Left ventricular external subannular plication: an indirect off-pump mitral annuloplasty method in a canine model

OBJECTIVE: Mitral annular dilatation in cardiomyopathy is due to left ventricular chamber enlargement. We hypothesized that the size of the mitral annulus could be "indirectly" reduced if the plicating sutures were placed externally into subannular myocardium. METHODS: In healthy mongrel dogs, an off-pump technique to create external subannular plication was designed and implemented. The sutures were placed directly into the myocardium below the atrioventricular groove. In 14 dogs, the sutures were tightened with tourniquets, and after a 30-minute observation period the hearts were arrested. Subsequently the mitral annular size was measured with the tourniquets still tight and then released. In 6 dogs, circumflex coronary blood flow, coronary blood flow reserve, and left ventricular systolic function were also measured during experiments. RESULTS: Subannular plication had no significant effect on the animals' hemodynamic stability, and it did not generate any arrhythmias. Suture tightening effectively reduced postmortem mitral annular diameter and circumference by 17% (30.8 +/- 0.4 mm and 96.8 +/- 1.1 mm vs 25.6 +/- 0.4 mm and 80.4 +/- 1.1 mm, respectively, P <.001) and mitral annular area by 31% (747 +/- 17 mm(2) vs 517 +/- 14 mm(2), P <.001). Circumflex coronary blood flow (39.0 +/- 7.9 mL/min vs 37.2 +/- 7.2 mL/min, P not significant) and left ventricular systolic function (dP/dt(max) 1705 +/- 237 mm Hg/s vs 1928 +/- 330 mm Hg/s, P not significant) remained unchanged (n = 6). CONCLUSION: In healthy hearts, subannular ventricular plication resulted in a significant indirect mitral annular size reduction without compromising circumflex coronary blood flow or left ventricular systolic performance.     

Highly potent 1,4-benzothiazine derivatives as K(ATP)-channel openers

A series of 1,4-benzothiazines, suitably functionalized at the N-4 and C-6 positions, arising from the replacement of a benzopyran-based structure of cromakalim with a 1,4-benzothiazine nucleus, has been synthesized as potassium channel openers (KCOs). Most of the tested compounds show high vasorelaxant potency that is considerably higher than that of the reference levcromakalim (LCRK). In the presence of the well-established selective K(ATP) blocker, glibenclamide, the vasorelaxing effects were antagonized in a competitive fashion, indicating the involvement of the K(ATP) channel in their pharmacological effect. Some aspects of the structure-activity relationship associated with the N-4 and C-6 substituents are discussed. The highest level of activity was achieved with a cyclopentenone ring at the N-4 position coupled with an electron-withdrawing group such as nitro, trifluoromethyl, or cyano at the C-6 position. Compounds 4c, 5c, and 6c displayed a vasorelaxant potency at least 10 000 times greater than that of LCRK, thus becoming the most potent KCOs identified to date.     

Differences in Monocyte Subsets and Monocyte-Platelet Aggregates in Acute Myocardial Infarction—PreliminaryResults

Background

Monocyte-platelet interaction may favor the development of a proatherogenic monocyte phenotype. It is still uncertain which of the 3 monocyte subpopulations interact with platelets to form monocyte-platelet aggregates (MPAs) in acute myocardial infarctions. The aim of our study was to evaluate the monocyte subsets, the percentage of MPAs and the involvement of monocyte subsets in MPA formation among patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), and compared to patients with stable angina (SA).

Modulation of 3-methylcholanthrene-induced rat hepatic and renal cytochrome P450 and phase II enzymes by plant phenols: protocatechuic and tannic acids

Naturally occurring phenolics, protocatechuic and tannic acids have been reported to be inhibitors of chemical mutagenesis and carcinogenesis in experimental models. Here, we have studied the effect of pretreatment with these compounds on MC-induced cytochrome P450 and phase II enzymes in rats. The male Wistar rats were treated intraperitoneally with protocatechuic acid and tannic acid in the dose of 50mg/kg every 3 days for 2 weeks. MC was administered at the 12th day of phenolics treatment. The activities of EROD (CYP1A1), MROD (CYP1A2), PROD (CYP2B), PNPH (CYP2E1), GST, UDPGT, NQO1 were measured in the liver and kidney. Protocatechuic acid treatment minimally reduced the MC-induced EROD and MROD, but the observed differences were statistically significant. This compound was also a weak inhibitor of hepatic PNPH. Moreover, Western blot analysis with CYP1A1/1A2- and CYP2E1-specific antibodies showed the same effect in the levels of hepatic CYP1A1/1A2 and CYP2E1. Minimal decrease of renal constitutive (by 23%) and more significant reduction of induced form (by 66%) of PNPH was found as result of treatment with protocatechuic acid. Tannic acid alone had no effect on cytochrome P450 enzymes while in combination with MC this polyphenol minimally enhanced the MC induction of MROD and in greater extent PNPH in liver. The treatment with protocatechuic acid alone enhanced slightly the activities of all three phase II enzymes in liver. The pretreatment with this phenolic of the MC-induced rats however significantly increased the activities of hepatic GST and NQO1 in comparison with MC-treated group. In kidney MC-induced activity of NQO1 was reduced (about 43%) to the control level by tannic acid pretreatment. The results of our present study indicate that in rat the prolonged treatment with protocatechuic acid affects differently the activities of CYP and phase II enzyme when compared to tannic acid. Moreover, the effect of this polyphenols significantly depends on the method of treatment.     

Endometriosis in pediatric and adolescent gynecology

Endometriosis is the most common cause of chronic pelvic pain in adolescent girls (50-70%), unresponsive to treatment of oral contraceptives and non-steroidal anti-inflammatory drugs. The most common symptoms of the disease are: acquired or progressive dysmenorrhea, acyclic and cyclic pain, dyspareunia (in sexually active girls), urological symptoms and gastrointestinal complaints. When evaluating an adolescent with suspected endometriosis, a gynecological examination (rectal or vaginal examination) and imaging studies (ultrasonography, magnetic resonance) should be performed. Moreover, in diagnostic process laparoscopy should be carried out in all girls and teenagers with chronic pelvic pain unresponsive to medical treatment. Initial therapy of endometriosis in adolescent girls involves: surgical methods (laparoscopy/laparotomy), hormonal pharmacotherapy (combined contraceptives, progestin-only protocols), GnRH agonists (adolescents over 16 years of age), non-steroidal anti-inflammatory drugs, alternative pain therapies and psychotherapy. Early diagnosis and treatment during adolescence may decrease disease progression and prevent subsequent infertility.     

Prolidase enzyme is required for extracellular matrix integrity and impacts on postnatal cerebellar cortex development

The extracellular matrix is essential for brain development, lamination, and synaptogenesis. In particular, the basement membrane below the pial meninx (pBM) is required for correct cortical development. The last step in the catabolism of the most abundant protein in pBM, collagen Type IV, requires prolidase, an exopeptidase cleaving the imidodipeptides containing pro or hyp at the C-terminal end. Mutations impairing prolidase activity lead in humans to the rare disease prolidase deficiency characterized by severe skin ulcers and mental impairment. Thus, the dark-like (dal) mouse, in which the prolidase is knocked-out, was used to investigate whether the deficiency of prolidase affects the neuronal maturation during development of a brain cortex area. Focusing on the cerebellar cortex, thinner collagen fibers and disorganized pBM were found. Aberrant cortical granule cell proliferation and migration occurred, associated to defects in brain lamination, and in particular in maturation of Purkinje neurons and formation of synaptic contacts. This study deeply elucidates a link between prolidase activity and neuronal maturation shedding new light on the molecular basis of functional aspects in the prolidase deficiency.     

Neurofibromatosis type 1 in children--with special consideration of ophthalmologic symptoms

PURPOSE: Analysis of neurofibromatosis type I in children with special respect to ophthalmological symptoms. METHODS: It was performed a retrospective review of 18 children in period 1986-2002. The authors analysed the clinical, especially ophthalmological data, and the treatment of ophthalmological signs. RESULTS: The most frequent were the skin symptoms. All of the 18 patients had cafe au lait spots; 4 children had cutane neurofibroma; In 3 patients plexiform neurofibroma were observed. Ocular symptoms were: cutane neurofibroma in the left upper eye lid: 1 case; Lisch nodules in the iris: 5 cases; bilateral optic pathway glioma: 3 cases. One child's bilateral gliomas were inoperable, because of the intracranial progression. One child underwent surgical treatment because of the extreme exophthalmus in the right eye. Her left eye's glioma and the third case bilateral glioma needed only observation because of the loss of clinical signs, and slow progression. Family examinations were also performed: 12 children had signs in the II., III. and IV. generations, there were no symptoms in 6 family, they were new mutations. CONCLUSIONS: The most serious cases had ophthalmological symptoms, namely bilateral visual pathway gliomas that could lead to blindness. The treatment needed individually medical decision.     

Association between IVS3 + 17T/C CD28 gene polymorphism and the acute kidney allograft rejection

CD28 is a costimulatory molecule which plays an important role in T cell-mediated immune response and transplantation. The aim of the present study was to examine the association between the IVS3 + 17T/C (rs3116496:T/C) polymorphism in the CD28 gene and the development of delayed renal graft function (DGF), as well as the acute rejection and chronic allograft nephropathy. A total of 270 recipients of the first renal transplants were included in the study. SNP within the CD28 gene was genotyped using TaqMan genotyping assay.Acute rejection was diagnosed in 21.74% of the carriers of the TT genotype, 33.33% of CT carriers and 60.00% of CC homozygotes. The odds of acute rejection were statistically significantly higher in carriers of the C allele (with CT or CC genotype) compared with TT homozygotes (CC + CT vs TT: OR = 1.93, 95%CI = 1.10–3.39, p = 0.026). There were no statistically significant associations between CD28 gene polymorphism and DGF as well as chronic allograft nephropathy.The results of our study suggest an association between IVS3 + 17T/C polymorphism in the CD28 gene and acute kidney allograft rejection.     

Relationship of quality of life to dispositional optimism,health locus of control and self-efficacy in older subjects living in different environments

Purpose  

To describe the relationship of dispositional optimism, health locus of control and self-efficacy to quality of life (QOL) in older subjects differing in level of disability and institutionalisation.     

Statin expression in the untreated and SarCNU-exposed human glioma cell line,SK-MG-1

Summary Cytokinetic analyses of gliomas and other neoplasms rely exclusively on the use of proliferation-dependent markers such as [³H]-thymidine and BuDR incorporation and the detection of growth-dependent proteins such as proliferating cell nuclear antigen (PCNA) and Ki-67. In normal tissues, the monoclonal antibody S-44 recognizes statin, a nuclear protein expressed only in nonproliferating cells. In the present study, indirect immunofluorescence microscopy using S-44 identified nuclear statin in 5.9% of a population of untreated human SK-MG-1 glioma cells in vitro. Incremental doses of the alkylating agent sarcosinamide chloroethylnitrosourea (SarCNU) induced a linear increase in the fraction of statin-positive SK-MG-1 cells. Labeling of nuclear statin with the monoclonal antibody S-44 may be a potentially useful marker of the cytotoxic effects of anticancer drugs in gliomas and other neoplastic tissues.