Association between multiple sclerosis and urinary levels of toxic metals and organophosphates: A cross-sectional study in Israel.

BACKGROUND: Multiple sclerosis (MS) is a multifactorial disease of uncertain etiology damaging myelin sheaths around axons of the central nervous system. Myelin protects the axon from potentially harmful exogenous factors. The aetiological role of environmental exposure metals and organophosphates is unclear. OBJECTIVE: Identify whether urinary levels of metals and organophosphates differed in MS patients and controls. METHODS: We recruited MS patients from Ziv Medical Centre and healthy controls. MS patients were evaluated according to Expanded Disability Status Scale into mild and moderate-severe conditions. Each participant provided a urine sample and completed epidemiological questionnaires. The levels of six metal (Aluminum, Cadmium, Chromium, Lead, Mercury, Nickel) and one metalloid (Arsenic) and common organophosphates pesticide metabolites (6 dialkylphosphates, DAP) were measured in urine using inductively coupled plasma-mass spectrometry and gas-chromatography mass-spectrometry. We compared cases with controls in terms of urinary levels of these compounds using Mann-Whitney and Kruskall-Wallis tests. RESULTS: Urinary cadmium and mercury levels were higher in the 49 MS patients than the 37 controls (p < 0.01). Cadmium levels were higher in moderate-severe MS patients (n = 24) than mild MS patients (n = 25) (p = 0.003). CONCLUSION: Urinary cadmium and mercury levels were higher among MS patients than controls. Cadmium levels correlated with disease severity. Further studies are needed to explore potential causal pathways between these compounds and MS pathogenesis.

Effects of hemodialysis with cooled dialysate on high-sensitivity cardiac troponin I and brain natriuretic peptide.

BACKGROUND: Hemodialysis (HD) triggers recurrent and cumulative ischemic insults to the brain and the heart. Cooled dialysate may have a protective effect on major organs and improve hemodynamic tolerability of dialysis. The aim of the study was to compare HD with cooled dialysate with routine dialysis in terms of hemodynamic stability and levels of high-sensitivity Troponin I (hs-TnI) and N-terminal pro b-type natriuretic peptide (NTproBNP) pre and postdialysis. METHODS: The 45 patients were randomized into two groups. The first group received a 35.5°C dialysate first (hypothermic dialysis) and the second group a 36.5°C dialysate first (routine dialysis). Then groups crossed over, so each group received the alternate dialysate (self-controls) For each patient, the first sample was collected at the beginning of dialysis, and a second sample was taken at the end of dialysis. RESULTS AND CONCLUSION: hs-TnI and NTproBNP increased after routine HD by 10.7 ng\ml (p < 0.001) and (12.0 pg/µl) (p < 0.001), respectively, and by -3.1 ng\ml (p = 0.25) and (4.3 pg/µl) (p < 0.001), respectively after hypothermic HD. Our study results showed a tendency towards less rise in hsTnI and NTproBNP during hypothermic HD (35.5°C) as compared to routine HD (36.5°C). Neither arm experienced statistically significant changes in blood pressure. Further studies in larger cohorts and long follow up are warranted in order to confirm that lower rise in (hs-TnI) and NTproBNP actually translate into lower clinical risk for cardiovascular events.

Does Routine Sedation Influence Anxiety and CRP levels in Patients Undergoing Elective Coronary Catheterization?

BACKGROUND: Cardiac catheterization is associated with patient anxiety. Benzodiazepines are often used to relieve anxiety in this setting. The association between anxiety level and C-reactive protein (CRP) remains equivocal. We sought to determine whether anxiety and CRP levels in patients undergoing elective left heart catheterization differ when routine sedation with midazolam is administered. METHODS: Patients undergoing elective left heart catheterization were randomly assigned to receive 2 mg of midazolam intravenously or placebo before access insertion in a double-blinded manner. Levels of anxiety were assessed using the State-Trait Anxiety Inventory for Adults (short form) and high-sensitivity CRP at the time of admission and discharge. Surrogate markers for anxiety, such as blood pressure and pulse, were recorded before and after the procedure. Patient-perceived discomfort was measured with a visual analog scale (VAS) on a 0-10 scale. RESULTS: One hundred patients (52 receiving treatment, 48 receiving placebo) participated in the study. Baseline demographic characteristics and previous medical conditions were well balanced between groups. Anxiety level, systolic blood pressure, and diastolic blood pressure were all higher at procedure start than post procedure, but did not differ between the groups. CRP levels were similar at both time points for patients in both groups (0.77 ± 2.53 mg/L pre procedure and 0.70 ± 2.08 mg/L post procedure in the midazolam group vs 0.79 ± 1.39 mg/L pre procedure and 0.83 ± 1.45 mg/L post procedure in the placebo group). Discomfort level assessment was also alike (2.6 ± 2.4 in the treatment group vs 3.4 ± 2.5 in the placebo group; P=.12). CONCLUSIONS: Intravenous midazolam administration does not seem to relieve patient discomfort and anxiety nor does it influence CRP level. Therefore, an approach tailored to the patient is advisable.

Is the probable spillage of the lung surfactant dipalmitoylphosphatidylcholine the ultimate source of diabetes type 1?

The lung surfactant dipalmitoylphosphatidylcholine (DPPC) most probably leaks into the blood, settling on the luminal aspect of blood vessels to create active hydrophobic spots (AHS). Nanobubbles are formed at these spots from dissolved gas. We hypothesized that when a large molecule in the blood comes into contact with a nanobubble at the AHS, its tertiary structure is disrupted. An epitope not previously having undergone thymus education may then prompt an autoimmune response. There are thus two independent processes which may share the blame for autoimmune disease: spillage of large molecules into the blood, and the creation of AHS. DPPC was measured in 10 diabetes type 1 patients and 10 control subjects. DPPC in the diabetic group was 4.63 ± 0.68 µg/mL, non-significantly higher than in the control group (4.23 ± 0.94 µg/mL). However, in the diabetic group, DPPC was high when the samples were taken within 1.5 years of disease onset. This is closer to the time of AHS production, which takes place ahead of the disease. Further investigation, with sampling for DPPC as soon as possible after onset of the disease, may provide additional support for our hypothesis. If proved true, this may open up considerable therapeutic potential.

A comparative study of reproductive and metabolic responses to administration of exogenous melatonin and aldosterone in xeric and mesic spiny mice populations.

A comparative study of reproduction revealed differences between desert-adapted Acomys russatus and Mediterranean Acomys cahirinus populations with respect to the environmental cues used for reproductive activity. Long day (LD) conditions were noted as initial reproductive cue for both populations. This research is a follow-up affects comparative endocrine and metabolic study in regards to reproduction where LD-acclimated mice were treated with, exogenous aldosterone (ALDO) and melatonin (MLT). Only the reproductive system of A. russatus females was significantly affected by both hormones. In A. cahirinus females, MLT decreased leptin levels, while in A. russatus, a treatment with both hormones increased leptin levels. In A. russatus males, MLT affects both reproductive and metabolic functions. However, in A. cahirinus males, ALDO and MLT treatments caused an increase in leptin levels, and a decrease in free fatty acid (FFA) levels, respectively. Correlations between leptin and FFA in general were affected by both MLT and ALDO treatments in A. russatus males and A. cahirinus females. Our results support the general idea, that although the reproductive system of A. russatus responded to an osmotic stress, in our case expressed by ALDO treatment, which can be considered as an ultimate signal, where, photoperiod changes are an initial signal.

Reproductive and metabolic responses of desert adapted common spiny male mice (Acomys cahirinus) to vasopressin treatment.

Sufficient amounts of water and food are important cues for reproduction in an unpredictable environment. We previously demonstrated that increased osmolarity levels, or exogenous vasopressin (VP) treatment halt reproduction of desert adapted golden spiny mice Acomys russatus. In this research we studied gonad regulation by VP and food restriction (FR) in desert adapted common spiny mouse (A. cahirinus) males, kept under two different photoperiod regimes-short (SD-8L:16D) and long (LD-16L:8D) days. Mice were treated with VP, FR, and VP+FR for three weeks. Response was assessed from changes in relative testis mass, serum testosterone levels and mRNA receptor gene expression of VP, aldosterone and leptin in treated groups, compared with their controls. SD-acclimation increased testosterone levels, VP treatment decreased expression of aldosterone mRNA receptor in the testes of SD-acclimated males. FR under SD-conditions resulted in testosterone decrease and elevation of VP- receptor gene expression in testes. Aldosterone receptor mRNA expression was also detected in WAT. These results support the idea that water and food availability in the habitat may be used as signals for activating the reproductive system through direct effects of VP, aldosterone and leptin on the testes or through WAT by indirect effects.

Photoperiodicity and increasing salinity as environmental cues for reproduction in desert adapted rodents.

Understanding the ways environmental signals, regulate reproduction and reproductive behavior of desert adapted rodents is a major gap in our knowledge. In this study, we assessed the roles of photoperiod and diet salinity, as signals for reproduction. We challenged desert adapted common spiny mice, Acomys cahirinus, males and females with osmotic stress, by gradually increasing salinity in their water source - from 0.9% to 5% NaCl under short and long days (SD and LD, respectively). Photoperiodicity affected testosterone levels, as under LD-acclimation, levels were significantly (p<0.05) higher than under SD-acclimation. Salinity treatment (ST) significantly reduced SD-acclimated male body mass (W(b)) and testis mass (p<0.005; normalized to W(b)). ST-LD-females significantly (p<0.005) decreased progesterone levels and the numbers of estrous cycles. A reduction in white adipose tissue (WAT) to an undetectable level was noted in ST-mice of both sexes under both photoperiod regimes. Receptors for vasopressin (VP) and aldosterone were revealed on testes of all male groups and on WAT in control groups. Our results suggest that photoperiod serves as an initial signal while water availability, expressed by increased salinity in the water source, is an ultimate cue for regulation of reproduction, in both sexes of desert-adapted A. cahirinus. We assume that environmental changes also affect behavior, as water seeking behavior by selecting food items, or locomotor activity may change in extreme environment, and thus indirectly affect reproduction and reproductive behavior. The existence of VP and aldosterone receptors in the gonads and WAT suggests the involvement of osmoregulatory hormones in reproductive control of desert adapted rodents.