Low brain-derived neurotrophic factor protein levels and single-nucleotide polymorphism Val66Met are associated with peripheral neuropathy in type II diabetic patients.

BACKGROUND: Studies by our group demonstrated brain-derived neurotrophic factor (BDNF) levels in blood and BDNF-Val66met-SNP as potential biomarkers in chemotherapy-induced peripheral neuropathy. Here, we evaluate symptoms of peripheral neuropathy (PN) and depression in patients with type II diabetes mellitus in search of an association with serum BDNF levels and the Val66Met-SNP. METHODS: In total, 90 patients enrolled in the study; 23 (25.6%) had known PN, as determined by nerve conduction studies (NCS-PN), and 67 (74.4%) were not diagnosed with PN (U-PN). PN symptoms were assessed and graded in these groups using the total neuropathy score (TNSr) and DN4 scales. Small nerve fiber testing of sensitivity thresholds to cold, warm and hot pain signals was performed using the Q-sense device. Depression was assessed using the PHQ9 questionnaire. BDNF protein levels and Val66Met-SNP were determined with ELISA and Sanger sequencing, respectively. RESULTS: NCS-PN patients showed lower serum BDNF levels alongside significantly higher TNSr, DN4 and PHQ9 scores and lower hot pain sensitivity thresholds as compared to U-PN patients. Patients with Met-BDNF-SNP showed increased TNSr scores and lower hot pain sensitivity thresholds as compared to patients with Val-BDNF-SNP. Depression showed a weaker correlation with sensitivity thresholds to hot pain signals as compared to TNSr and DN4 scores. CONCLUSIONS: Diminished peripheral BDNF resources and Met-BDNF-SNP genotype are associated with augmented symptoms of PN in patients with type II diabetes mellitus. Sensitivity thresholds to hot pain signals may be less influenced by depression and possibly more accurately detect PN symptoms in diabetic patients.

Is routine measurement of TSH in hospitalized patients necessary?

TSH routine testing in hospitalized patients has low efficacy, but may be beneficial in a selected subgroup of patients. Our aim was to evaluate the efficacy of routine thyroid function tests among patients admitted to internal medicine departments. It is a retrospective study. A randomly selected cohort of hospitalized patients with abnormal thyroid-stimulating hormone (TSH) blood tests drawn as part of admission protocol. Patient data were collected from the electronic medical files and analyzed for its efficacy. TSH as a screening test was proven unnecessary in 75% (174) of the study population. Leading causes were non-thyroidal illness syndrome, drugs affecting the test results and subclinical disorders. TSH testing was found to be clinically helpful in only 9 patients; however, all of them had other clinical need for TSH testing. We found a clinically abnormal TSH in 20 patients, hypothyroidism in 11 patients and thyrotoxicosis in 9 patients. Low efficacy ascribed to TSH screening test by this study correlates with recent recommendations that indicate TSH screening in admitted patients only with accompanying clinical suspicion. Most probably, the majority of patients found by screening to have thyrotoxicosis have non-thyroidal illness or drug effects so the threshold for FT4 to diagnose overt thyrotoxicosis should be higher than that in ambulatory patients. In elderly patients, clinically relevant TSH disturbances are more frequent and are harder to diagnose, therefore, TSH screening in this group of patients might be beneficial.

[THE CLINICAL APPROACH TO DIAGNOSIS AND TREATMENT OF HYPOTHYROIDISM].

INTRODUCTION: Hypothyroidism is the most frequent endocrinologic disorder after diabetes. It is caused by the insufficient production of thyroid hormones Thyroxine (T4) and Triiodothyronine (T3). T4 is the main hormone that is accumulated in the thyroid gland, while T3 is the active hormone that is produced from T4 in the peripheral tissues. More than 99% of the patients have primary hypothyroidism which is due to thyroid disorder mainly Hashimoto's thyroiditis or iatrogenic. Hypothyroidism is divided into sub-clinical when T4 is in the normal range and overt when it is low and usually the TSH level is higher than 10 mIU\L. The diagnosis is based on blood tests, because the signs and symptoms are neither specific nor sensitive. In the elderly, the upper limit of normal TSH level is higher than that reported by the laboratory in Israel and in healthy young it is lower. TSH is the most sensitive tool for screening, diagnosis and treatment follow-up when the pituitary is normal. The drug of choice in hypothyroidism is Levothyroxine (T4 salt) which is very effective, well tolerated and inexpensive.

Stability and bioavailability of vitamin D nanoencapsulated in casein micelles.

We have previously introduced the potential of casein micelles (CM) as natural nanovehicles for hydrophobic nutraceuticals, e.g. vitamin D (VD) (E. Semo, E. Kesselman, D. Danino and Y. D. Livney, Food Hydrocolloids, 2007, 21, 936-942). The aims of the current study were to improve performance by adding an ultra-high-pressure homogenization step, and to evaluate the protection conferred by re-assembled CM (rCM) against VD thermal and oxidative degradation, and the bioavailability of VD(3) in rCM, by a clinical trial. Dynamic-light-scattering showed that VD(3)-rCM had a diameter of 91 ± 8 nm (average ± standard error). When VD(3) was encapsulated in rCM and subjected to thermal treatment (80 °C, 1 min), no significant loss was observed (P > 0.05), compared to 13 and 14% loss of VD(3) emulsified with Tween-80 (a synthetic emulsifier typically used for VD solubilization) and of unencapsulated VD(3) respectively (P < 0.05). VD(3) in rCM was also more stable during 28 d cold storage (∼40% loss) compared to Tween-80 emulsified (∼50% loss) or to un-encapsulated (∼70% loss) VD(3). Ultra-high-pressure homogenization of VD(3)-rCM (∼155 MPa) significantly enhanced vitamin stability, resulting in only ∼10% loss after 28 d of storage. Bioavailability of a single-dose of 50,000 international-units (IU) VD(3) encapsulated in rCM, in 1% fat milk, investigated in a randomized double blinded placebo controlled clinical study with 87 human volunteers, was at least as high as that using an aqueous Tween-80-emulsified VD(3) supplement. We conclude that ultra-high-pressure homogenization treated rCM protect VD(3) against heat- and storage-induced degradation, and VD(3) encapsulated in rCM is highly bioavailable.