biomarker for effects of low-level cadmium exposure. A few associations between other renal biomarkers and U-Cd, but not K-Cd, were probably caused by physiological co-excretion or chance.

Low-Level Cadmium Exposure Is Associated With Decreased Bone Mineral Density and Increased Risk of Incident Fractures in Elderly Men: The MrOS Sweden Study.

One risk factor for osteoporosis that has attracted increasing attention in recent years is exposure to cadmium. The aim of this study was to examine the associations between low‐level cadmium exposure, from diet and smoking, and bone mineral density (BMD) and incident fractures in elderly men. The study population consisted of 936 men from the Swedish cohort of the Osteoporotic Fractures in Men (MrOS) study, aged 70 to 81 years at inclusion (years 2002 to 2004), with reliable data on cadmium in urine (U‐Cd) analyzed using inductively coupled plasma mass spectrometry in baseline samples. The participants also answered a questionnaire on lifestyle factors and medical history. BMD was measured at baseline using dual‐energy X‐ray absorptiometry (DXA) in the total body, hip, and lumbar spine. During the follow‐up period (until 2013), all new fractures were registered by date and type. Associations between BMD and U‐Cd were assessed using multiple linear regression, and associations between incident fractures and baseline U‐Cd were analyzed using Cox regression. In both cases, a number of potential confounders and other risk factors (eg, age, smoking, body mass index [BMI], and physical activity) were included in the models. We found significant negative associations between U‐Cd and BMD, with lower BMD (4% to 8%) for all sites in the fourth quartile of U‐Cd, using the first quartile as the reference. In addition, we found positive associations between U‐Cd and incident fractures, especially nonvertebral osteoporosis fractures in the fourth quartile of U‐Cd, with hazard ratios of 1.8 to 3.3 in the various models. U‐Cd as a continuous variable was significantly associated with nonvertebral osteoporosis fractures (adjusted hazard ratio 1.3 to 1.4 per μg Cd/g creatinine), also in never‐smokers, but not with the other fracture groups (all fractures, hip fractures, vertebral fractures, and other fractures). Our results indicate that even relatively low cadmium exposure through diet and smoking increases the risk of low BMD and osteoporosis‐related fractures in elderly men.

Charged microcapsules for controlled release of hydrophobic actives Part II: Surface modification by LbL adsorption and lipid bilayer formation on properly anchored dispersant layers

Charge microcapsules with a dodecane core and a poly(methyl methacrylate) (PMMA) shell have been prepared via the internal phase separation method using ionic dispersants. The microcapsules have subsequently been surface modified with polyelectrolyte multilayers and lipid bilayers. Two types of ionic dispersant systems have been investigated: a small set of ionic amphiphilic block copolymers of poly(methyl methacrylate)-block-poly(sodium (meth)acrylate) type and an oil-soluble anionic surfactant, sodium 1,5-dioxo-1,5-bis(3,5,5-trimethylhexyloxy)-3-((3,5,5trimethylhexyloxy)carbonyl)pentane-2-sulfonate, in combination with a water-soluble polycation, poly(diallyldimethylammonium chloride). The Layer-by-Layer adsorption of the polyelectrolyte pair poly(diallydimethylammonium chloride) (350,000 g/mol) and poly(sodium methacrylate) (15,000 g/mol) was successfully made on both microcapsule systems with the formation of very thin multilayers as indicated with quartz crystal microbalance with dissipation monitoring (QCM-D) measurements on model surfaces. Formation of a lipid bilayer on the surface of the microcapsules from liposomes with a charge opposite that of the capsule surface was also proven to be successful as indicated by the ζ-potential of the microcapsules, the characteristic frequency shift as measured with QCM-D and fluorescence recovery after photobleaching (FRAP) on model systems. However, the proper anchorage of the dispersants in the underlying PMMA surface was key for the successful surface modification.

Incidence of cutaneous melanoma in Western Sweden, 1970-2007.

The aim of this study was to describe the increasing incidence of cutaneous malignant melanoma (CMM) in Western Sweden during the period 1970–2007. A secondary aim was to show a geographical variation in incidence between coastal and inland areas, considering the effects of the local average duration of sunshine, and the sun exposure-related behavior in the populations. The Swedish Cancer Registry provided data on invasive melanomas during 1970–2007. Meteorological maps showed the annual average duration of sunshine during 1961–1990. A survey from 2007 with 2871 participants, carried out by the National Board of Health and Welfare, provided data on self-reported sun exposure. During the period studied, the age-standardized incidence for men in Western Sweden more than quadrupled to 31.1/100 000 inhabitants, whereas it tripled for women to 27.1/100 000. Coastal areas, including Gothenburg city, had a high average duration of sunshine (1701–1900 h of sun/year), whereas inland areas had lower average duration of sunshine (⩽1700 h). The incidence of CMM was higher in coastal areas and in Gothenburg city, compared with inland areas. This may be linked to ultraviolet radiation, a consequence of the higher average duration of sunshine. The sun exposure survey showed additional factors, which possibly led to the increased incidence, for example high sun exposure on holidays abroad. The alarming increase in the incidence of CMM in Western Sweden, during the period 1970–2007, shows the need for additional primary preventive measures, for example sun protection programs targeted at populations in this area.

Meso-Ordered PEG-Based Particles

We report on the formation of meso-ordered hydrogel particles by cross-linking poly(ethylene glycol) diacrylate (PEG-DA) in the presence of surfactants in a confined environment. The results demonstrated that well-ordered mesoporous hydrogel particles having a pore size of about 5 nm could be formed. It is suggested that these meso-ordered hydrogel particles might have unique drug-delivery capabilities.

Response to "Low-Level Cadmium Exposure and Bone Health".

Maria Wallin, Lars Barregard, Gerd Sallsten, Thomas Lundh, Magnus K Karlsson, Mattias Lorentzon, Claes Ohlsson, and Dan Mellstr€ om Department of Occupational and Environmental Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, and Sahlgrenska University Hospital, Gothenburg, Sweden Department of Occupational and Environmental Medicine, Skåne University Hospital, Lund, Sweden Departments of Orthopedics and Clinical Sciences, Lund University, Skåne University Hospital, Malm€ o, Sweden Centre for Bone and Arthritis Research (CBAR), Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Department of Geriatric Medicine, Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Quantitative and semi-quantitative histopathological examination of renal biopsies in healthy individuals, and associations with kidney function

This study assesed the prevalence of histopathological changes in renal biopsies from healthy individuals, and the association with age, sex and smoking. Donor biopsies from 109 subjects were obtained from living kidney donors, and blood and urine samples were collected together with medical history. All biopsies were scored according to the Banff ‘97 classification with some modifications. The parameters included in this study were tubular atrophy, interstitial fibrosis, glomerulosclerosis, arteriosclerosis, arteriolohyalinosis and a sclerosis score. An alternative scoring system for tubular atrophy was examined (using ≤5% rather than <1% as a cut‐off for grade 0). Glomerular filtration rate was measured in most cases as chromium ethylenediaminetetra‐acetic acid (Cr‐EDTA) clearance. Age was a significant predictor for tubular atrophy, fibrosis and sclerosis. Pack‐years of smoking increased the risk of tubular atrophy, fibrosis and arteriolohyalinosis. The alternative scoring of tubular atrophy showed a stronger association with smoking, but a weaker association with age, compared with the original one. Limited histopathological changes are common in healthy kidney donors around 50 years of age with normal kidney function. We propose that a cut‐off of ≤5% yields a better definition of grade 0 tubular atrophy compared with the established cut‐off of >0%.

Neuropsychological effects of shunting in iNPH – determining major and minor responses

iNPH is characterized by a wide range of neuropsychological deficits. The severity of impairment is associated with that of gait, balance and continence disturbances, and correlations between results on disparate neuropsychological tests are far stronger than among healthy; a dedifferentiation of functions. Following surgery, performance at group level, is significantly improved and remains stable for at least the first year of treatment. Importantly, however, shunted iNPH patients still perform well below normal levels. The magnitude of change varies substantially, some patients showing only modest advances or even further deterioration, whereas others show considerable improvements on the majority or all administered tests. In this study we compared patients belonging to these two extremes, aiming to predict neuropsychological benefits of surgery.

Predicting neuropsychological outcome following shunt operation in iNPH using reliable change indices (RCIs).

While most iNPH patients experience a change in neuropsychological functioning after shunt operation there is a considerable variation in the extent, direction and nature of change. In this study we examined preoperative characteristics and their relationship to neuropsychological preoperative functioning and postoperative change. To determine neuropsychological change, reliable change indices (RCIs) were used. RCIs have been used to identify cognitive changes in other populations such as epilepsy, Parkinsons disease, dementia and sports medicine but have never previously been used in iNPH research. The aim of the study was to aid patients and healthcare professionals to make informed decisions regarding surgery and to introduce the use of RCIs to establish change after shunting.