Neurosyphilis with dementia and bilateral hippocampal atrophy on brain magnetic resonance imaging

Abstract Background This article reports a rare case of active neurosyphilis in a man with mild to moderate dementia and marked hippocampal atrophy, mimicking early onset Alzheimer’s disease. Few cases have so far described bilateral hippocampal atrophy mimicking Alzheimer’s disease in neurosyphilis. Case presentation The patient presented here is a 33 year old Bulgarian male, whose clinical features include progressive cognitive decline and behavioral changes over the last 18 months. Neuropsychological examination revealed mild to moderate dementia (Mini Mental State Examination score was 16/30) with impaired memory and attention, and executive dysfunction. Pyramidal, and extrapyramidal signs, as well as dysarthria and impairment in coordination, were documented. Brain magnetic resonance imaging showed cortical atrophy with noticeable bilateral hippocampal atrophy. The diagnosis of active neurosyphilis was based on positive results of the Venereal Disease Research Laboratory test/Treponema pallidum hemagglutination reactions in blood and cerebrospinal fluid samples. In addition, cerebrospinal fluid analysis showed pleocytosis and elevated protein levels. High-dose intravenous penicillin therapy was administered. At 6 month follow up, improvements were noted clinically, on neuropsychological examinations, and in cerebrospinal fluid samples. Conclusion This case underlines the importance of early diagnosis of neurosyphilis. The results suggest that neurosyphilis should be considered when magnetic resonance imaging results indicate mesiotemporal abnormalities and hippocampal atrophy. Neurosyphilis is a treatable condition which requires early aggressive antibiotic therapy.</p

Recent achievements in copper catalysis for C-N bonds formation

International audienceA mini-review describes the development of the catalysis by Cu(I) complexes aimed at the formation of C-N bonds at the Lomonosov MSU during 2010s. The main approach employs the amination of aryl and heteroaryl halides with the amines and polyamines, in this direction a great versatility of starting compounds was achieved: adamantanecontaining amines, linear diamines, oxadiamines and polyamines, various aryl iodides and bromides, derivatives of pyridine and quinoline were used for this purpose. In more peculiar cases, the copper catalysis was used for steroids transformations, including vinylation of azoles, widespread "click" reactions for the conjugate syntheses, and successful heterogenezation of the copper catalysts were also undertaken

Direct catalytic arylation of heteroarenes with meso-bromophenyl-substituted porphyrins

The arylation of mono-, di- and tetra-meso-bromophenyl-substituted porphyrins with the heteroarenes containing “acidic” C–H bonds, such as benzoxazole, benzothiazole and N-methylimidazole was studied in the presence of three alternative catalytic systems: Pd(dba)2/DavePhos/Cs2CO3, Pd(PPh3)4/PivOH/K2CO3 and Pd(OAc)2/Cu(OAc)2/PPh3/K2CO3. The first catalytic system was found to be successful in the reaction with benzoxazole, the second one was less efficient for our purpose, while the third system proved to be most versatile and afforded corresponding mono-, di-, tri- and even tetraarylated derivatives of porphyrins

Dietary Sodium Restriction Reduces Arterial Stiffness, Vascular TGF-β-Dependent Fibrosis and Marinobufagenin in Young Normotensive Rats

High salt (HS) intake stimulates the production of marinobufagenin (MBG), an endogenous steroidal Na/K-ATPase ligand, which activates profibrotic signaling. HS is accompanied by a blood pressure (BP) increase in salt-sensitive hypertension, but not in normotensive animals. Here, we investigated whether HS stimulates MBG production and activates transforming growth factor-beta (TGF-&beta;) profibrotic signaling in young normotensive rats, and whether these changes can be reversed by reducing salt to a normal salt (NS) level. Three-month old male Sprague&ndash;Dawley rats received NS for 4 and 8 weeks (0.5% NaCl; NS4 and NS8), or HS for 4 and 8 weeks (4% NaCl; HS4 and HS8), or HS for 4 weeks followed by NS for 4 weeks (HS4/NS4), n = 8/group. Systolic BP (SBP), pulse wave velocity (PWV), MBG excretion, aortic collagen 1&alpha;2, collagen 4&alpha;1 and TGF-&beta;, Smad2, Smad3, Fli-1 mRNA, and total collagen abundance were measured at baseline (BL), and on weeks 4 and 8. Statistical analysis was performed using one-way ANOVA. SBP was not affected by HS (125 &plusmn; 5 and 126 &plusmn; 6 vs. 128 &plusmn; 7 mmHg, HS4 and HS8 vs. BL, p &gt; 0.05). HS increased MBG (164 &plusmn; 19 vs. 103 &plusmn; 19 pmol/24 h/kg, HS4 vs. BL, p &lt; 0.05) and PWV (3.7 &plusmn; 0.2 vs. 2.7 &plusmn; 0.2 m/s, HS4 vs. NS4, p &lt; 0.05). HS8 was associated with a further increase in MBG and PWV, with an increase in aortic Col1a2 80%), Col4a1 (50%), Tgfb1 (30%), Smad2 (30%) and Smad3 (45%) mRNAs, and aortic wall collagen (180%) vs. NS8 (all p &lt; 0.05). NS following HS downregulated HS-induced factors: in HS4/NS4, the MBG level was 91 &plusmn; 12 pmol/24 h/kg (twofold lower than HS8, p &lt; 0.01), PWV was 3.7 &plusmn; 0.3 vs. 4.7 &plusmn; 0.2 m/s (HS4/NS4 vs. HS8, p &lt; 0.05), aortic wall Tgfb1, Col1a2, Col4a1, Smad2, Smad3 mRNAs, and collagen abundance were reversed by salt reduction to the BL levels (p &lt; 0.05). HS was associated with an activation of TGF-&beta; signaling, aortic fibrosis and aortic stiffness accompanied by an MBG increase in the absence of SBP changes in young normotensive rats. The reduction of dietary salt following HS decreased MBG, PWV, aortic wall collagen and TGF-&beta;. Thus, HS-induced aortic stiffness in normotensive animals occurred in the context of elevated MBG, which may activate SMAD-dependent TGF-&beta; pro-fibrotic signaling. This data suggests that a decrease in salt consumption could help to restore aortic elasticity and diminish the risk of cardiovascular disease by reducing the production of the pro-fibrotic factor MBG

Canrenone Restores Vasorelaxation Impaired by Marinobufagenin in Human Preeclampsia

Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). Recently, we demonstrated that (i) MBG induces fibrosis in rat tissues via a mechanism involving Fli1, a negative regulator of collagen-1 synthesis, and (ii) MBG sensitive Na/K-ATPase inhibition is reversed by mineralocorticoid antagonists. We hypothesized that in human PE elevated MBG level is associated with the development of fibrosis of the umbilical arteries and that this fibrosis can be attenuated by canrenone. Fifteen patients with PE (mean BP = 118 ± 4 mmHg; 34 ± 2 years; 38 ± 0.3 weeks gest. age) and twelve gestational age-matched normal pregnant subjects (mean BP = 92 ± 2 mmHg; 34 ± 1 years; 39 ± 0.2 weeks gest. age) were enrolled in the study. PE was associated with a higher plasma MBG level, with a four-fold decrease in Fli1 level and a three-fold increase in collagen-1 level in the PE umbilical arteries vs. those from the normal subjects (p 50 = 141 nmol/L vs. EC50 = 0.9 nmol/L; p < 0.001). The effects of PE on Fli1 and collagen-1 were blocked by the in vitro treatment of umbilical arteries by 10 μmol/L canrenone. Similar results were obtained for umbilical arteries pretreated with MBG. These data demonstrate that elevated MBG level is implicated in the development of the fibrosis of umbilical arteries in PE, and that this could be blocked by mineralocorticoid antagonists

Antibody to Marinobufagenin Reverses Placenta-Induced Fibrosis of Umbilical Arteries in Preeclampsia

Background: Previous studies implicated cardiotonic steroids, including Na/K-ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE). Immunoneutralization of heightened MBG by Digibind, a digoxin antibody, reduces blood pressure (BP) in patients with PE, and anti-MBG monoclonal antibody lessens BP in a rat model of PE. Recently, we demonstrated that MBG induces fibrosis in cardiovascular tissues via a mechanism involving inhibition of Fli-1, a nuclear transcription factor and a negative regulator of collagen-1 synthesis. Objectives and Methods: We hypothesized that in PE, elevated placental MBG levels are associated with development of fibrosis in umbilical arteries. Eleven patients with PE (mean BP 124 &plusmn; 4 mmHg; age 29 &plusmn; 2 years; 39 weeks gest. age) and 10 gestational age-matched normal pregnant subjects (mean BP 92 &plusmn; 2 mmHg; controls) were enrolled in the clinical study. Results: PE was associated with a higher placental (0.04 &plusmn; 0.01 vs. 0.49 &plusmn; 0.11 pmol/g; p &lt; 0.01) and plasma MBG (0.5 &plusmn; 0.1 vs. 1.6 &plusmn; 0.5 nmol/L; p &lt; 0.01), lower Na/K-ATPase activity in erythrocytes (2.7 &plusmn; 0.2 vs. 1.5 &plusmn; 0.2 &micro;mol Pi/mL/hr; p &lt; 0.01), 9-fold decrease of Fli-1 level and 2.5-fold increase of collagen-1 in placentae (p &lt; 0.01) vs. control. Incubation of umbilical arteries from control patients with 1 nmol/L MBG was associated with four-fold decrease in Fli-1 level and two-fold increase in collagen-1 level vs. those incubated with placebo (p &lt; 0.01), i.e., physiological concentration of MBG mimicked effect of PE in vitro. Collagen-1 abundance in umbilical arteries from PE patients was 4-fold higher than in control arteries, and this PE-associated fibrosis was reversed by monoclonal anti-MBG antibody ex vivo. Conclusion: These results demonstrate that elevated placental MBG level is implicated in the development of fibrosis of the placenta and umbilical arteries in PE