Application of carboxylic-phosphinic mixed anhydrides in the fragment peptide synthesis of protected analogues of substance P

Mixed carboxylic-phosphinic anhydrides derived from peptide acids and 1-oxo-1-chlorophospholane have been applied in the synthesis of the protected [Leu¹¹]-SP_1-11 by the fragment coupling strategy. The yields from fragment couplings were ca. 75%, the products were of high purity while the conditions of formation and coupling of the corresponding mixed phosphinic anhydrides, for optimum yields, have been evaluated.     

Inhibition of the Renin‐Angiotensin System for Prevention of Atrial Fibrillation

Atrial fibrillation (AF) is a source of considerable morbidity and mortality. There has been compelling evidence supporting the role of renin‐angiotensin system (RAS) in the genesis and perpetuation of AF through atrial remodeling, and experimental studies have validated the utilization of RAS inhibition for AF prevention. This article reviews clinical trials on the use of angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) for the prevention of AF. Results have been variable, depending on the clinical background of treated patients. ACEIs and ARBs appear beneficial for primary prevention of AF in patients with heart failure, whereas they are not equally effective in hypertensive patients with normal left ventricular function. Furthermore, the use of ACEIs or ARBs for secondary prevention of AF has been found beneficial only after electrical cardioversion. Additional data are needed to establish the potential clinical role of renin‐angiotensin inhibition for prevention of AF. (PACE 2010; 33:1270–1285)     

Peptide Binding Sites Recognized by Anti-Mucin (MUC2) Monoclonal Antibodies

Multiple genes coding for human mucins have been identified (MUC1-5) and here monoclonal antibodies (MoAb) to a gastrointestinal mucin-MUC2 are examined. The antibodies were made to a synthetic peptide representing a single repeat in the core protein of the variable number of tandem repeat region. Using the six-mer overlapping peptides synthesized on polyethylene pins, different binding sites were detected by five anti-MUC 2 MoAbs. These contained amino acids: STTT, PTT, GTQTP, TPTP and PTTT (one antibody), and TPTPT. The repeat region of MUC2 essentially is hydrophobic, but contain useful immunogenic sites. This information will be useful for studying the structure and function of MUC2.     

Decreased CD3+CD16+ natural killer-like T-cell percentage and zeta-chain expression accompany chronic inflammation in haemodialysis patients

Aim:   Clinical and experimental data indicate a deficient immune response in haemodialysis (HD) patients. Natural killer-like (NKL) T cells express on their surface both the T-cell antigen receptor (TCR) and a diverse set of NK-cell receptors (NKR) and share properties of both T cells and NK cells. ζ-Chain phosphorylation is an early event that follows TCR activation or some NKR activation. The ζ-chain of both T cell and NK cells is downregulated in many chronic inflammatory states, HD included. In the present study, NKL T-cell percentage and ζ-chain expression in HD patients were evaluated.
Methods:   Thirty-three stable HD patients and 30 healthy volunteers were enrolled into the study. NKL T-cell percentage and NKL T-cell ζ-chain mean fluorescence intensity (MFI) were evaluated with flow cytometry. The inflammatory markers C-reactive protein, interleukin-6 and tumour necrosis factor-α were measured in the serum by means of enzyme-linked immunosorbent assay.
Results:   All the evaluated markers of inflammation were increased in HD patients. In these patients, NKL T-cell percentage (1.71 ± 1.69% vs 3.94 ± 3.86%) and ζ-chain MFI (3.66 ± 2.79 vs 7.03 ± 7.91) were decreased.
Conclusions:   NKL T-cell percentage and ζ-chain expression is decreased in HD patients. Taking into consideration the continuously increasing age of the HD patients and that normally NKL T-cell numbers increase with age counteracting the impaired T-cell and NK-cell function accompanying advancing age, the above NKL T-cell disturbances could contribute to the impaired immune response in this population. Measures towards alleviating chronic inflammation could partially restore NKL T-cell impairment.     

Congestive Heart Failure and VVI Pacing Mode: Dynamic Behavior of the Dispersion of Ventricular Repolarization

Dynamic Behavior of the Dispersion of Ventricular Repolarization. The aim of this study was to evaluate the circadian variation in the spatial dispersion of ventricular repolarization in continuously paced patients with congestive heart failure (CHF). Fourteen patients (10 males, 4 females, aged 65 ± 5 years) with CHF due to dilated cardiomyopathy (DCM) and an echocardiographic ejection fraction of 28%± 3% were studied. All patients underwent AV functional RF ablation and permanent pacemaker implantation for drug refractory chronic atrial fibrillation (AF). Patients were evaluated at 1 month postimplant with a three-channel 24-hour Holter monitor, using the three plane Frank orthogonal leads (X, Y, and Z), in VVI pacing mode at 70 beats/min. For each hour, the mean value of spike-T interval dispersion of the first five beats was measured. The control group consisted of 20 patients without structural heart disease, but with AF and complete AV block, continuously paced in WI mode at 70 beats/min. The dispersion of the spike-T interval had a circadian behavior in the study population, with higher values at night and lower during the daytime. During the daytime, the mean value of spike-T interval dispersion was 39 ± 5 ms and during the nighttime it was 45 ± 7 ms (P = 0.003). Such a difference between day and night was not found in the control group (38 ± 6 ms and 40 ± 8 ms, respectively, P = NS), In the daytime period the mean value of spike-T interval dispersion of our study population was comparable to that of the control group (P = NS), while during the nighttime it was significantly higher (P = 0.0004). In conclusion, by evaluating the dispersion of ventricular repolarization in two dimensions, space and time, a circadian variation was found in paced patients with CHF due to DCM. The increased QT dispersion in these patients during the nighttime period was attributed to different effects of vagal activity in normal and abnormal myocardial areas.     

Anti-peptide monoclonal antibodies to intestinal mucin 3

Second generation anti-peptide monoclonal antibodies were produced using synthetic peptide SIB35 (C-HSTPSFTSSITTTETTSHSTPSFTSSITTTETTS) as an antigen which contains two of the MUC3 tandem repeats. Three monoclonal antibodies were produced (M3.1, M3.2 and M3.3) which reacted with the immunizing peptide, but also reacted strongly with colon tissues. Using the immunoperoxidase staining technique, two of the monoclonal antibodies, M3.1 and M3.2, reacted with both colon carcinoma and normal colon tissue whereas the antibody M3.3 reacted with normal colon tissues but very weakly, if not at all, with colon carcinoma. MUC3 was found to be distributed in colon and rectum, and was also present to a lesser extent in breast, lung and salivary gland tissues. Analysis of mucin molecules by Western blotting, revealed the antigen detected by the antibodies (M3.1 and M3.2) to be of a high relative molecular mass. M3.1 and M3.3 reacted with epitopes SITTTE and PSFTSS, respectively. M3.2 did not react with any of the 6-mer peptides, even though it reacted with the full length VNTR (2 repeat peptide—SIB35). Anti-MUC3 peptide antibodies appear to react with colon, rectum, breast, salivary gland and lung tissues, and represent a new method of producing antitumour antibodies.     

Multiple-frequency tympanometry in children with acute otitis media

Multiple-frequency tympanometry (MFT) is a sweep-frequency method of acoustic immittance measurement, recently introduced in clinical practice. It provides values for the resonant frequency of the middle ear system. The purpose of this study was to use MFT to collect information about the mechanoacoustical changes occurring to the middle ear system after acute otitis media and to compare it with the results of conventional, low probe-tone tympanometry. Children with acute otitis media were followed up with both methods for 1 month after an episode of acute infection. Also, children with normal hearing were studied to establish normative data. Resonant frequency of the middle ear was found to be lower than normal even 1 month past the initial episode, for all types of 226-Hz tympanograms. MFT seemed to record changes in the middle ear after acute otitis media that 226-Hz tympanometry was unable to detect, implying persistence of pathology. More extended research will illuminate the clinical value of this method in the follow-up of acute otitis media.