Serum vitamin D in patients with mild cognitive impairment and Alzheimer's disease

Objectives: To determine the relevance of Mini-Mental State Examination (MMSE), serum 25-hydroxyvitamin D (25(OH)D3), and 1,25(OH)2D3 concentrations to mild cognitive impairment (MCI) and various stages of Alzheimer's disease (AD). Materials and Methods: The study included 230 participants (>74 years) allocated to three main groups: 1-healthy subjects (HS, n = 61), 2-patients with MCI (n = 61), and 3- patients with Alzheimer's disease (AD) subdivided into three stages: mild (n = 41), moderate (n = 35), and severe AD (n = 32). The cognitive status was evaluated using MMSE. Serum 25 (OH)D3 (ng/ml) and 1,25(OH)2D3 concentrations (pg/ml) were determined by competitive radioimmunoassay. Results: MMSE scores and 25(OH)D3 were decreased in MCI and all stages of the AD in both genders. MMSE variability was due to gender in HS (11%) and to 25(OH)D3 in MCI (15%) and AD (26%). ROC analysis revealed an outstanding property of MMSE in diagnosis of MCI (AUC, 0.906; CI 95%, 0.847–0.965; sensitivity 82%; specificity, 98%) and AD (AUC, 0.997; CI 95%, 0.992–1; sensitivity, 100%; specificity, 98%). 25(OH)D3 exhibited good property in MCI (AUC, 0.765; CI 95%, 0.681–0.849; sensitivity, 90%; specificity, 54%) and an excellent property in diagnosis of AD (AUC, 0.843; CI 95%, 0.782–0.904; sensitivity, 97%; specificity, 79%). Logistic analyses revealed that, in MCI, MMSE could predict (or classify correctly) with 97.6% accuracy (Wald, 15.22, β, −0.162; SE, 0.554; OR = 0.115:0.039–0.341; p =.0001), whereas 25(OH)D3 with 80% accuracy (Wald, 41,013; β, −0.213; SE, 0.033; OR = 0.808: 0.757–863; p =.0001). 25(OH)D3 was the only significant predictor for the severe AD and contributed to MMSE variability. Age and gender were significant predictors only in the moderate AD. In patients with MCI, 25(OH)D3 and 1,25(OH)2D3 were correlated men, but in case of the AD, they were correlated in women. Conclusions: MMSE and serum 25(OH)D3 concentrations could be useful biomarkers for prediction and diagnosis of MCI and various stages of the AD. The results support the utility of vitamin D supplementation in AD therapy regimen. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc

Effect of nilvadipine on memory impairment and hippocampal malondialdehyde in rats with 4-vessel occlusion ischemia

Purpose: Nilvadipine is a dihydropyridine-type calcium channel blocker with emanating neuroprotective properties in various models of neuronal diseases. This study aimed at investigating the prophylactic effect of nilvadipine on memory impairment and hippocampal malodialdehyde (MDA) levels in global brain ischemia model induced by 4-vessel occlusion ischemia (4-VO) in rat. Materials and methods: The 4-VO ischemia was induced in Wistar rats by occluding the vertebral arteries permanently by cauterization. The common carotid arteries were twice occluded bilaterally for 10 minute at 60 minute interval. One week after 4-VO the memory was evaluated measuring the correct and error choices in 8-armed radial maze. The ischemiareperfusion- induced damage was evaluated measuring level of MDA in the hippocampus using thiobarbituric acid method. The study involved three groups: sham, ischemia-control and ischemia nilvadipin. Nilvadipine (3.2 mg/kg/day) was administerd for 7 days prior to 4-VO Results: The 4-VO impaired memory performance by decreasing the correct choices (long termreference memory) and increasing the error choices (short term-working memory) (p<0,001). Nilvadipine improved the performance by increasing the correct choices (p<0.002) and decreasing the error choices (p<0.05). Nilvadipine decreased (p<0.001) the elevated MDA induced by 4-VO. Conclusion: The prophylactic treatment with nilvadipine improved memory impairment and reduced the elevated hippocampal MDA induced by 4-VO. The prophylactic use of nilvadipine could be beneficial for inhibiting the ischemia related memory impairment in risky patients

Modulation of the negative inotropic effect of haloperidol by drugs with positive inotropic effects in isolated rabbit heart.

Haloperidol is a typical antipsychotic drug with inhibitory effects on dopamine and calcium homeostasis. In this study, the effect of haloperidol on the inotropism of rabbits' isolated heart was investigated by measuring the isovolumetric left ventricular pressure using a balloon in a modified Langendorff perfusion apparatus. Haloperidol at 0.01-0.3 micromol/l induced a negative inotropic effect (E(max) = 77.95 +/- 0.19; EC(50) = 0.043 +/- 0.002 micromol/l). The effect of haloperidol was decreased by Ca(2+) (E(max) = 42.93 +/- 3.22; EC(50) = 0.37 +/- 0.07 micromol/l; pD'(2) = 7.01 +/- 0.16), Bay K 8644 (E(max) = 30.75 +/- 1.33; EC(50) = 10.43 +/- 1.5 micromol/l, pD'(2) = 7.13 +/- 0.12), and digoxin (E(max ) = 42.03 +/- 3.72, EC(50) = 0.32 +/- 0.05 micromol/l, pD'(2) = 6.81 +/- 0.14). The effect of haloperidol was also reduced by norepinephrine (E(max) = 37.16 +/- 1.84; EC(50) = 1.73 +/- 0.24 micromol/l, pD'(2) = 6.97 +/- 0.08) and dopamine (E(max) = 35.68 +/- 2.78; EC(50) = 0.69 +/- 0.01 micromol/l, pD'(2 )7.48 +/- 0.15). However, the effect of haloperidol was nonsignificantly reduced by dobutamine (E(max) = 58.89 +/- 5.18; EC(50) = 0.15 +/- 0.06 micromol/l, pD'(2) = 5.88 +/- 0.47). These results show that the drugs that increase the influx of Ca(2+) into the cardiomyocyte decrease the negative inotropic effect of haloperidol, suggesting that the effect of haloperidol could be mediated via mechanisms involving actions on Ca(2+) entry into the cardiomyocyte. Haloperidol should be used carefully when prescribed for patients with cardiovascular disorders

in isolated rabbit heart preparation

We have investigated the inotropic effect of digoxin on isolated rabbit heart and changes caused by various drugs, Ca2+ and Mg2+ The isovolumetric left ventricular pressure was measured using a balloon in a modified Langendorff perfusion apparatus. Digoxin at 2.5 X 10(-7) - 0.5 X 10(-6) mM produced positive inotropic effect, whereas at 2 and 2.5 X 10(-6) mM there was a positive lusitropic action before the positive inotropic effect. Changes in the level of Ca2+ and Mg2+ significantly altered digoxin inotropicity. 5.04 mM of Ca2+ increased the positive inotropic effect of digoxin. Lowering the Ca2+ level to 1.26 mM or adding Mg2+ at 2.5 mM in the perfusion solution inhibited the inotropic effect. Atropine at 0.5 - 3 X 10(-5) M produced a weak positive inotropic effect. Verapamil (1 X 10(-6) - 3 X 10(-5) M), lidocaine (5 X 10(-6) - 3 X 10(-4) M) and propranolol (5 X 10(-6) - 3 X 10(-4) M) produced a negative inotropic effect. Diazepam at 5 X 10(-6) - 3 x 10(-4) M had a positive inotropic effect preceded by a brief negative inotropic effect. In the interaction studies, atropine non-significantly decreased the positive lusitropic effect of digoxin, but did not erect any significant action on the positive inotropic effect of digoxin. Verapamil, lidocaine and propranolol increased the positive lusitropic effect and antagonized the positive inotropic action of digoxin. Diazepam non-significantly modified the activity of digoxin. These results show the dose-dependent inotropic effect of digoxin, which was increased by Ca2+ and inhibited by Mg2+, verapamil, lidocaine and propranolol. The clinical significance of such interactions (decreased therapeutic and increased toxic effects) should be considered. Med Sci Res 27:759-764 (C) 1999 Lippincott Williams & Wilkins

in isolated rabbit heart preparation

We have investigated the inotropic effect of digoxin on isolated rabbit heart and changes caused by various drugs, Ca2+ and Mg2+ The isovolumetric left ventricular pressure was measured using a balloon in a modified Langendorff perfusion apparatus. Digoxin at 2.5 X 10(-7) - 0.5 X 10(-6) mM produced positive inotropic effect, whereas at 2 and 2.5 X 10(-6) mM there was a positive lusitropic action before the positive inotropic effect. Changes in the level of Ca2+ and Mg2+ significantly altered digoxin inotropicity. 5.04 mM of Ca2+ increased the positive inotropic effect of digoxin. Lowering the Ca2+ level to 1.26 mM or adding Mg2+ at 2.5 mM in the perfusion solution inhibited the inotropic effect. Atropine at 0.5 - 3 X 10(-5) M produced a weak positive inotropic effect. Verapamil (1 X 10(-6) - 3 X 10(-5) M), lidocaine (5 X 10(-6) - 3 X 10(-4) M) and propranolol (5 X 10(-6) - 3 X 10(-4) M) produced a negative inotropic effect. Diazepam at 5 X 10(-6) - 3 x 10(-4) M had a positive inotropic effect preceded by a brief negative inotropic effect. In the interaction studies, atropine non-significantly decreased the positive lusitropic effect of digoxin, but did not erect any significant action on the positive inotropic effect of digoxin. Verapamil, lidocaine and propranolol increased the positive lusitropic effect and antagonized the positive inotropic action of digoxin. Diazepam non-significantly modified the activity of digoxin. These results show the dose-dependent inotropic effect of digoxin, which was increased by Ca2+ and inhibited by Mg2+, verapamil, lidocaine and propranolol. The clinical significance of such interactions (decreased therapeutic and increased toxic effects) should be considered. Med Sci Res 27:759-764 (C) 1999 Lippincott Williams & Wilkins

Arthritis

Altered vascular reactivity due to endothelial dysfunction, consequent to vascular damage, is observed in rheumatoid arthritis. We investigated the effect of angiotensin (Ang)-(17) on vasculature changes in arthritis induced by complete Freund's adjuvant in male Wistar rats. Arthritis decreased soluble receptor for advanced glycation end products (sRAGE) whereas elevated aortic RAGE expression, increased interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), systolic blood pressure and the contractility induced by phenylephrine and KCl. Moreover, arthritis decreased the relaxing effect of acetylcholine. Neither arthritis nor Ang-(17) altered sodium nitroprusside relaxation. Ang-(1-7) reversed the effect of arthritis on TNF-alpha, sRAGE and RAGE expression without any effect on the IL-1 beta. Ang-(1-7) decreased phenylephrine and KCl contractility, especially in the endothelial-denuded aorta, whereas increased acetylcholine relaxation in the endothelial-intact aorta. Ang-(1-7) could find its place in the treatment protocol of arthritis and vascular diseases. (C) 2016 S. Karger AG, Base

Effect of Angiotensin-(1-7) on Aortic Response, TNF-α, IL-1β and Receptor for Advanced Glycation Endproduct in Rat's Adjuvant-Induced Arthritis.

Altered vascular reactivity due to endothelial dysfunction, consequent to vascular damage, is observed in rheumatoid arthritis. We investigated the effect of angiotensin (Ang)-(1-7) on vasculature changes in arthritis induced by complete Freund's adjuvant in male Wistar rats. Arthritis decreased soluble receptor for advanced glycation end products (sRAGE) whereas elevated aortic RAGE expression, increased interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), systolic blood pressure and the contractility induced by phenylephrine and KCl. Moreover, arthritis decreased the relaxing effect of acetylcholine. Neither arthritis nor Ang-(1-7) altered sodium nitroprusside relaxation. Ang-(1-7) reversed the effect of arthritis on TNF-α, sRAGE and RAGE expression without any effect on the IL-1β. Ang-(1-7) decreased phenylephrine and KCl contractility, especially in the endothelial-denuded aorta, whereas increased acetylcholine relaxation in the endothelial-intact aorta. Ang-(1-7) could find its place in the treatment protocol of arthritis and vascular diseases

Weekly cases of notifiable diseases, United States, U.S. territories, and Non-U.S. Residents weeks ending January 5, 2019 (week 01) Table1i Cryptosporidiosis; Cyclosporiasis

2019-01-Table1i -H.pdfCryptosporidiosis; Cyclosporiasis201

Serum Following Intraamygdaloid Injection

Amyloid beta-protein (A) assembly into toxic fibrillar structures is seminal in development of senile plaques, the pathological hallmark of Alzheimer's disease. Blocking this process could have a therapeutic value. beta-sheet breaker peptides (beta SBP) decrease A beta fibrillogenesis and neurotoxicity by preventing or dissolving misfolded A beta aggregates. The present study investigated the effects of beta SBPs on A beta 40-related neuropathology, memory impairment in 8-armed radial maze and expression of A beta 40 in brain and serum. A beta 40 was injected into amygdaloid nucleus followed 8 days later by octapeptide beta SBPs 15-22, 16-23 and 17-24. A beta 40 was detected not only in amygdala, but also in serum. A beta 40 induced cellular changes in amygdala and additionally in hippocampus. A beta 40 decreased correct choices, whereas increased errors (both number of arms revisited and total number of revisits) and latency of completing the maze test. The beta SBPs decreased A beta 40-induced pathological changes, memory impairment and A beta 40 expression in serum. The beta SBP15-22 distinctively decreased the total errors on day 14. The present results show that octapeptide beta SBPs corrected A beta 40-induced memory impairment, and support investigation of beta SBPs as a promising treatment of diseases characterized by neurodegeneration and memory impairment such as Alzheimer's disease