Comparison of surgical techniques for optimal lead placement in sacral neuromodulation: a cadaver study.

BACKGROUND: Sacral neuromodulation (SNM) is a common treatment for patients with urinary and faecal incontinence. A close contact of the tined lead electrode with the targeted nerve is likely to improve functional outcome. The aim of this study was to compare the position of the SNM lead in relation to the sacral nerve by comparing different implantation techniques. METHODS: This cadaver study was conducted at the Division of Anatomy of Vienna's Medical University in October 2020. We dissected 10 cadavers after bilateral SNM lead implantation (n = 20), using two different standardized implantation techniques. The cadavers were categorized as group A (n = 10), representing the conventional guided implantation group and group B (n = 10), where SNM implantation was conducted with the novel fluoroscopy-guided "H"-technique. The primary goal was to assess the distance between the sacral nerve and the lead placement. RESULTS: The electrodes were inserted at a median angle of 58.5° (46-65°) in group A and 60° (50-65°) in group B, without reaching statistical significance. In 8 cadavers, the lead entered the S3 foramen successfully. The median distance of the lead to the nerve did not show a significant difference between both groups (E0: Group A: 0.0 mm vs. Group B: 0.0 mm, p = 0.969; E1: Group A: 0.0 mm vs. Group B: 0.5 mm p = 0.754; E2: Group A: 2.5 mm vs. Group B: 2.5 mm p = 1.000; E3: Group A: 3.5 mm vs. Group B: 4.0 mm p = 0.675). In 2 cases (20%) of the conventional group A, the lead was misplaced and located at the gluteal muscle. Perforation of the presacral fascia was observed in one lead placement in group A and in two placements in group B. CONCLUSIONS: Both standardized implantation techniques may ensure close electrode proximity to the targeted nerve. Misplacement of the electrode was more often observed with the conventional implantation technique.

Standardized fluoroscopy-guided implantation technique enables optimal electrode placement in sacral neuromodulation: a cadaver study.

BACKGROUND: Sacral neuromodulation (SNM) is an established treatment option for patients with faecal incontinence. The location of the stimulating electrode is considered to be essential for treatment success. The purpose of this study was to evaluate the position of SNM electrodes after using a standardized fluoroscopy-guided implantation technique. METHODS: For this cadaver study, SNM electrodes were implanted bilaterally in 5 lower body specimens. The lower edge of the sacroiliac joint and the medial edge of the sacral foramina were marked using fluoroscopy to draw an 'H' with the crossing points identifying S3. After electrode placement the pelvis was dissected to describe the exact position of the SNM electrodes. RESULTS: The electrodes were inserted at an angle with a median degree measure of 60° (range 50-65°) to the skin, with a median distance of 9 mm (range 0-13 mm) from the S3 marking. All electrodes entered the third sacral foramen. The median distance of the electrodes to the sacral nerve was 0 mm (range 0-3 mm) for the most proximal, 0.5 mm (range 0-5 mm) for the second, 2.25 mm (range 0-11 mm) for the third and 1.75 mm (range 0-16 mm) for the most distant electrode. There was neither a significant difference in the proximity of the electrodes to the nerve between the right and left side (proximal to distal electrode: p = 0.18, p = 0.16, p = 0.07, p = 0.07) nor between male and female cadavers (p = 0.25, p = 0.21, p = 0.66, p = 0.66). CONCLUSIONS: A standardized fluoroscopy-guided implantation technique enables a close contact between electrode and nerve. This can potentially result in an improved clinical outcome.

Interconnected living in a quarter for persons with dementia.

OBJECTIVE: In this work, we propose a new care concept for dementia patients in their own apartments: interconnected living in a quarter. We describe a technical setup that is comprised of a safety system and an activity detection system. The latter detects, processes and illustrates activities of daily living to help the quarter managers to provide appropriate interventions for persons with dementia in the quarter. PARTICIPANTS: The nine-month field study reported in this work was conducted in two quarters with eight participants. METHODS: We evaluated different possibilities to determine activity indicators with the aim of providing information that enables the quarter managers to offer exactly the level of support needed by each individual patient. To evaluate the usefulness and the perception of the technical infrastructure, qualitative interviews with the dementia patients and the quarter managers were conducted. RESULTS: The results indicate that the interconnected living concept helps to increase the safety of the dementia patients. Additionally, several activity indicators that help the quarter managers to offer the appropriate level of support to the dementia patients have been identified. CONCLUSION: The presented concept, which has been evaluated in a real-world-setting, constitutes a new holistic and cross-disciplinary dementia care approach.

Placebo-controlled pilot study of the effects of an eggshell membrane-based supplement on mobility and serum biomarkers in dogs with osteoarthritis.

Osteoarthritis (OA) is a debilitating disease in dogs. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat OA; however, many dogs do not obtain adequate pain relief with an NSAID alone. This pilot study evaluated the systemic anti-inflammatory and mobility enhancing effects of an eggshell membrane-based nutritional supplement in dogs with OA-associated pain and mobility impairment. Twenty-seven dogs with OA-associated pain were enrolled into a randomized, double-masked, placebo-controlled, proof of principle pilot study and received either placebo or an eggshell membrane-based nutritional supplement over a 12-week period. Inflammatory biomarkers (IL-2, IL-6, IL-8, tumor necrosis factor-α, C-reactive protein, S100A12, and N-methylhistamine) were measured at Day 0 and Day 84. Owner questionnaires (CBPI and LOAD) were completed at Day 0, Day 42, and Day 84. Differences between groups over time were calculated. Twenty-two dogs completed the pilot study. Inflammatory biomarker IL-2 decreased in the supplement group, compared to the placebo group. Although small, the difference was statistically significant at an alpha of 0.1 (P=0.069). LOAD scores were numerically lower in the supplement group, but not significantly different from the placebo group at Day 0. Day 84 LOAD scores were significantly lower in the supplement group compared to the placebo group (P=0.034). CBPI results did not show the same pattern. The changes in biomarkers and LOAD scores were small, and do not provide definitive evidence of positive effects. However, these pilot results provide a rationale for performing a larger placebo-controlled study of the potential effects of the eggshell membrane-based nutritional supplement.

Extensor indicis proprius tendon transfer using shear wave elastography.

The means for judging optimal tension during tendon transfers are approximate and not very quantifiable. The purpose of this study was to demonstrate the feasibility of quantitatively assessing muscular mechanical properties intraoperatively using ultrasound elastography (shear wave elastography [SWE]) during extensor indicis proprius (EIP) transfer. We report two cases of EIP transfer for post-traumatic rupture of the extensor pollicis longus muscle. Ultrasound acquisitions measured the elasticity modulus of the EIP muscle at different stages: rest, active extension, active extension against resistance, EIP section, distal passive traction of the tendon, after tendon transfer at rest and then during active extension. A preliminary analysis was conducted of the distribution of values for this modulus at the various transfer steps. Different shear wave velocity and elasticity modulus values were observed at the various transfer steps. The tension applied during the transfer seemed close to the resting tension if a traditional protocol were followed. The elasticity modulus varied by a factor of 37 between the active extension against resistance step (565.1 kPa) and after the tendon section (15.3 kPa). The elasticity modulus values were distributed in the same way for each patient. The therapeutic benefit of SWE elastography was studied for the first time in tendon transfers. Quantitative data on the elasticity modulus during this test may make it an effective means of improving intraoperative adjustments.

Preclinical development of small-molecular-weight folate-based radioconjugates: a pharmacological perspective.

The folate receptor (FR) has attracted attention as a target structure because of its frequent expression in cancer cells (FR-α) and activated macrophages (FR-ß). The vitamin folic acid has served as a promising targeting ligand allowing selective delivery of attached radionuclides suitable for imaging of the diseased sites and for therapeutic application. A large number of folate radioconjugates with variable chemical structures have been developed over the last 25 years. Accumulation of radioactivity in healthy organs and tissues was always seen in the kidneys due to the expression of the FR in the proximal tubule cells. In some cases unspecific uptake of radiofolates was also seen in the liver and the intestinal tract. To address this situation and improve the target-to-off-target ratios of accumulated radioactivity several strategies were undertaken, including chemical modifications of the folate conjugates, selection of appropriate radionuclides and application of drug combinations. Depending on the radionuclide which was employed various chelators and linker entities were investigated and additional functionalities with albumin-binding properties were tested with the aim to increase the serum half-life of the radioconjugates. A number of diagnostic radionuclides ((99m)Tc, (111)In, (67)Ga, (155)Tb, (125)I) emitting γ-radiation were employed for single photon emission computed tomography (SPECT) and, ß(+)-emitting radionuclides ((68)Ga, 44Sc, (152)Tb, (18)F) were used for positron emission tomography (PET). Moreover, therapeutic radionuclides emitting ß(-)-particles ((177)Lu, (161)Tb, (47)Sc, (131)I) and α-particles ((149)Tb) were also used with folate conjugates. The present review focuses on the development of radiofolates and their in vivo properties and on strategies which were employed to modify their pharmacokinetic and pharmacodynamic properties.

[Therapeutic Drug Monitoring of antiinfectives in intensive care medicine]. / Therapeutisches Drug Monitoring (TDM) von Antiinfektiva in der Intensivmedizin.

Therapeutic Drug Monitoring (TDM) is based on drug-level control in biological matrices and serves as a diagnostic approach for individualization of pharmacotherapy and drug safety. Drug levels of antibiotics are distinctly influenced by comorbidity, physiological changes and various concomitant drugs in patients on intensive care units. Several factors should be taken into account for calculation of relevant pharmacokinetic parameters (elimination half-life, bioavailability, and clearance) to deduce a recommendation for dosage. TDM is a diagnostic standard for the individualization of polypharmcotherapy based on validated analytical methods (in particular LC-MS/MS and HPLC-methods) in order to optimize dosing and drug safety.

The cardioprotective effect of an aqueous extract of fermented rooibos (Aspalathus linearis) on cultured cardiomyocytes derived from diabetic rats.

Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle that contributes to cardiovascular deaths in the diabetic population. Excessive generation of free radicals has been directly implicated in the pathogenesis of DCM. The use of antioxidants, through dietary supplementation, to combat increased cellular oxidative stress has gained popularity worldwide. Aspalathus linearis (rooibos) is a popular herbal tea that contains a novel antioxidant, aspalathin. Literature has reported on the antidiabetic, anti-inflammatory and free radical scavenging effects of rooibos. However, its protective effect against DCM has not been established. Therefore, this study investigated whether chronic exposure to an aqueous extract of fermented rooibos (FRE) has an ex vivo cardioprotective effect on hearts obtained from streptozotocin (STZ) induced diabetic rats. Adult Wistar rats were injected with 40 mg/kg of STZ. Two weeks after STZ injection, cardiomyocytes were isolated and cultured. Cultured cardiomyocytes were treated with FRE (1 and 10 µg/ml), vitamin E (50 µg/ml), and n-acetyl cysteine (1mM) for 6h, before exposure to either hydrogen peroxide (H2O2) or an ischemic solution. Cardiomyocytes exposed to H2O2 or an ischemic solution showed a decrease in metabolic activity and glutathione content with a concomitant increase in apoptosis and intracellular reactive oxygen species. Pretreatment with FRE was able to combat these effects and the observed amelioration was better than the known antioxidant vitamin E. This study provides evidence that an aqueous extract of fermented rooibos protects cardiomyocytes, derived from diabetic rats, against experimentally induced oxidative stress and ischemia.

Comparative genetics of warfarin resistance.

Warfarin and other 4-hydroxycoumarin-based oral anticoagulants targeting vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) are administered to humans, mice and rats with different purposes in mind - to act as pesticides in high-dosage baits for killing rodents, but also to save lives when administered in low dosages as antithrombotic drugs in humans. However, high-dosage warfarin used to control rodent populations has resulted in numerous mutations causing warfarin resistance. Currently, six single missense mutations in mice, 12 distinct missense mutations in rats, as well as compound heterozygous or homozygous mutations with up to six distinct missense mutations per Vkorc1 allele have been described. Warfarin resistance missense mutations for human VKORC1 have also been found world-wide, but differ characteristically from those in rodents. In humans, 26 distinct mutations have been characterized, but occur only rarely either in heterozygous or, even rarer, in homozygous form. In this review, we summarize the known VKORC1 missense mutations causing warfarin and other 4-hydroxycoumarin drug resistance, identify genomics databases as new sources of data, explore possible underlying genetic mechanisms, and summarize similarities and differences between warfarin resistant VKORC1 variants in humans and rodents.

Amelioration of palmitate-induced insulin resistance in C2C12 muscle cells by rooibos (Aspalathus linearis).

Increased levels of free fatty acids (FFAs), specifically saturated free fatty acids such as palmitate are associated with insulin resistance of muscle, fat and liver. Skeletal muscle, responsible for up to 80% of the glucose disposal from the peripheral circulation, is particularly vulnerable to increased levels of saturated FFAs. Rooibos (Aspalathus linearis) and its unique dihydrochalcone C-glucoside, aspalathin, shown to reduce hyperglycemia in diabetic rats, could play a role in preventing or ameliorating the development of insulin resistance. This study aims to establish whether rooibos can ameliorate experimentally-induced insulin-resistance in C2C12 skeletal muscle cells. Palmitate-induced insulin resistant C2C12 cells were treated with an aspalathin-enriched green (unfermented) rooibos extract (GRE), previously shown for its blood glucose lowering effect in vitro and in vivo or an aqueous extract of fermented rooibos (FRE). Glucose uptake and mitochondrial activity were measured using 2-deoxy-[³H]-D-glucose, MTT and ATP assays, respectively. Expression of proteins relevant to glucose metabolism was analysed by Western blot. GRE contained higher levels of all compounds, except the enolic phenylpyruvic acid-2-O-glucoside and luteolin-7-O-glucoside. Both rooibos extracts increased glucose uptake, mitochondrial activity and ATP production. Compared to FRE, GRE was more effective at increasing glucose uptake and ATP production. At a mechanistic level both extracts down-regulated PKC θ activation, which is associated with palmitate-induced insulin resistance. Furthermore, the extracts increased activation of key regulatory proteins (AKT and AMPK) involved in insulin-dependent and non-insulin regulated signalling pathways. Protein levels of the glucose transporter (GLUT4) involved in glucose transport via these two pathways were also increased. This in vitro study therefore confirms that rooibos can ameliorate palmitate-induced insulin resistance in C2C12 skeletal muscle cells. Inhibition of PKC θ activation and increased activation of AMPK and AKT offer a plausible mechanistic explanation for this ameliorative effect.

Acute assessment of an aspalathin-enriched green rooibos (Aspalathus linearis) extract with hypoglycemic potential.

Rooibos, an endemic South African plant, known for its use as herbal tea, has potential as an antidiabetic herbal product, following recent demonstration of the glucose lowering effect of its major flavonoid, the dihydrochalcone C-glucoside aspalathin. The purpose of this study was to confirm antidiabetic activity for rooibos extract high in aspalathin content. An extract (SB1) was selected after screening for high aspalathin content and α-glucosidase inhibition activity. On-line HPLC-biochemical detection confirmed α-glucosidase inhibitory activity for aspalathin. In vitro the extract induced a dose response increase in glucose uptake (5 × 10⁻5 to 5 µg/ml) on C2C12 myotubules. Aspalathin was effective at 1, 10 and 100 µM, while rutin was effective at 100 µM. In the Chang cells only the extract was effective. In vivo the extract sustained a glucose lowering effect comparable to metformin over a 6h period after administration (25mg/kg body weight (BW)) to STZ-induced diabetic rats. In an oral glucose tolerance test the extract (30 mg/kg BW) was more effective than vildagliptin (10mg/kg BW), a dipeptidyl peptidase-4 inhibitor. An aspalathin-rutin mixture (1:1; m/m) dosed at 1.4 mg/kg BW, but not the single compounds separately, reduced blood glucose concentrations of STZ-induced diabetic rats over a 6h monitoring period. The improved hypoglycemic activity of the aspalathin-rutin mixture and the extract illustrated synergistic interactions of polyphenols in complex mixtures.

Antidiabetic, anti-oxidant and antimicrobial activities of Fadogia ancylantha extracts from Malawi.

ETHNOPHARMACOLOGICAL RELEVANCE: Communities in Chilumba, Malawi use herbal tea prepared from Fadogia ancylantha Schweinf (Rubiaceae) leaves for the management of diabetes, hypertension and alleviation of symptoms of gastrointestinal disorders and pneumonia. The objective of the study was to evaluate the in vitro antidiabetic, anti-oxidant and antimicrobial activities of the crude extracts of the leaves prepared by using three different extraction methods. MATERIALS AND METHODS: Each of the organic, cold and hot aqueous extracts of the herbal tea was evaluated for its effect on glucose uptake in C2C12 muscle and Chang cell lines. Metformin and insulin were used as positive controls. The anti-oxidant activity, based on neutralisation of DPPH free radicals, was determined spectrophotometrically. The Agar serial dilution method was utilised to determine the minimum inhibitory concentration (MIC) of the extracts for the selected fungal and bacterial strains. RESULTS AND DISCUSSION: The organic extract (12.5µg/ml) exhibited the highest in vitro glucose uptake increases in Chang cells (181.24±0.29%) and C2C12 muscle cells (172.29±0.32%) while the hot and cold aqueous extracts gave lower uptakes, 145.94±0.37% and 138.70±0.52% in Chang cells respectively. At 100µg/ml, aqueous extracts gave significantly higher (p<0.01) anti-oxidant activity (range 85.78-86.29%) than their organic counterpart (68.16%). The minimum inhibitory concentration (156µg/ml) was obtained in the organic extract against the fungus Aspergillus fumigatus and moderate growth inhibition was observed with other test micro-organisms. The hot aqueous extract inhibited the growth of all test organisms except Pseudomonas aeruginosa. The cold aqueous extract was inactive against Pseudomonas aeruginosa and Candida albicans. The differences in the MIC values between the aqueous extracts seem to suggest that raised temperatures, as traditionally practised, facilitate the extraction of secondary bioactive metabolites. CONCLUSION: These results show that Fadogia ancylantha extracts have high antidiabetic and anti-oxidant properties.

An in vitro assessment of the effect of Athrixia phylicoides DC. aqueous extract on glucose metabolism.

Athrixia phylicoides DC. is an aromatic shrub indigenous to the eastern parts of Southern Africa. Indigenous communities brew "bush tea" from dried twigs and leaves of A. phylicoides, which is consumed as a beverage and used for its medicinal properties. Plant polyphenols have been shown to be beneficial to Type 2 diabetes mellitus (T2D) and obesity. Aqueous extracts of the plant have been shown to be rich in polyphenols, in particular phenolic acids, which may enhance glucose uptake and metabolism. The aim of this study was to determine the phenolic composition of a hot water A. phylicoides extract and assess its in vitro effect on cellular glucose utilisation. The most abundant phenolic compounds in the extract were 6-hydroxyluteolin-7-O-glucoside, chlorogenic acid, protocatechuic acid, a di-caffeoylquinic acid and a methoxy-flavonol derivative. The extract increased glucose uptake in C2C12, Chang and 3T3-L1 cells, respectively. Intracellular glucose was utilised by both oxidation (C2C12 myocytes and Chang cells; p < 0.01 and p < 0.05, respectively) and by increased glycogen storage (Chang cells; p < 0.05). No cytotoxicity was observed in Chang cells at the concentrations tested. The effects of the extract were not dose-dependent. A. phylicoides aqueous extract stimulated in vitro glucose uptake and metabolism, suggesting that consumption of this phenolic-rich extract could potentially ameliorate metabolic disorders related to obesity and T2D.

Prevention of free fatty acid-induced lipid accumulation, oxidative stress, and cell death in primary hepatocyte cultures by a Gynostemma pentaphyllum extract.

Hepatocytes of a primary cell culture that are exposed to high glucose, insulin, and linoleic (LA) acid concentration respond with lipid accumulation, oxidative stress up to cell death. Such alterations are typically found in patients with non-alcoholic fatty liver disease (NAFLD). We used this cellular model to study the effect of an ethanolic Gynostemma pentaphyllum (GP) extract in NAFLD. When hepatocytes were cultured in the presence of high insulin, glucose, and LA concentration the extract completely protected the cells from cell death. In parallel, the extract prevented accumulation of triglycerides (TGs) and cholesterol as well as oxidative stress. Our data further demonstrate that GP stimulates the production of nitric oxide (NO) in hepatocytes and affects the molecular composition of the mitochondrial phospholipid cardiolipin (CL). We conclude that GP is able to protect hepatocytes from cell death, lipid accumulation, and oxidative stress caused by diabetic-like metabolism and lipotoxicity. Therefore, GP could be beneficial for patients with diabetes mellitus and NAFLD.

Prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND: Sorafenib is the new reference standard for patients with advanced hepatocellular carcinoma (HCC). AIM: To identify prognostic factors in sorafenib-treated HCC patients and to evaluate outcomes with respect to liver function. METHODS: In this retrospective study, 148 HCC patients received sorafenib 400 mg b.d. across 11 Austrian institutions. Seventy-eight HCC patients who received best supportive care (BSC) in the pre-sorafenib era served as a control. RESULTS: In sorafenib-treated patients, low baseline α-fetoprotein, low Child-Pugh (CP) score, compensated cirrhosis, and low baseline aspartate aminotransferase (AST) were associated with significantly longer overall survival (OS) on univariate analysis. CP score and baseline AST remained independent prognostic factors on multivariate analysis. In patients with Barcelona Clinic liver Cancer (BCLC) stage B or C HCC (sorafenib: n = 139; BSC: n = 39), CP-A patients had a median OS of 11.3 (sorafenib [n = 76]) vs. 6.4 (BSC [n = 17]) months (P = 0.010), and CP-B patients had a median OS of 5.5 (sorafenib [n = 55]) vs. 1.9 (BSC [n = 22]) months (P = 0.021). In the sorafenib group, median OS according to baseline AST was 11.8 (<100 U/L [n = 58]) vs. 3.9 (≥100 U/L [n = 15]) months for CP-A patients (P = 0.127), and 6.5 (<100 U/L [n = 33]) vs. 2.1 (≥100 U/L [n = 21]) months for CP-B patients (P = 0.011). There was no survival difference between sorafenib and BSC in patients with BCLC stage D HCC (1.5 vs. 1.4 months; P = 0.116). CONCLUSIONS: Sorafenib was associated with improved survival in both CP-A and CP-B patients. In CP-B patients, baseline AST may be helpful in determining which patients are most likely to benefit from sorafenib.

[Reticulated teleangiectatic erythema after implantation of medical devices. An increasingly occurring phenomenon?]. / Retikuläre teleangiektatische Erytheme nach Implantation von elektrischen medizinischen Geräten. Ein an Häufigkeit zunehmendes Phänomen?

Reticulated telangiectatic erythema (RTE) is a rare skin reaction to extraneous materials. We present three cases in which asymptomatic persistent erythemas developed in the area of implantation after medical devices were inserted. Topical and systemic treatment did not improve the skin changes. Patch testing including applied materials showed negative results in all cases. Histological investigation of punch biopsy specimens showed moderate dilatated vessels and a slight lymphocytic infiltrate. Due to our findings and in synopsis with the clinical impression we diagnosed RTE. As RTE is asymptomatic in most cases, the devices need not be removed.

[Strain experience and religiosity. A comparison of patients with chronic pain and breast cancer]. / Subjektive Belastung und Religiosität bei chronischen Schmerzen und Brustkrebs. Ein Stichprobenvergleich.

BACKGROUND: Studies show that especially ill people turn to their religious faith to find help in dealing with their diseases. However, religiousness is assumed to vary in its extent and effect depending on different kinds of strain. MATERIAL AND METHODS: In order to differentiate patterns of strain and coping, a sample of 178 patients with chronic pain was compared with 167 breast cancer patients. RESULTS: Pain patients show higher strain and impairment on almost all variables. Regression analyses indicate that patients with chronic pain are less religious in comparison to the breast cancer patients. CONCLUSIONS: Different values of the religious variables can be explained by different characteristics of the strain: Due to the threat to life experienced by the patients, the breast cancer group is more likely to turn to religiousness for help. Specific characteristics of chronic pain (e.g. longer illness duration, a stronger impairment in everyday activities) lead to higher resignation, also concerning religious efforts.

Vitamin D deficiency in patients with cutaneous lupus erythematosus is prevalent throughout the year.

BACKGROUND: Vitamin D mediates immunomodulatory functions and its deficiency has been associated with an increased prevalence of immunological diseases including systemic lupus erythematosus (SLE). Chronic discoid or subacute cutaneous lupus erythematosus (CLE) are ultraviolet (UV)-triggered skin diseases. As vitamin D is mostly UV-derived and not from nutrition, its deficiency is frequent especially during the UV-deprived winter months. OBJECTIVE: To compare the vitamin D status of patients with CLE with patients with type I allergy and healthy individuals during the summer or winter months. METHODS: The vitamin D status of patients with CLE (n = 41) was compared with patients with type I allergy (n = 24), healthy individuals (n = 25) and a reference pool (n = 1951) by means of concentrations of circulating storage metabolite 25-hydroxyvitamin D in the summer and winter. RESULTS: Serum 25-hydroxyvitamin D concentrations were lower during the winter in the reference population, and type I allergic and healthy individuals (29.2­35.5 nmol L)1) compared with the summer months (56.3­89.8 nmol L)1) and paralleled by the prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D< 50 nmol L)1; winter: 70.8­73.4%, summer: 34.9­39.4%). In contrast, vitamin D deficiency in patients with CLE was prevalent throughout the year (summer: 85.7%,winter: 97.1%). In patients with CLE with concomitant prednisolone treatment, the 25-hydroxyvitamin D serum levels were comparable with (mean daily intake 877 IU) or without vitamin D supplementation during summer or winter (P = 0.75 and P = 0.14, respectively). CONCLUSIONS: Our data identify vitamin D deficiency in patients with CLE throughout the year and indicate that monitoring and correcting the vitamin D status should be considered to prevent bone demineralization and fractures and to modulate beneficially immunological dysfunction.

Development of glucose intolerance in Wistar rats fed low and moderate fat diets differing in fatty acid profile.

BACKGROUND/AIMS: Both dietary fat content and fatty acid composition play a role in the development of glucose intolerance and insulin resistance. In this study we investigated the effect of moderate increases in dietary fat (10-30% of fat as total calories) and associated differences in fatty acid content, on the development of metabolic perturbations in the Wistar rat. METHODS: Eighteen normal male Wistar rats were randomly divided into 3 groups (n=6 each) at weaning, and fed different diets for 10 months: D10-10% fat as energy; D20-20% fat as energy and D30-30% fat as energy ad libitum. RESULTS: Compared with D10, rats fed D20 and D30 exhibited increased body weight from as early as 1 month of the study (p<0.01). None of the diets resulted in hyperglycemia, but glucose intolerance developed as early as 1 month in the D20 and D30 groups (p<0.01) following intravenous glucose tolerance test. Over time, the glucose stimulated insulin secretion rate (GSIS) became more blunted in the D20 and D30 groups, but by 10 months the D20 group regained some insulin responsiveness. D30 showed very poor GSIS at 10 months indicating glucose intolerance. Plasma omega6 and omega3 fatty acid profiles mostly reflected the dietary content, but the ratio of omega6:omega3 in plasma deteriorated over time in D30, whereas that of D10 and D20 improved. CONCLUSION: A moderate increase in dietary fat (20%), within the recommended nutritional range, and an unfavourable omega6:omega3 ratio resulted in glucose intolerance in this Wistar rat model, which was exacerbated with a further increase in dietary fat (30%).