A novel versatile concept of cardioplegia delivery in cardiac surgery: The ReverseTWO cardioplegia circuit system.

Nowadays, the necessity of having a cardioplegia circuit capable of being adapted in order to administer different types of cardioplegia is strategically fundamental, both for the perfusionist and for the cardiac surgeon. This allows to avoid cutting tubes, guarantees sterility and, most of all, limits the number of cardioplegia circuits for the different strategies of cardiac arrest. The novel "ReverseTWO cardioplegia circuit system" is the development of the precedent "Reverse system" where mainly the 4:1 and crystalloid cardioplegia were used, It has the advantage of allowing immediate change of cardioplegia set-up versus four types of cardioplegia technique, when the strategy is unexpectedly changed before the beginning of cardiopulmonary bypass (CPB), is safe and enables the perfusionist to use one single custom pack of cardioplegia. Two pediatric roller pumps are usually used in our centre for cardioplegia administration; they have a standardized calibration (the leading with » inch and the follower with 1/8 inch) and the circuit consequently has two different tube diameters for the two different pumps. The presence in the circuit of two different shunts coupled with two different coloured clamps allows the immediate set-up for different cardioplegia administration techniques utilizing a colour-coding mechanism The aim of this manuscript is to present the new ReverseTWO Circuit. This novel system allows to administer four different cardioplegic solutions (4:1, 1:4, crystalloid, ematic) based on multiple tubes, which can be selectively clamped, identified through a color-coding method. The specificity of this circuit is the great versatility, which leads to numerous advantages, such as reduced risk of perfusion accident and reduced costs related not only to the purchase of different cardioplegia kits but also to the storage. https://youtu.be/ovJBE4ok2Ds.

Management of Microvascular Bleeding after On-Pump Cardiac Surgery in a Patient with Perioperative Diagnosis of Impairment of Platelet Responses to Adenosine Diphosphate: A Case Report and a Literature Review.

BACKGROUND: Impairment of platelet responses to adenosine diphosphate (ADP) is typified by mild to severe bleeding diathesis, easy bruising, excessive mucosal and post-operative bleeding. Patients lack full platelet activation and aggregation in response to ADP. Following research of the literature in Scopus, PubMed/MEDLINE, ScienceDirect, and the Cochrane Library, we report only 18 patients described to date with impaired platelet response to ADP, none of whom in the high bleeding-risk surgical setting or exploring potential therapeutic options. Data regarding population, putative genetic mutations, modes of inheritance, functional defects, and related clinical manifestations were retrieved from case series and case reports. CASE PRESENTATION: A 40-year-old woman was scheduled for on-pump cardiac surgery. Her past medical history included episodes of spontaneous mucocutaneous hemorrhages of the mild entity since childhood. Multiple electrode aggregometry (MEA, Multiplate® Roche Diagnostics, Rotkreuz, Switzerland) was used to evaluate platelet response to thrombin-activated peptide-6 (TRAP), arachidonic acid (ASPI), and ADP. An inadequate platelet aggregation induced using a high concentration of ADP with normal TRAP and ASPI tests was detected preoperatively. Therefore, intravenous desmopressin (DVVAP) 0.3 µg/kg body weight was administered to manage microvascular bleeding developed after weaning from cardiopulmonary bypass (CPB). CONCLUSIONS: Proper management of impaired platelet response to ADP requires a systematic assessment. The Multiplate analyzer is a valuable tool to promptly detect the disorder when a high clinical suspect is present and obtain insights during high bleeding-risk surgical procedures. DVVAP can be beneficial as first-line therapy in bleeding patients to improve platelet function.

Effect of Lockdowns on Hospital Staff in a COVID Center: A Retrospective Observational Study.

At the onset of the SARS-CoV-2 pandemic, individual and social measures were strengthened through restrictive non-pharmaceutical interventions, labelled with the term "lockdown". In Italy, there were two lockdowns (9 March 2020−3 May 2020 and 3 November 2020−27 March 2021). As part of preventive measures, healthcare workers and the administrative staff population of Policlinico A. Gemelli underwent nasopharyngeal swab tests from 1 March 2020 to 9 February 2022, a long time interval that includes the two aforementioned lockdowns. The population included 8958 people from 1 March 2020 to 31 December 2020; 8981 people from 1 January 2021 to 31 December 2021; and 8981 people from 1 January 2022 to 9 February 2022. We then analysed pseudo-anonymized data, using a retrospective observational approach to evaluate the impact of the lockdown on the incidence of SARS-CoV-2 infections within the population. Given the 14 day contagious period, the swab positivity rate (SPR) among the staff decreased significantly at the end of the first lockdown, every day prior to 18 May 2020, by 0.093 (p < 0.0001, CI = (−0.138−−0.047)). After the fourteenth day post the end of the first lockdown (18 May 2020), the SPR increased daily at a rate of 0.024 (p < 0.0001, 95% CI = (0.013−0.034)). In addition, the SPR appeared to increase significantly every day prior to 17 November 2020 by 0.024 (p < 0.0001, CI = (0.013−0.034)). After the fourteenth day post the start of the second lockdown (17 November 2020), the SPR decreased daily at a rate of 0.039 (p < 0.0001, 95% CI = (−0.050−−0.027)). These data demonstrate that, in our Institution, the lockdowns helped to both protect healthcare workers and maintain adequate standards of care for COVID and non-COVID patients for the duration of the state of emergency in Italy.

Evaluation of the Effectiveness and Safety of the BNT162b2 COVID-19 Vaccine in the Vaccination Campaign among the Health Workers of Fondazione Policlinico Universitario Agostino Gemelli IRCCS.

Health workers, especially those in patient-facing roles, had a significantly increased risk of COVID-19 infection, having serious outcomes, and risking spreading the virus to patients and staff. Vaccination campaign planning suggests allocating initial supplies of BNT162b2 vaccine to health workers given the importance of early protection to safeguard the continuity of care to patients. The aim of the study is to assess the effectiveness and safety of BNT162b2 vaccine among the health workers of Fondazione Policlinico Universitario Agostino Gemelli IRCCS (FPG). The retrospective cohort study was conducted among health staff working at the FPG. Vaccination data were collected from hospital records. The primary end points were vaccine effectiveness and safety. A total of 6649 health workers were included, of whom 5162 received injections. There were 14 cases of COVID-19 with onset at least 14 days after the second dose among vaccinated health workers and 45 cases among unvaccinated ones. BNT162b2 was 91.5% effective against COVID-19 (95% credible interval, 84.7% to 95.3%). The safety profile of BNT162b2 vaccine consisted of short-term, non-serious events. The promotion and boost of the COVID-19 vaccination campaign represents a key public health measure useful to curb the spread of the pandemic especially in vulnerable contexts, such as hospitals, where health workers carry out a paramount role for the entire community, and requires further protection with a possible booster dose in view of autumn-winter 2021.

Occupational hand dermatitis web survey in a university hospital during COVID-19 pandemic: the SHIELD study.

BACKGROUND: Occupational hand dermatitis (OHD) is a skin disease occurring on employees' hands in certain jobs. Little is known about prevalence, incidence and characteristics of this adverse skin reaction and its associated risk factors during COVID-19 pandemic. To evaluate both prevalence and incidence of OHD and associated risk factors in Italian clinicians. METHODS: A cross-sectional study was performed using a self-report questionnaire. RESULTS: Two hundred and thirty clinicians responded to the survey and 82% of responders did not report previous OHD history before the COVID-19 pandemic. Daily use of gloves was reported by 80% of responders. OHD prevalence was 18%, while incidence was 80%. We found a protective effect on symptom occurrence for vinyl/nitrile gloves if the time with gloves was ≥ 6 hours per day. CONCLUSIONS: This survey reveals a high OHD incidence in an Italian population of clinicians. Furthermore, wearing vinyl/nitrile gloves for at least 6 hours a day had a protective effect on symptom onset.

COVID-19 Seroprevalence among Healthcare Workers of a Large COVID-19 Hospital in Rome Reveals Strengths and Limits of Two Different Serological Tests.

Healthcare workers are at the forefront against COVID-19, worldwide. Since Fondazione Policlinico Universitario A. Gemelli (FPG) IRCCS was enlisted as a COVID-19 hospital, the healthcare workers deployed to COVID-19 wards were separated from those with limited/no exposure, whereas the administrative staff were designated to work from home. Between 4 June and 3 July 2020, an investigation was conducted to evaluate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (IgG) antibodies among the employees of the FPG using point-of-care (POC) and venous blood tests. Sensitivity, specificity, and predictive values were determined with reverse-transcription polymerase chain reaction on nasal/oropharyngeal swabs as the diagnostic gold standard. The participants enrolled amounted to 4777. Seroprevalence was 3.66% using the POC test and 1.19% using the venous blood test, with a significant difference (p < 0.05). The POC test sensitivity and specificity were, respectively, 63.64% (95% confidence interval (CI): 62.20% to 65.04%) and 96.64% (95% CI: 96.05% to 97.13%), while those of the venous blood test were, respectively, 78.79% (95% CI: 77.58% to 79.94%) and 99.36% (95% CI: 99.07% to 99.55%). Among the low-risk populations, the POC test's predictive values were 58.33% (positive) and 98.23% (negative), whereas those of the venous blood test were 92.86% (positive) and 98.53% (negative). According to our study, these serological tests cannot be a valid alternative to diagnose COVID-19 infection in progress.

Less is more: We are administering too much protamine in cardiac surgery.

Context: Protamine is routinely administered to neutralize the anticlotting effects of heparin, traditionally at a dose of 1 mg for every 100 IU of heparin-a 1:1 ratio protamine sparing effects-but this is based more on experience and practice than literature evidence. The use of Hemostasis Management System (HMS) allows an individualized heparin and protamine titration. This usually results in a decreased protamine dose, thus limiting its side effects, including paradox anticoagulation. Aims: This study aims to assess how the use of HMS allows to reduction of protamine administration while restoring the basal activated clotting time (ACT) at the end of cardiac surgery. Settings and Design: A retrospective observational study in a tertiary care university hospital. Subjects and Methods: We analyzed data from 42 consecutive patients undergoing cardiopulmonary bypass (CPB) for cardiac surgery. For all patients HMS tests were performed before and after CPB, to determine how much heparin was needed to reach target ACT, and how much protamine was needed to reverse it. Results: At the end of cardiopulmonary bypass, 2.2 ± 0.5 mg/kg of protamine was sufficient to reverse heparin effects. The protamine-to-heparin ratio was 0.56:1 over heparin total dose (a 44% reduction) and 0.84:1 over heparin initial dose (a 16% reduction). Conclusion: A lower dose of protamine was sufficient to revert heparin effects after cardiopulmonary bypass. While larger studies are needed to confirm these findings and detect differences in clinically relevant outcomes, the administration of a lower protamine dose is endorsed by current guidelines and may help to avoid the detrimental effects of protamine overdose, including paradox bleeding.

Mycobacterium chimaera in heater-cooler units: new technical approach for treatment, cleaning and disinfection protocol.

Mycobacterium chimaera infections have mainly been associated with the heater-cooler unit (HCU) and, ultimately, linked to contaminated aerosols in the operation room. The contamination status of HCUs seems to be influenced by the maintenance, therefore, according to the manufacturer's recommendations, peracetic acid (Puristeril) was introduced to increase HCU cleaning and disinfection protocol maintenance. Aerosol dispersion from Puristeril during maintenance can cause adverse effects to nearby workers. We aim to describe our technique to reduce the impact of Puristeril on operating room staff and to limit dispersion of its aerosol in the environment by performing the cleaning procedure through a closed circuit.

An innovative technique to improve safety of volatile anesthetics suction from the cardiopulmonary bypass circuit.

CONTEXT: Myocardial injury during cardiac surgery on cardiopulmonary bypass (CPB) is a major determinant of morbidity and mortality. Preclinical and clinical evidence of dose- and time-related cardioprotective effects of volatile anesthetic drugs exist and their use during the whole surgery duration could improve perioperative cardiac protection. Even if administering volatile agents during CPB are relatively easy, technical problems, such as waste gas scavenging, may prevent safe and manageable administration of halogenated vapors during CPB. AIMS: The aim of this study is to improve the safe administration of volatile anesthesia during CPB. SETTINGS AND DESIGN: Tertiary teaching hospital. SUBJECTS AND METHODS: We describe an original device that collects and disposes of any volatile anesthetic vapors present in the exit stream of the oxygenator, hence preventing its dispersal into the operating theatre environment and adaptively regulates pressure of oxygenator chamber in the CPB circuit. RESULTS: We have so far applied a prototype of this device in more than 1300 adult cardiac surgery patients who received volatile anesthetics during the CPB phase. CONCLUSIONS: Widespread implementation of scavenging system like the one we designed may facilitate the perfusionist and the anesthesiologist in delivering these cardioprotective drugs with beneficial impact on patients' outcome without compromising on safety.

Volatile anaesthetics added to cardiopulmonary bypass are associated with reduced cardiac troponin.

BACKGROUND: Every year, over 1 million cardiac surgical procedures are performed all over the world. Reducing myocardial necrosis could have strong implications in postoperative clinical outcomes. Volatile anaesthetics have cardiac protective properties in the perioperative period of cardiac surgery. However, little data exists on the administration of volatile agents during cardiopulmonary bypass. The aim of this study was to assess if volatile anaesthetics administration during cardiopulmonary bypass reduces cardiac troponin release after cardiac surgery. MATERIALS AND METHODS: We retrospectively analysed data from 942 patients who underwent cardiac surgery in a teaching hospital. The only difference between the groups was the management of anaesthesia during CPB. The volatile group received sevoflurane or desflurane while the control group received a combination of propofol infusion and fentanyl boluses. Patients who received volatile anaesthetics during cardiopulmonary bypass (n=314) were propensity-matched 1:2 with patients who did not receive volatile anaesthetics during CPB (n=628). RESULTS: We found a reduction in peak postoperative troponin I, from 7.8 ng/ml (4.8-13.1) in the non-volatile group to 6.8 ng/ml (3.7-11.8) in the volatile group (p=0.013), with no differences in mortality [2 (0.6%) in the volatile group and 2 (0.3%) in the non-volatile group (p=0.6)]. CONCLUSIONS: Adding volatile anaesthetics during cardiopulmonary bypass was associated with reduced peak postoperative troponin levels. Larger studies are required to confirm our data and to assess the effect of volatile agents on survival.

Particulate-phase mercury emissions from biomass burning and impact on resulting deposition: a modelling assessment.

Mercury (Hg) emissions from biomass burning (BB) are an important source of atmospheric Hg and a major factor driving the interannual variation of Hg concentrations in the troposphere. The greatest fraction of Hg from BB is released in the form of elemental Hg(Hg(g)0) . However, little is known about the fraction of Hg bound to particulate matter (HgP) released from BB, and the factors controlling this fraction are also uncertain. In light of the aims of the Minamata Convention to reduce intentional Hg use and emissions from anthropogenic activities, the relative importance of Hg emissions from BB will have an increasing impact on Hg deposition fluxes. Hg speciation is one of the most important factors determining the redistribution of Hg in the atmosphere and the geographical distribution of Hg deposition. Using the latest version of the Global Fire Emissions Database (GFEDv4.1s) and the global Hg chemistry transport model, ECHMERIT, the impact of Hg speciation in BB emissions, and the factors which influence speciation, on Hg deposition have been investigated for the year 2013. The role of other uncertainties related to physical and chemical atmospheric processes involving Hg and the influence of model parametrisations were also investigated, since their interactions with Hg speciation are complex. The comparison with atmospheric HgP concentrations observed at two remote sites, Amsterdam Island (AMD) and Manaus (MAN), in the Amazon showed a significant improvement when considering a fraction of HgP from BB. The set of sensitivity runs also showed how the quantity and geographical distribution of HgP emitted from BB has a limited impact on a global scale, although the inclusion of increasing fractions HgP does limit Hg(g)0 availability to the global atmospheric pool. This reduces the fraction of Hg from BB which deposits to the world's oceans from 71 to 62 %. The impact locally is, however, significant on northern boreal and tropical forests, where fires are frequent, uncontrolled and lead to notable Hg inputs to local ecosystems. In the light of ongoing climatic changes this effect could be potentially be exacerbated in the future.

Cardiac protection with phosphocreatine: a meta-analysis.

Phosphocreatine (PCr) plays an important role in the energy metabolism of the heart and a decrease in its intracellular concentration results in alteration of myocardium energetics and work. We conducted a meta-analysis of all randomized and matched trials that compared PCr with placebo or standard treatment in patients with coronary artery disease or chronic heart failure or in those undergoing cardiac surgery. We systematically searched PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials and Google Scholar up to 1 November 2015, for pertinent trials. The primary outcome was all-cause mortality. Secondary outcomes included inotrope use, ejection fraction (EF), peak creatinine kinase-myocardial band (CK-MB) release and the incidence of major arrhythmias, as well as spontaneous recovery of the heart performance in the subgroup of patients undergoing cardiac surgery with cardiopulmonary bypass. We pooled odds ratio (OR) and mean difference (MD) using fixed- and random effects models. We identified 41 controlled trials, of them 32 were randomized. Patients receiving PCr had lower all-cause mortality when compared with the control group [61/1731 (3.5%) vs 177/1667 (10.6%); OR: 0.71, 95% CI: 0.51-0.99; P = 0.04; I(2) = 0%; with 3400 patients and 22 trials included]. Phosphocreatine administration was associated with higher LVEF (MD: 3.82, 95% CI: 1.18-6.46; P = 0.005; I(2) = 98%), lower peak CK-MB release (MD: -6.08, 95% CI: -8.01, -4.15; P < 0.001; I(2) = 97%), lower rate of major arrhythmias (OR: 0.42; 95% CI: 0.27-0.66; P < 0.001; I(2) = 0%), lower incidence of inotropic support (OR: 0.39, 95% CI: 0.25-0.61; P < 0.001; I(2) = 56%) and a higher level of spontaneous recovery of the heart performance after cardiopulmonary bypass (OR: 3.49, 95% CI: 2.28-5.35; P < 0.001; I(2) = 49%) when compared with the control group. In a mixed population of patients with coronary artery disease, chronic heart failure or in those undergoing cardiac surgery, PCr may reduce all-cause short-term mortality. In addition, PCr administration was associated with improved cardiac outcomes. Owing to the pharmacological plausibility of this effect and to the concordance of the beneficial effects of PCr on several secondary but important outcomes and survival, there is urgent need for a large multicentre randomized trial to confirm these findings.

Tricks, tips, and literature review on the adapted vaporize system to deliver volatile agents during cardiopulmonary bypass.

BACKGROUND: Recently, evidence of cardio-protection and reduction in mortality due to the use of volatile agents during cardiac surgery led to an increase in their use during cardiopulmonary bypass (CPB). These findings seem to be enhanced when the volatile agents are used during all the surgical procedure, including the CPB period. AIMS: Since the administration of volatile agents through CPB can be beneficial to the patients, we decided to review the use of volatile agents vaporized in the CPB circuit and to summarize some tricks and tips of this technique using our 10-year experience of Brazilian and Italian centers with a large volume of cardiac surgeries. STUDY SETTING: Hospital. METHODS: A literature review. RESULTS: During the use of the volatile agents in CPB, it is very important to analyze all gases that come in and go out of the membrane oxygenators. The proper monitoring of inhaled and exhaled fraction of the gas allows not only monitoring of anesthesia level, but also the detection of possible leakage in the circuit. Any volatile agent in the membrane oxygenator is supposed to pollute the operating theater. This is the major reason why proper scavenging systems are always necessary when this technique is used. CONCLUSION: While waiting for industry upgrades, we recommend that volatile agents should be used during CPB only by skilled perfusionists and physicians with the aim to reduce postoperative morbidity and mortality.

Mercury in the Mediterranean. Part 2: processes and mass balance.

Mass balance of contaminants can provide useful information on the processes that influence their concentrations in various environmental compartments. The most important sources, sinks and the equilibrium or non-equilibrium state of the contaminant in individual environmental compartments can also be identified. Using the latest mercury speciation data, the results of numerical models and the results of recent studies on mercury transport and transformation processes in the marine environment, we have re-evaluated the total mercury (HgT) mass balance in the Mediterranean Sea. New calculations have been performed employing three distinct marine layers: the surface layer, the thermocline and the deep sea. New transport mechanisms, deep water formation and density-driven sinking and upwelling, were included in the mass balance calculations. The most recent data have even enabled the calculation of an approximate methylmercury (MeHg) mass balance. HgT is well balanced in the entire Mediterranean, and the discrepancies between inputs and outputs in individual layers do not exceed 20 %. The MeHg balance shows larger discrepancies between gains and losses due to measurement uncertainties and gaps in our knowledge of Hg species transformation processes. Nonetheless, the main sources and sinks of HgT (deposition and evasion) and MeHg (fluxes from sediment, outflow through the Gibraltar Strait) are in accordance with previous studies on mercury in the Mediterranean Basin. Mercury in the Mediterranean fish harvest is the second largest MeHg sink; about 300 kg of this toxic substance is consumed annually with sea food.

Development and application of a regional-scale atmospheric mercury model based on WRF/Chem: a Mediterranean area investigation.

The emission, transport, deposition and eventual fate of mercury (Hg) in the Mediterranean area has been studied using a modified version of the Weather Research and Forecasting model coupled with Chemistry (WRF/Chem). This model version has been developed specifically with the aim to simulate the atmospheric processes determining atmospheric Hg emissions, concentrations and deposition online at high spatial resolution. For this purpose, the gas phase chemistry of Hg and a parametrised representation of atmospheric Hg aqueous chemistry have been added to the regional acid deposition model version 2 chemical mechanism in WRF/Chem. Anthropogenic mercury emissions from the Arctic Monitoring and Assessment Programme included in the emissions preprocessor, mercury evasion from the sea surface and Hg released from biomass burning have also been included. Dry and wet deposition processes for Hg have been implemented. The model has been tested for the whole of 2009 using measurements of total gaseous mercury from the European Monitoring and Evaluation Programme monitoring network. Speciated measurement data of atmospheric elemental Hg, gaseous oxidised Hg and Hg associated with particulate matter, from a Mediterranean oceanographic campaign (June 2009), has permitted the model's ability to simulate the atmospheric redox chemistry of Hg to be assessed. The model results highlight the importance of both the boundary conditions employed and the accuracy of the mercury speciation in the emission database. The model has permitted the reevaluation of the deposition to, and the emission from, the Mediterranean Sea. In light of the well-known high concentrations of methylmercury in a number of Mediterranean fish species, this information is important in establishing the mass balance of Hg for the Mediterranean Sea. The model results support the idea that the Mediterranean Sea is a net source of Hg to the atmosphere and suggest that the net flux is ≈30 Mg year(-1) of elemental Hg.

Use of volatile anesthetics during cardiopulmonary bypass: a systematic review of adverse events.

OBJECTIVES: Recently, evidence of reduction in mortality due to the use of volatile agents during cardiac surgery led to an increase in their use during cardiopulmonary bypass (CPB). Because this technique could be beneficial to patients, but might present several hazards to new users, the authors decided to perform a systematic review of the main problems and complications. DESIGN: Systematic literature review. SETTING: Hospital. PARTICIPANTS: Adults undergoing cardiac surgery with use of volatile anesthetic agents during CPB. INTERVENTION: Several databases were searched for pertinent studies to identify all reports on the adverse events of using volatile agents during CPB and all randomized controlled trials using volatile agents during CPB. MEASUREMENTS AND MAIN RESULTS: Six nonrandomized trials reporting adverse events or complications with the use of volatile agents during CPB for cardiac surgery were identified: 2 reporting low transfer of isoflurane to the blood with diffusion membrane oxygenators; 2 reporting iatrogenic causes of damage after spilling liquid isoflurane onto the surface of the membrane oxygenators while filling the vaporizer; and 2 suggesting that the use of volatile agents during CPB increased the pollution of the room and the risk of occupational exposure of the operating room staff. On the other hand, no adverse event was reported in 19 studies that randomized 1,195 patients to receive isoflurane, desflurane, or sevoflurane during CPB. CONCLUSION: It is mandatory for industry to provide safe and easy-to-use devices to administer volatile agents during CPB with the standard membrane oxygenators.

Hesperidin gastroresistant microparticles by spray-drying: preparation, characterization, and dissolution profiles.

Gastroresistant microparticles for oral administration of hesperidin (Hd) were produced by spray-drying using cellulose acetate phthalate (CAP) as enteric polymer in different polymer/Hd weight ratio (1:1, 3:1, and 5:1), and a series of enhancers of the dissolution rate, such as sodium carboxymethylcellulose crosslinked (CMC), sodium dodecylbenzene sulfonate (SDBS), or Tween85. The raw materials and the microparticles were investigated by differential-scanning calorimetry, X-ray diffraction, infrared spectroscopy and imaged using scanning electron and fluorescence microscopy. In vitro dissolution tests were conducted using a pH-change method to investigate the influence of formulative parameters on the dissolution/release properties of the drug. CAP/Hd microparticles showed a good gastro-resistance but incomplete drug dissolution in the simulated intestinal fluid (SIF). The presence of the enhancers in the formulation produced well-formed microparticles with different size and morphology, containing the drug well coated by the polymer. All the enhancers were able to increase the dissolution rate of Hd in the simulated intestinal environment without altering CAP ability to protect Hd in the acidic fluid. The spray-drying technique and process conditions selected were effective in microencapsulating and stabilizing the flavonoid giving satisfactory encapsulation efficiency, product yield, and microparticles morphology, and a complete drug release in the intestine.

Antiproliferative oleanane saponins from Meryta denhamii.

Eight new oleanane saponins (1- 8) together with four know saponins (9-12) were isolated from the aerial parts of Meryta denhamii. Their structures were elucidated by 1D and 2D NMR experiments including 1D TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The antiproliferative activity of all compounds was evaluated using three murine and human cancer cell lines: J774.A1, HEK-293, and WEHI-164.

Electron spin-echo studies of spin-labelled lipid membranes and free fatty acids interacting with human serum albumin.

Human serum albumin (HSA) is an abundant plasma protein that transports fatty acids and also binds a wide variety of hydrophobic pharmacores. Echo-detected (ED) EPR spectra and D(2)O-electron spin echo envelope modulation (ESEEM) Fourier-transform spectra of spin-labelled free fatty acids and phospholipids were used jointly to investigate the binding of stearic acid to HSA and the adsorption of the protein on dipalmitoyl phosphatidylcholine (DPPC) membranes. In membranes, torsional librations are detected in the ED-spectra, the intensity of which depends on chain position at low temperature. Water penetration into the membrane is seen in the D(2)O-ESEEM spectra, the intensity of which decreases greatly at the middle of the membrane. Both the chain librational motion and the water penetration are only little affected by adsorption of serum albumin at the DPPC membrane surface. In contrast, both the librational motion and the accessibility of the chains to water are very different in the hydrophobic fatty acid binding sites of HSA from those in membranes. Indeed, the librational motion of bound fatty acids is suppressed at low temperature, and is similar for the different chain positions, at all temperatures. Correspondingly, all segments of the bound chains are accessible to water, to rather similar extents.