Innovative oral spray-dried Idebenone systems to improve patient compliance.

Idebenone is a high permeable drug with very slight water solubility that affects the dissolution rate in the biological fluids, causing an irregular and limited in vivo absorption after oral administration. Moreover, it is marketed in Europe as tablets equivalent to 150 mg, with the consequent administration of multiple dose of solid unit to obtain the correct dose, a deterrent for the patients' compliance. According to these considerations, our goal was to develop spray-dried microparticles using a soluble ß-cyclodextrin (CD) polymer and an enhancer of dissolution rate, such as carboxymethyl cellulose, to obtain a formulation easily dosable and soluble in water. The complex in solution was evaluated by phase solubility studies and the Idebenone/CD molar ratio selected was 1:1. According to Higuchi and Connors, adding carboxymethyl cellulose, a Bs-type profile was obtained. This result was due to the presence of carboxymethyl cellulose that competes with the CD in forming Idebenone microsystems, reducing of 10-fold the formulation bulk. UV-Vis absorption, (1)H nuclear magnetic resonance and circular dichroism showed the formation of the CD/Idebenone inclusion complex confirmed also by differential scanning calorimetry, Fourier transform infrared spectroscopy and fluorescence microscope (FM). The water solubility data and the in vitro dissolution tests performed in simulated gastric fluid, showed an increase of the drug water interaction due to the presence of the CD and carboxymethyl cellulose, both able to improve drug wettability, water solubility and dissolution rate. This approach seems to be suitable to produce microsystems which are able to enhance the in vivo absorption of Idebenone after oral administration and to increase the patient compliance.

Huge ascending aorta and aortic arch aneurysm in ultra octogenarian.

Giant ascending aorta aneurysms (AAA), which are larger than 10 cm, are rarely been reported (1-7). We hereby present the case of a giant AAA of about 11 cm in a very old women who was successfully operated on for ascending aorta and aortic arch replacement under deep hypothermic circulatory arrest.

Incorporation of a calixarene-based glucose functionalised bolaamphiphile into lipid bilayers for multivalent lectin recognition.

The synthesis, characterization and inclusion in liposomes of a glucosylated bolaamphiphile built on a calix[4]arene scaffold are described. The new glucocalixarene bolaamphiphile destabilizes bilayers of saturated lipids whereas it rigidifies those of unsaturated lipids, thus reducing leakage of calcein from the liposome internal aqueous compartment. Moreover, from fluorescence and turbidimetry experiments it was found that the glucose units of bolaamphiphile 1 functionalised liposomes allow a specific multivalent interaction with the tetrameric glucose binding protein Concanavalin A. These results therefore represent a novel strategy to functionalise liposomes with saccharides, exploiting multivalent glycosylated ligands to be used in the preparation of drug delivery systems potentially able to target specific lectins.

Two cases of right atrial myxoma in redo patients. A mere coincidence?

We describe two cases of right atrial myxoma in redo patients who had previously undergone to coronary artery by-pass grafting (CABGs) and mitral valve replacement respectively. Both of patients experienced effort dyspnea and were assessed by trans-thoracic echocardiography, revealing the right atrial masses. They were operated on for myxoma resection and postoperative course was uneventful. Our report deals with the interesting topic of the location of benign masses that are usually more common in the left atrium. Should we hypothesize that the right atrial manipulation during the previous surgery induces the onset of the right atrial mass? It is an interesting matter to debate.

Transcutaneous insertion of the Chitwood® clamp in case of minimally invasive cardiac surgery. Personal experience.

We describe a simple trick consisting of an insertion of a trans-thoracic Chitwood® clamp (Scanlan International, Inc, St Paul, MN, USA) through a small skin incision (<1cm), via the second intercostal space along the anterior axillary line, in case of minimally invasive mitral surgery, through right thoracotomy. This trick has been used in more than 100 patients and no complication or discomfort have been reported so far.

Additional applications of the Foley catheter in cardiac surgery.

We describe an additional use of the Foley catheter for preoperative and postoperative evaluation of the regurgitant mitral valve.

The Actis-gouge: a simple cutting tool for proper muscular resection in hypertrophic cardiomyopathy.

BACKGROUND: Surgical treatment of hypertrophic cardiomyopathy (HC) may be challenging for the risk of surgical complications or insufficient resection. We present our cutting tool to perform proper muscular resection in HC. MATERIAL AND METHODS: Ten patients (5 males, mean age 43,1 +/- 19,6 years, range 9-70 years) were operated on for HC using this semicircular cutting device. Combined procedures were : mitral valve repair (n = 1), mitral valve replacement (n = 2), right ventricular myectomy (n = 1), aortic valve replacement (n = 1), mitral and aortic replacement (n = 1). RESULTS: There was one early death. All the surviving patients are alive over a variable follow up from 2 to 8 years, with consistent reduction of symptoms: in fact, no patient had residual angina with significant reduction of the NYHA class from 3,2 +/- 0,6 to 1,3 +/- 0,5 postoperatively (p < 0,05). Muscular resection was effective with significant reduction of sub-valvular gradient from 84.5 + 33,4 mmHg to 14,1 +/- 17,6 mmHg (p < 0,05) without complications such as complete atrio-ventricular block or ventricular septal defects. CONCLUSION: Our semicircular myotome is an effective tool to perform a safe myectomy and it avoids surgical complications such as atrio-ventricular blocks or sub-valvular injuries. Our experience suggests that this cutting tool offers a reproducible method for muscular resection and it shows appreciable effects in the reduction of sub-valvular gradient with promising results in terms of morbidity and mortality.

Aortic valve replacement through the upper ministernotomy: preliminary experience with modified technique.

Minimally invasive approach for aortic valve surgery has been developed since 1995, reducing the complications related to the full sternotomy. We have introduced a new method for central cannulation that reduces the length of surgical incision for the aortic valve replacement through upper mini-sternotomy. To improve the surgical view without enlargement of the incision, two small additional incisions are performed for both arterial and atrial cannulation. We have used the modified technique in 60 patients without sternal infection or other surgical complications and with good cosmetic results.

Transmyocardial laser revascularization. Personal experience.

BACKGROUND: Indirect revascularization is a therapeutic approach in case of severe angina not suitable for percutaneous or surgical revascularization. Transmyocardial revascularization (TMR) is one of the techniques used for indirect revascularization and it allows to create transmyocardial channels by a laser energy bundle delivered on left ventricular epicardial surface. Benefits of the procedure are related mainly to the angiogenesis caused by inflammation and secondly to the destruction of the nervous fibers of the heart. PATIENTS AND METHOD: From September 1996 up to July 1997, 14 patients (9 males - 66.7%, mean age 64.8±7.9 years) underwent TMR. All patients referred angina at rest; Canadian Angina Class was IV in 7 patients (58.3%), III in 5 (41.7%). Before the enrollment, coronarography was routinely performed to find out the feasibility of Coronary Artery Bypass Graft (CABG): 13 patients (91,6%) had coronary arteries lesions not suitable for direct revascularization; this condition was limited only to postero-lateral area in one patient submitted to combined TMR + CABG procedures. RESULTS: Mean discharge time was 3,2±1,3 days after surgery. All patients were discharged in good clinical conditions. Perfusion thallium scintigraphy was performed in 7 patients at a mean follow-up of 4±2 months, showing in all but one an improvement of perfusion defects. Moreover an exercise treadmill improvement was observed in the same patients and all of them are in good clinical conditions, with significantly reduced use of active drugs. CONCLUSION; Our experience confirms that TMR is a safe and feasible procedure and it offers a therapeutic solution in case of untreatable angina. Moreover, it could be a hybrid approach for patients undergoing CABGs in case of absence of vessels suitable for surgical approach in limited areas of the heart.

Methane production from acetate and associated methane fluxes from anoxic coastal sediments.

The apparent microbial conversion of acetate to methane ranges seasonally from 0.7 to 88 micromoles per liter of whole wet sediment per hour in the top 5 centimeters of methane-producing sediments underlying sulfate-reducing sediments in Cape Lookout Bight, North Carolina. The associated methane flux across the sediment-water interface into overlying waters exhibits the same seasonal pattern. Significant methane production from acetate is observed only in sulfate-depleted sediments.

Single versus double lung transplantation in pulmonary fibrosis: a debated topic.

Idiopathic pulmonary fibrosis (IPF) represents the second most frequent indication for lung transplantation after chronic obstructive pulmonary disease. Survival rate after transplantation is poorer compared with other lung diseases for reasons that are not completely clear. Medical therapy with anti-inflammatory drugs may improve symptoms and quality of life, but it does not influence the survival rate. Lung transplantation is the best therapy for end-stage IPF. The debate regarding the superiority of double lung transplantation (DLT) compared with single lung transplantation (SLT) is still ongoing. Until some years ago, SLT was almost uniformly utilized for this indication. In the most recent years, a larger application of DLT has been observed worldwide, probably related to higher 1-year and 5-year survivals. The unanswered question is whether it is ethical to use two lungs for the same patient, considering the donor shortage, when a single lung would suffice. Many reports have demonstrated that SLT offers acceptable pulmonary function and satisfactory early and intermediate survival. Probably DLT should be reserved for younger recipients, for those with concomitant or possible chronic infection of the contralateral lung, or cases of marginal donors. Further studies will be needed to formulate recommendations regarding the preferred surgical approach in IPF.

A prospective study of prevalence of 60-days postoperative wound infections after cardiac surgery. An updated risk factor analysis.

AIM: Postoperative wound infections generally cause considerable extra morbidity, mortality and costs. The prevalence of total wound infections after cardiac surgery, including both sternal wound and donor site infections, ranges from 1.3 to 12.8%. The present study was conducted to identify the incidence of wound infections following cardiac surgery, to identify the risk factors and evaluate the efficacy of present modes of management. METHODS: From September 2004 to May 2005, 493 consecutive patients undergoing cardiac surgery were included in the study and were followed for the prevalence of surgical site infection (SSI) up to 60 days postoperatively. The wound infections were defined according to the Centers for Disease Control and Prevention (CDC) and U.S. National Nosocomial Infections Surveillance (NNIS) system criteria. RESULTS: The total incidence of SSI was 3.9%. Sternal wound infection (SWI) occurred in 17 patients (3.4%). Superficial wound infection was diagnosed in 10 patients (2%) and deep wound infection in 7 patients (1.4%). Donor site infection (DSI) occurred in 2 patients (0.4%). Early reoperation for bleeding, postoperative dialysis and the use of one internal mammary artery were independently associated with an increased risk of SWI. CONCLUSION: Preventing SSI in the operating room is the primary goal of the surgical team. Attention should be paid to antibiotic prophylaxis and Methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage treatment. The identification of risk factors will help to further reduce the incidence of wound infection.

Reinitiation of protein synthesis in Escherichia coli can be induced by mRNA cis-elements unrelated to canonical translation initiation signals.

In Eubacteria, de novo translation of some internal cistrons may be inefficient or impossible unless the 5' neighboring cistron is also translated (translational coupling). Translation reinitiation is an extreme case of translational coupling in which translation of a message depends entirely on the presence of a nearby terminating ribosome. In this work, the characteristics of mRNA cis-elements inducing the reinitiation process in Escherichia coli have been investigated using a combinatorial approach. A number of novel translational reinitiation sequences (TRSs) were thus identified, which show a wide range of reinitiation activities fully dependent on a translational coupling event and unrelated to the presence/absence of secondary structure or mRNA stability. Moreover, some of the isolated TRSs are similar to intercistronic sequences present in the E. coli genome.

Effect of glucagon infusion on plasma cyclic AMP in patients with cholestatic hepatitis and obstructive jaundice. New test of hepatic cholestasis.

Plasma cyclic AMP concentration during glucagon infusion at various time intervals was determined in 8 normal subjects, 9 patients with extrahepatic obstructive jaundice and 10 patients with cholestatic hepatitis (hepatitis A and B). Plasma cyclic AMP concentrations (pmol/ml) during glucagon infusion in patients with both obstructive jaundice and cholestatic hepatitis were found to be greater than those in control subjects. In addition, a significant difference in plasma cyclic AMP concentrations was found between patients with cholestatic hepatitis and obstructive jaundice at the 10th minute of glucagon infusion. These results indicate that plasma cyclic AMP levels at the 10th minute of glucagon infusion represent a reliable diagnostic index of cholestatic jaundice.

Cell specific enzyme markers as indicators of neurotoxicity: effects of acute exposure to methylmercury.

In order to assess the sensitivity of several cell specific enzyme markers (tyrosine hydroxylase (TH), glutamic acid decarboxylase, choline acetyltransferase, glutamine synthetase (GS), neuron specific and non-neuronal enolase and 2',3'-cyclic nucleotide phosphohydrolase (CNP] as indices of neurotoxicity, changes in their activities were monitored after rats were treated with two doses of the neurotoxic agent, methylmercury chloride (MMC). Comparisons were also made of any histopathological changes occurring in the tissues examined. At the low dose rate (3.36 mg Hg/kg, po, for 14 days), the rats exhibited less body weight gain compared to untreated animals. No change in either the neuronal or noneuronal enzyme markers was observed in brain but a significant increase in the myelin marker, CNP, and total enolase activity was seen in the optic nerve. Morphological evaluation by light microscopy indicated no discernible neuronal lesions in MMC-exposed animals. At the higher MMC dose (7.05 mg Hg/kg, po, for 7 days), there was about a 20% loss in the body weight of treated animals and partial hind limb paralysis was observed. Of all the neuronal marker enzymes examined, only TH was found to be decreased in the striatum. The proliferating astroglial marker, GS, was elevated only in the cerebellum. CNP was found to be decreased in both the optic and sciatic nerve. As in the lower dose group no pathological changes were observed at the light microscopic level in the brain of MMC-treated rats. These data suggest that of the cell specific marker enzymes studied, GS in the cerebellum and TH in the striatum may be useful biochemical markers for the neurotoxic action of MMC.

Effect of chronic exposure to hexachlorophene on rat brain cell specific marker enzymes.

The neurotoxicity associated with chronic exposure to hexachlorophene (HCP) was evaluated by measuring the activity of seven cell specific marker enzymes in brain and by comparing these measurements to morphological changes analyzed by light microscopy. Animals were divided into two groups, the experimental group received HCP at a daily dose of 20 mg/kg p.o. for 53 consecutive days whereas the control group received an equivalent amount of the vehicle only. HCP produced no change in the rate of gain in body weight nor did it produce a statistically significant change in brain weight. Furthermore, no overt abnormal neurological symptoms were observed at this level of exposure to HCP. The white matter throughout the brain was extensively vacuolated in the HCP-treated rats, imparting a spongiform structure which was absent in the white matter of the control animal brains. The data obtained reveal that chronic HCP treatment produce little change in any of the neuronal marker enzymes with the exception of a significant decrease in tyrosine hydroxylase activity in the striatum. Of the nonneuronal enzymes assayed, a significant increase in non-neuronal enolase, glutamine synthetase, and 2',3'-cyclic nucleotide phosphohydrolase was observed in the sciatic nerve, hippocampus and optic nerve, respectively.

An ultrastructural study of the craniocaudal continuation of the glycogen body.

An ultrastructural analysis of the chicken glycogen body and its craniocaudal continuation areas shows a continuum of astroglial cell types. Characteristic glycogen body astroglia are confined to the classically defined body located in the chicken lumbosacral spinal cord. These are large cells which have an eccentric dark nucleus surrounded by a rim of dense cytoplasm which contains the usual complement of organelles. The remainder of the cell volume is occupied by alpha and beta glycogen particles interspersed with a flocculo-granular material continuous with the main cytoplasmic mass. Astroglial cells of continuation areas usually have a light cytoplasm and a centrally placed nucleus. They contain beta glycogen particles of varying sizes, but like the glycogen body cells, may have beta particles as large as 48 nm. Such particles, which resemble four leaf clovers in shape, are suggestive of an ordered substructure. Gliofilaments are not always conspicuous in astroglial perikarya, but large numbers of them are present in the processes. Although the continuation areas are mostly confined to gray matter regions, the contained astroglial processes exhibit circular, triangular, or cylindrical shapes and form an unpatterned mosaic. Astrocytic processes forming the glia limitans on the anterior and posterior margins of the cord often contain conspicuous amounts of glycogen. The ultrastructural identification of such large amounts of glycogen within the chicken nervous system suggests that it plays a major role in avian neural metabolism.

The craniocaudal extent of the glycogen body in the domestic chicken.

All birds have a glial enclosed, glycogen-containing structure in the lumbosacral region of their spinal cords. Recently, a dorsal, central, glycogen-rich area surrounding the central canal in the brachial spinal cord was described in domestic chickens. In order to topographically delineate and histochemically describe this structure, fresh, frozen serial sections of chicken brains and spinal cords were processed for glycogen content, phosphorylase, succinic dehydrogenase and cholinesterase activities. The glycogen-rich area surrounding the central canal in the lumbosacral region is found at all levels of the spinal cord and lower medulla. In the upper medulla, it is located in the medline floor immediately ventral to the ependyma. It persists in this position until the level of the oculomotor complex where it ends. Phosphorylase positive regions closely parallel the glycogen distribution. No succinic dehydrogenase or cholinesterase activities are found in these areas.