Asymmetrically Substituted Poly(diitaconates) Obtained by Reversible Addition‐Fragmentation Chain Transfer (RAFT) Polymerization: Synthesis,Copolymerization Parameters,and Antimicrobial Activity

Asymmetrically substituted poly(diitaconate) copolymers are synthesized from 1‐((N‐tert‐butoxycarbonyl)‐2‐aminoethyl)‐4‐propyl diitaconate (PrIA) and different comonomers (N,N‐dimethyl‐acrylamide, DMAA; acrylic acid; or ((N‐tert‐butoxycarbonyl)‐2‐aminoethyl)methacrylate) by reversible addition–fragmentation chain transfer polymerization (RAFT). The RAFT copolymerization parameters of PrIA and DMAA are r_DMAA = 0.49 and r_PrIA = 0.17, compared to r_DMAA = 0.52 and r_PrIA = 0.54 obtained by free radical copolymerization (FRP). Thus, the RAFT process has a stronger trend to alternating polymerization than the FRP process. The polydispersity index of the RAFT copolymers is around 1.2–1.8, compared to 2.8–2.9 for the corresponding FRP copolymers. After removal of the tert‐butoxycarbonyl protective groups, antimicrobially active synthetic mimics of antimicrobial peptides are obtained. The thus activated poly(PrIA‐co‐DMAA) copolymers (repeat unit ratio 1:1) have an increasing activity against Escherichia coli and Staphylococcus aureus with increasing molar mass. The RAFT copolymers are slightly more active and less toxic than comparable FRP polymers, leading to a higher selectivity for bacteria over mammalian cells. Higher molar fractions of PrIA in poly(PrIA‐co‐DMAA) copolymers (up to 80 mol%) do not increase their antimicrobial activity; reduction of the BuIA content in poly(BuIA‐DMAA) (down to 10 mol%) leads to a loss of activity against both E. coli and S. aureus.     

Association of hyperhomocysteinemia with genetic variants in key enzymes of homocysteine metabolism and methotrexate toxicity in rheumatoid arthritis patients

Objectives

The study investigated the association between plasma homocysteine, folate and vitamin B12 with 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TYMS 2R → 3R) and methionine synthase (MTR A2756G) polymorphisms and methotrexate (MTX) treatment and toxicity in Tunisian Rheumatoid arthritis (RA) patients.

Methods

A total of 185 patients with RA were included. Homocysteine (Hcy) was assessed by fluorescence polarization immunoassay, and folate and vitamin B12 were measured by chemiluminescence immunoassays. The genetic polymorphisms were analyzed by PCR or PCR-RFLP. Hyperhomocysteinemia (HHC) was considered for Hcy?>?15 µmol/L.

Results

MTHFR C677T polymorphism was associated with HHC in RA patients (multi-adjusted OR, 95% CI 2.18, [1.07–4.57]; p?=?0.031). No association was detected with the remaining polymorphisms. Plasma Hcy, folate, and vitamin B12 did not differ according to each polymorphism, or with MTX treatment or toxicity. However, HHC was more prevalent in patients with than those without MTX toxicity (32.7 vs. 16.7%; p?=?0.035).

Conclusions

The MTHFR 677TT genotype is an independent risk factor for HHC in Tunisians RA patients. HHC could be a useful marker of MTX toxicity in RA patients.

     

Bacterial spondylodiskitis: pyogenic or tuberculous?

We retrospectively studied the epidemiological, clinical, radiological and evolutive aspects of bacterial spondylodiskitis observed in 39 patients diagnosed from January 1989 to December 1998, in order to find criteria to distinguish between pyogenic spondylodiskitis (PS) and tuberculous spondylodiskitis (TS). During the study period, we collected 13 patients (33.3%) with PS and 26 patients (66.7%) with TS. The mean age was 44 years. The delay in diagnosis was much longer in TS (8.4 months) than in PS (2 months). Diagnosis was certain in 6 cases (46%) of PS and in 12 cases (46%) of TS. Clinically, paravertebral abscesses and neurologic complications were significantly more frequent in TS. The main causative agents in PS were staphylococci. Diagnosis of spondylodiskitis is based on the imaging techniques, especially magnetic resonance imaging which is more sensitive and specific than computed tomography. Except in patients with positive blood cultures or positive urine culture in PS, and isolation of Mycobacterium tuberculosis in another visceral foci in TS, bacteriologic diagnosis was based on discovertebral needle biopsy. The yield of this technique was poor in our study (12.5%), even if bacteriologic confirmation of spondylodiskitis was made in 15 patients (38.5%). In the other cases, diagnosis rested on a set of clinical, biological and radiological criteria.     

Paucisymptomatic Dermoid Cyst with Fatal Outcome

Dermoid cysts of the central nervous system can cause devastating complications because of the mass effect of meningitis due to sinus tract. We report the case of a 5‐month‐old girl who presented with a crusted lesion of the occipital region of the scalp. Clinical examination noted skin abnormalities suggestive of occult dysraphism. Magnetic resonance imaging (MRI) was recommended, however, 40 days after this evaluation, and before the MRI could be performed, the girl presented with neurologic complications. Unfortunately, the diagnosis of dermoid cyst was made after the onset of severe complications that led to her death. The findings in this case emphasize the importance of more prompt MRI evaluation, particularly in cases where cranial or spinal dysraphism is suspected to have any connection to the skin as a pit or tract. Should we perform an urgent MRI for any cutaneous sign of dysraphism to avoid a dramatic evolution?     

Adaptive fault tolerant control design for Takagi–Sugeno fuzzy systems with interval time‐varying delay

This paper deals with the problem of fault‐tolerant control (FTC) of continuous‐time Takagi–Sugeno fuzzy systems with interval time‐varying delay by using adaptive observer. Through constructing an appropriate type of Lyapunov function, a delay‐dependent criterion is established to reduce the conservatism of designing an active FTC (AFTC). In comparison with the existing techniques in the literature, the proposed approach simplifies the design of an AFTC and gives in only one step of the estimate of state vector, the estimate of actuator fault and the controller gains. Some simulation examples are included to demonstrate the effectiveness of the proposed approach. Copyright © 2013 John Wiley & Sons, Ltd.     

Terlipressin in catecholamine-resistant septic shock patients

To determine the effects on hemodynamics, laboratory parameters, and renal function of terlipressin used in septic-shock patients with hypotension not responsive to high-dose norepinephrine (>2.0 microg x kg(-1) x min(-1)) and dopamine (25 microg x kg(-1) x min(-1)), a prospective, open-label study was carried out in 17 patients. Patients received one or two boluses of 1 mg of terlipressin. In all patients terlipressin induced a significant increase in mean arterial pressure (MAP), systemic vascular resistance, pulmonary vascular resistance, and left and right ventricular stroke work. The increase in MAP was accompanied by a significant decrease in heart rate and cardiac index, but stroke volume remained unchanged. Oxygen delivery and consumption were significantly decreased. Blood lactate concentrations significantly decreased over the study period. Bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly increased. Thrombocytes were significantly decreased. No change in prothrombin time was observed. Renal function, assessed by urine flow and creatinine clearance, was significantly improved. Pulmonary function assessed by Pao2/Fio2 ratio was not affected. A significant reduction in norepinephrine and dopamine infusion rates was observed in all patients. Eight patients died during their ICU stay from late multiple organ failure. Within the limitations of the present study (open-label design, small group of patients), it can be concluded that in septic shock patients with hypotension nonresponsive to fluid resuscitation and high-dose vasopressors, terlipressin can be effective to restore MAP. Cardiac index should be closely monitored because it was significantly decreased by terlipressin. Renal function was significantly improved. Mesenteric circulation was not evaluated, but hepatic function was altered during the study period. Further studies are required to determine whether terlipressin is safe in terms of outcome in septic shock patients.