Metabolically controlled reperfusion in acute myocardial infarction: should the polarizing solution be given subselectively?

BACKGROUND: In working rat hearts, metabolic support of injured tissue enhances recovery after acute myocardial infarction. Clinical experience with a systemic "polarizing solution" supports this claim. OBJECTIVES: In a dog model of ischemia/reperfusion, we tested the feasibility of subselectively supplying adapted metabolic substrates before instituting blood reperfusion. METHODS: Thirty-five dogs underwent ligation of the proximal left anterior descending artery and collaterals for 90 minutes. The animals were randomly assigned to receive direct blood reperfusion (Group I), intracoronary glucose, insulin, and potassium (Group II), or intracoronary glucose, insulin, and potassium plus propionyl-L-carnitine (PLC) (Group III). After 30 minutes of artificial reperfusion, prograde blood flow was resumed in groups II and III. A routine necropsy was performed 3 to 5 days later. Primary endpoints were severe arrhythmias, death, markers of infarct size, and specific histologic features. RESULTS: We excluded 4 dogs for technical reasons and 2 others for preexisting cardiomyopathy. In the remaining 29 animals, large apical infarctions were documented ventriculographically during arterial ligation. One dog died of irreversible ventricular fibrillation during the initial ischemic period, and 9/28 dogs (32.1%) died during early reperfusion. Ventricular fibrillation was more common with 10% (versus 5%) dextrose concentrations and was eliminated by PLC. Irreversibly injured (versus jeopardized) areas of myocardium were more common in Group III (85.9 19.3%) than in Groups I and II (16.9 10.8%). CONCLUSION: Subselective infusion of metabolically supportive solutions during acute myocardial infarction is technically feasible. To prevent osmotic endothelial damage, the perfusate must have a low (< 5%) dextrose content.     

Circadian Rhythms of Heart Rate Variability in Hypertrophic Cardiomyopathy

Background: It has been hypothesized that an interaction between sympathetic nervous activity and an abnormal myocardium plays a role in the development and progression of hypertrophic cardiomyopathy (HCM). Methods: In the present study we investigated cardiac autonomic function by 24-hour spectral analysis of heart rate variability (HRV) in 18 patients with HCM, without evidence of heart failure, and 18 controls of similar age. Results: We found a significant reduction of 24 hour variance in HCM patients relative to controls (15,000 ± 9480 ms² vs 24,720 ± 12,450 ms² respectively; p < 0.05). Moreover, a loss of the expected day-night changes in the low frequency (LF) spectral component (expressed in normalized units), and LF/HF ratio (HF; high frequency component) were observed in HCM patients. Decreased day-night changes in LF/HF ratio were previously reported in patients with mild hypertension, uncomplicated coronary disease, and after myocardial infarction, conditions in which it seems to exist a higher than normal sympathetic activity. No significant correlations were found between HRV indices and echocardiographic standard measures of systolic and diastolic function parameters. Conclusions: These data are consistent with the presence of an alteration in neural modulation of heart period in HCM patients, noninvasively detectable by continuous 24 hour HRV analysis.     

Effects of chronic administration of PPAR-gamma ligand rosiglitazone in Cushing's disease

OBJECTIVE: Rosiglitazone, a thiazolidinedione compound with peroxisome proliferator-activated receptor-gamma (PPAR-gamma)-binding affinity, is able to suppress adrenocorticotropic hormone (ACTH) secretion in treated mice and in AtT20 pituitary tumor cells. These observations suggested that thiazolidinediones may be effective as therapy for Cushing's disease (CD). PATIENTS AND METHODS: Rosiglitazone (8 mg/day) was administered to 14 patients with active CD (13 women, one man, 18-68 years). Plasma ACTH, serum cortisol (F) and urinary free cortisol (UFC) levels were measured before and then monthly during rosiglitazone administration. RESULTS: In six patients a reduction of ACTH and F levels and a normalization of UFC were observed 30-60 days after the beginning of rosiglitazone administration: there was a significant difference between basal and post-treatment values for UFC (1238+/-211 vs 154+/-40 nmol/24 h, P<0.03), but not for ACTH (15.9+/-3.7 vs 7.9+/-0.9 pmol/l) and F levels (531+/-73 vs 344+/-58 nmol/l). Two of six cases, followed up for 7 months, showed a mild clinical improvement. Eight patients were nonresponders after 30-60 days of rosiglitazone treatment: their ACTH, F and UFC levels did not differ before and during drug administration. Immunohistochemical analysis of pituitary tumors removed from two responder and two nonresponder patients showed a similar intense immunoreactivity for PPAR-gamma in about 50% of cells. CONCLUSIONS: The administration of rosiglitazone seems able to normalize cortisol secretion in some patients with CD, at least for short periods. Whether the activation of PPAR-gamma by rosiglitazone might be effective as chronic pharmacologic treatment of CD needs a more extensive investigation through a randomized and controlled study.     

Electrochemical and optoelectronic properties of terthiophene- and bithiophene-based polybenzofulvene derivatives

The electrochemical behavior of some polybenzofulvene derivatives bearing bithiophene (BT) or terthiophene (TT) side chains was investigated by cyclic voltammetry. Very interestingly, the presence of unsubstituted terminal thiophene moieties allowed poly-6-BT-BF3k and poly-6-TT-BF3k to be cross-linked by electrochemical procedures. Conductive films were obtained by electrodeposition from solutions of these polymers onto electrode surfaces through the formation of covalent cross-linking due to dimerization (i.e. electrochemical oxidation) of the BT or TT side chains. The films showed electrochromic features and switched from yellow-orange (neutral) to green (positively charged) by switching the potential, and were stable to tenths of cycles, without degradation in the wet state in the electrolyte solution. Finally, the thin film obtained by electrodeposition of poly-6-TT-BF3k on a indium tin oxide (ITO) glass substrate showed in the neutral state a significantly red-shifted photoluminescence (PL) emission (∼40 nm red-shifted with respect to that of the corresponding film obtained by casting procedures), which was consistent with the presence of more conjugated moieties produced by the oxidative dimerization of the TT side chains. The innovative architecture and the easy preparation could lead to a broad range of applications in optoelectronics and bioelectronics for these cross-linked hybrid materials based on π-stacked polybenzofulvene backbones bearing oligothiophene side chains.

The electrochemical behavior of some polybenzofulvene derivatives bearing bithiophene (BT) or terthiophene (TT) side chains was investigated by cyclic voltammetry and cross-linked materials were obtained by dimerization of the BT or TT side chains.     

Gluten Psychosis: Confirmation of a New Clinical Entity

Non-celiac gluten sensitivity (NCGS) is a syndrome diagnosed in patients with symptoms that respond to removal of gluten from the diet, after celiac disease and wheat allergy have been excluded. NCGS has been related to neuro-psychiatric disorders, such as autism, schizophrenia and depression. A singular report of NCGS presenting with hallucinations has been described in an adult patient. We report a pediatric case of a psychotic disorder clearly related to NCGS and investigate the causes by a review of literature. The pathogenesis of neuro-psychiatric manifestations of NCGS is unclear. It has been hypothesized that: (a) a “leaky gut” allows some gluten peptides to cross the intestinal membrane and the blood brain barrier, affecting the endogenous opiate system and neurotransmission; or (b) gluten peptides may set up an innate immune response in the brain similar to that described in the gut mucosa, causing exposure from neuronal cells of a transglutaminase primarily expressed in the brain. The present case-report confirms that psychosis may be a manifestation of NCGS, and may also involve children; the diagnosis is difficult with many cases remaining undiagnosed. Well-designed prospective studies are needed to establish the real role of gluten as a triggering factor in neuro-psychiatric disorders.     

Suture pull-through insertion of graft donor in Descemet stripping automated endothelial keratoplasty: Results of 4-year follow-up

Purpose:

To report our clinical experience and 4-year follow-up results of Descemet stripping automated endothelial keratoplasty (DSAEK) with the suture pull-through insertion technique.

Methods:

This is a retrospective study of 195 eyes in which a posterior lamellar keratoplasty was performed between 2007 and 2011. The insertion of a folded donor lenticule was performed with a double-armed 10-0 suture using a straight transchamber needle and half-circle needle. Endothelial cell density was measured annually up to 4 years after the surgery, and cell loss was calculated based on the median preoperative donor endothelial cell density. Postoperative complications, primary graft failure, pupillary block, and dislocation of the donor tissue were assessed.

Results:

All patients underwent uncomplicated DSAEK. Data were available for 195 eyes (100%) at 1 year, 186 eyes (95.3%) at 2 years, 176 eyes (90.2%) at 3 years, and 160 eyes (82%) at 4 years. Median preop-erative donor endothelial cell density was 2688 cells/mm² [interquartile range (IQR) 207.5 cells/mm²], which decreased by 27% at 1 year (1956 cells/mm², IQR 264.8 cells/mm²), 31% at 2 years (1855 cells/mm², IQR 320.5 cells/mm²), 35% at 3 years (1756.5 cells/mm², IQR 306.5 cells/mm²), and 36% at 4 years (1709.5 cells/mm², IQR 288,0 cells/mm²). Nine patients (4.6%) had a dislocation of donor tissue; all were successfully reattached with a second air injection. Only three eyes (1.5%) developed graft failure. Pupillary block was present in 15 eyes (7.7%).

Conclusion:

DSAEK with suture pull-through insertion of donor graft represents a simplified and safe technique that has endothelial cell loss comparable with other techniques and low rates of intraoperative and postoperative complications.     

Swine Influenza A(H3N2) Virus Infection in Immunocompromised Man,Italy, 2014

Because swine influenza virus infection is seldom diagnosed in humans, its frequency might be underestimated. We report a immunocompromised hematologic patient with swine influenza A(H3N2) virus in 2014 in Italy. Local pigs were the source of this human infection.