Outcomes of normothermic machine perfusion of liver grafts in repeat liver transplantation (NAPLES initiative).

BACKGROUND: Retransplantation candidates are disadvantaged owing to lack of good-quality liver grafts. Strategies that can facilitate transplantation of suboptimal grafts into retransplant candidates require investigation. The aim was to determine whether late liver retransplantation can be performed safely with suboptimal grafts, following normothermic machine perfusion. METHODS: A prospectively enrolled group of patients who required liver retransplantation received a suboptimal graft preserved via normothermic machine perfusion. This group was compared with both historical and contemporaneous cohorts of patient who received grafts preserved by cold storage. The primary outcome was 6-month graft and patient survival. RESULTS: The normothermic machine perfusion group comprised 26 patients. The historical (cold storage 1) and contemporaneous (cold storage 2) groups comprised 31 and 25 patients respectively. The 6-month graft survival rate did not differ between groups (cold storage 1, 27 of 31, cold storage 2, 22 of 25; normothermic machine perfusion, 22 of 26; P = 0.934). This was despite the normothermic machine perfusion group having significantly more steatotic grafts (8 of 31, 7 of 25, and 14 of 26 respectively; P = 0.006) and grafts previously declined by at least one other transplant centre (5 of 31, 9 of 25, and 21 of 26; P < 0.001). CONCLUSION: In liver retransplantation, normothermic machine perfusion can safely expand graft options without compromising short-term outcomes.

Liver transplantation is a life-saving procedure for many different diseases. In the UK, one in 10 patients awaiting transplant have had a previous liver transplant. These retransplant operations are complex, and the general belief is that a good-quality donor liver graft is required for best outcomes. However, there is a significant shortage of good-quality organs for liver transplantation, so many patients awaiting retransplantation spend longer on the waiting list. This study investigated whether a new technology, called normothermic machine perfusion, could be used to preserve lower-quality donor livers and have successful outcomes for patients undergoing retransplantation. Traditionally, good-quality livers are preserved in an ice box and the study compared the outcomes of these two different approaches. The aim was to prove that normothermic machine perfusion improves access to transplantation for this group of patients, without compromising outcomes. A group of patients who underwent retransplantation and received a lesser-quality liver preserved with normothermic machine perfusion was compared with two groups of patients who had received a transplant with traditional ice-box preservation. The complications, graft, and patient survival of the former group was compared with those in the latter two groups who underwent liver retransplantation with better-quality liver grafts. The rate of survival and adverse surgical outcomes were comparable between the groups of patients who received a liver preserved via traditional ice-box preservation, and those who received a lesser-quality liver preserved via normothermic machine perfusion. Normothermic machine perfusion can potentially expand the number of suitable donor livers available for retransplant candidates.

Cardiac-specific deletion of voltage dependent anion channel 2 leads to dilated cardiomyopathy by altering calcium homeostasis.

Voltage dependent anion channel 2 (VDAC2) is an outer mitochondrial membrane porin known to play a significant role in apoptosis and calcium signaling. Abnormalities in calcium homeostasis often leads to electrical and contractile dysfunction and can cause dilated cardiomyopathy and heart failure. However, the specific role of VDAC2 in intracellular calcium dynamics and cardiac function is not well understood. To elucidate the role of VDAC2 in calcium homeostasis, we generated a cardiac ventricular myocyte-specific developmental deletion of Vdac2 in mice. Our results indicate that loss of VDAC2 in the myocardium causes severe impairment in excitation-contraction coupling by altering both intracellular and mitochondrial calcium signaling. We also observed adverse cardiac remodeling which progressed to severe cardiomyopathy and death. Reintroduction of VDAC2 in 6-week-old knock-out mice partially rescued the cardiomyopathy phenotype. Activation of VDAC2 by efsevin increased cardiac contractile force in a mouse model of pressure-overload induced heart failure. In conclusion, our findings demonstrate that VDAC2 plays a crucial role in cardiac function by influencing cellular calcium signaling. Through this unique role in cellular calcium dynamics and excitation-contraction coupling VDAC2 emerges as a plausible therapeutic target for heart failure.

[Infective prosthetic endocarditis following percutaneous edge-to-edge mitral valve repair - A Case-report of a successfully medically-treated Staphylococcus epidermidis endocarditis and a literature review]. / Endocardite infectieuse sur prothèse après implantation de Mitra-Clip ­ Cas d'un succès du traitement médical sur une endocardite à Staphylococcus epidermidis et revue de littérature.

During the last decade there has been a craze for the percutaneous edge-to-edge mitral valve repair technique with the Mitra-Clip device. This is an alternative treatment to mitral valve surgery for severe mitral regurgitation. In France, this device is aimed at poor candidates for mitral valve surgery. It involves intra-cardiac prosthetic material, which exposes them to the risk of bacterial endocarditis. The consequences of this infective disease can be dramatic, especially for these old patients who suffer from multiple comorbidities. It appears to be a rare but relatively unknown and potentially underestimated complication. The relative data remain scarce and consist of rare case-reports. We report an original case of a Methicilline-sensitive Staphylococcus epidermidis mitral endocarditis following the implantation of clips two months earlier. The patient was then successfully treated with antibiotics. Since the first Mitra-Clip implantation in 2003, only 19 cases of endocarditis have previously been reported. This article proposes a review of theses case-reports and a collection of their relevant clinical, echocardiographic and microbiological characteristics, the delivered therapies and their outcomes. These data contribute to a humble discussion around the main stakes of the disease, which are the prevention, the diagnosis, the involved bacteria's type, the prognosis and the treatments with a focus on the question of the recourse to surgical management.

[Surgical treatment of infective endocarditis: Surgical indications, complications, intrahospital and long-term mortality]. / Endocardites infectieuses opérées : indications chirurgicales, complications, mortalité intrahospitalière et à long terme.

BACKGROUND: In addition to medical treatment, half of the patients with infective endocarditis (IE) receive surgical treatment. Despite clear recommendations on the indications and the operating delays, the decision remains difficult and must take into consideration several factors. METHODS: A retrospective study was performed at Foch Hospital. All patients operated for IE between 2005 and 2018 were included. Patient characteristics, indications and operating delays, as well as intrahospital mortality, were noted. Patient follow-up was provided by phone calls. RESULTS: Fifty-two patients were operated on for IE between 2005 and 2018. The most frequent surgical indications were the presence of a massive symptomatic regurgitation, an uncontrolled infection and large vegetations with embolism. The average operative delay was 13.2 days with 56.5% of patients operated within the first 10 days. The most common postoperative complications were acute kidney injury (AKI) in 57.7% of cases, with 9.6% of dialysis, shock in 50% of cases, rhythm disorders in 40.4% of cases, infectious complications in 19.2% of cases, conductive disorders in 25% of cases, of which 17.3% require a definitive pacemaker implementation. The intrahospital mortality was 7.7% and the average length of hospital stay was 35 days. Survival at one year and 5 years was 95% and 85%, respectively. CONCLUSION: The indications and the operating delays were conformed to international recommendations. Intrahospital and long-term mortality rate was low.

Clinical epidemiology and outcomes of ventilator-associated pneumonia in critically ill adult patients: protocol for a large-scale systematic review and planned meta-analysis.

BACKGROUND: An increasing number of studies have investigated the clinical epidemiology and outcomes of ventilator-associated pneumonia (VAP) in intensive care units. However, these findings have not been clearly defined in broad subgroups of mechanically ventilated adults. Hence, this protocol for a systematic review and meta-analysis is designed to better understand the clinical and epidemiological features of VAP in these patient populations by establishing its overall prognosis of and risk factors for morbidity and mortality and to determine the differences in clinical and economic outcomes between VAP and non-VAP patients. METHODS: This present review will systematically search available full-text articles without date and language restrictions and indexed in PubMed, CENTRAL, CINAHL, Web of Science, and EMBASE databases. In addition, reference lists and citations of retrieved articles and relevant medical and nursing journals will be manually reviewed. Supplementary search in other databases involving trials, reviews, and grey literatures, including conference proceedings, theses, and dissertations, will be performed. Study investigators will be contacted to clarify missing or unpublished data. All prognostic studies meeting the pre-defined eligibility criteria will be included. The study selection, risk of bias assessment, data extraction, and grading of the quality of evidence will be carried out in duplicate, involving independent evaluation by two investigators with consensus or a third-party adjudication. The degree of inter-rater agreement will be calculated using the kappa statistic. For meta-analysis, dichotomous and continuous outcome measures will be pooled using odds ratios and standardized mean differences with 95% confidence intervals, respectively. The Mantel-Haenszel or inverse variance methods with random effects model will be used as a guide for analysis. The heterogeneity of each outcome measure will be assessed using both X2 and I2 statistics. In addition, sensitivity and subgroup analyses will be performed to ensure consistency of pooled results. The review protocol described herein is in accordance with the PRISMA-P standards. DISCUSSION: The investigation of the epidemiological profiles, prognostic factors, and outcomes associated with VAP is critical for the identification of high-risk groups of mechanically ventilated patients and evaluation of possible clinical endpoints. This may provide substantial links for improved VAP prevention practices targeting modifiable risk factors. Implications for future research directions are discussed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017048158.

Maximal strength training increases muscle force generating capacity and the anaerobic ATP synthesis flux without altering the cost of contraction in elderly.

Aging is associated with a progressive decline in skeletal muscle function, then leading to impaired exercise tolerance. Maximal strength training (MST) appears to be a practical and effective intervention to increase both exercise capacity and efficiency. However, the underlying physiological mechanisms responsible for these functional improvements are still unclear. Accordingly, the purpose of this study was to examine the intramuscular and metabolic adaptations induced by 8 weeks of knee-extension MST in the quadriceps of 10 older individuals (75 ±â€¯9 yrs) by employing a combination of molecular, magnetic resonance 1H-imaging and 31P-spectroscopy, muscle biopsies, motor nerve stimulation, and indirect calorimetry techniques. Dynamic and isometric muscle strength were both significantly increased by MST. The greater torque-time integral during sustained isometric maximal contraction post-MST (P = 0.002) was associated with increased rates of ATP synthesis from anaerobic glycolysis (PRE: 10 ±â€¯7 mM·min-1; POST: 14 ±â€¯7 mM·min-1, P = 0.02) and creatine kinase reaction (PRE: 31 ±â€¯10 mM·min-1; POST: 41 ±â€¯10 mM·min-1, P = 0.006) such that the ATP cost of contraction was not significantly altered. Expression of fast myosin heavy chain, quadriceps muscle volume, and submaximal cycling net efficiency were also increased with MST (P = 0.005; P = 0.03 and P = 0.03, respectively). Overall, MST induced a shift toward a more glycolytic muscle phenotype allowing for greater muscle force production during sustained maximal contraction. Consequently, some of the MST-induced improvements in exercise tolerance might stem from a greater anaerobic capacity to generate ATP, while the improvement in exercise efficiency appears to be independent from an alteration in the ATP cost of contraction.

[Ischemic stroke related to spontaneous]. / Accident vasculaire cérébral ischémique en rapport avec hématome coronaire spontané.

Cardiovascular disease in women is a particularly complex pathology especially in the youngest population. The clinical presentation of acute coronary syndromes is sometimes misleading and does not necessarily point to the potential presence of cardiac disease given the frequent absence of cardiovascular risks. Such complexity results in delayed diagnosis, which worsens the outcome of myocardial infarction and generates complications related to the absence of coronary revascularization. We report the case of a patient who suffered an (undiagnosed) apical myocardial infarction that went undetected and was complicated by a voluminous intraventricular thrombus with embolus migration in the cerebral circulation resulting in an ischemic accident. The combination of these two pathologies make their therapeutic management particularly difficult. As widely reported in the literature, the outcome of myocardial infarction in women is poorer than in their male counterparts for a number of reasons. We can assume that in the youngest patients, another physiopathological mechanism is often involved, namely, the occurrence of hematoma and spontaneous coronary dissection. Diagnosis is often difficult even with coronary angiography diagnosis. As shown in the case reported here, initial examination results, if not thoroughly analyzed, may be erroneously interpreted as normal. It is also likely that the presence of hematoma or coronary wall dissection without any plaque rupture may negatively influence the outcome owing to the implementation of inappropriate treatments. In conclusion, in patients presenting with an ischemic cerebral accident, meticulous cardiac examination must be performed even in young women with no cardiovascular risk factors given that the occurrence of hematoma or coronary dissection may contribute to the formation of mural thrombi in the setting of myocardial infarction. Cardiac MRI seems to be particularly effective in the diagnosis of myocardial infarction complicated by the presence of intracavitary thrombi.

Acinar Cell Carcinoma of the Pancreas: A Case Report.

Acinar cell carcinoma (ACC) of the pancreas is a very rare neoplasm. We report a case of pancreatic acinar cell carcinoma involving the uncinate process of the pancreas. A 45 year old man presented with a painful upper abdominal mass without any jaundice or weight loss. Computed Tomography (CT) and Magnetic Resonance Cholangio-Pancreatography (MRCP) indicated a mass lesion in the uncinate process of the pancreas. He underwent Whipple's procedure (Pancreaticoduodenectomy). Histological slides revealed features of Acinar cell carcinoma (ACC) in the uncinate process of the pancreas and a lymph node.

Sympathetic Signaling Reactivates Quiescent Disseminated Prostate Cancer Cells in the Bone Marrow.

Clinical observations have identified an association between psychologic stress and cancer relapse, suggesting that the sympathetic nervous system/norepinephrine (NE) plays a role in reactivation of dormant disseminated tumor cells (DTC) in the bone marrow niche. Here, the mechanism by which NE regulates prostate cancer DTCs in the marrow is explored. NE directly stimulated prostate cancer cell proliferation through ß2-adrenergic receptors (ADRB2). NE also altered prostate cancer proliferation in the marrow niche by indirectly downregulating the secretion of the dormancy inducing molecule growth arrest specific-6 (GAS6) expressed by osteoblasts. These observations were confirmed in cocultures of prostate cancer cells expressing the fluorescent ubiquitination-based cell-cycle reporters (FUCCI) and osteoblasts isolated from GAS6-deficient (GAS6-/-) animals. A novel ex vivo model system, using femurs harvested from GAS6+/+ or GAS6-/- mice, was used to confirm these results. As in coculture, when prostate cancer cells were injected into the marrow cavities of GAS6+/+ femurs, NE altered the prostate cancer cell cycle. However, NE had less of an impact on prostate cancer cells in femur explants isolated from GAS6-/- mice. Together, this study demonstrates that NE reactivates prostate cancer cell cycling through both a direct action on prostate cancer cells and indirectly on adjacent niche cells.Implications: Identification of mechanisms that target DTCs may provide novel therapeutic approaches to prevent or treat cancer metastases more effectively. Mol Cancer Res; 15(12); 1644-55. ©2017 AACR.

Endothelial Cell Autophagy Maintains Shear Stress-Induced Nitric Oxide Generation via Glycolysis-Dependent Purinergic Signaling to Endothelial Nitric Oxide Synthase.

OBJECTIVE: Impaired endothelial cell (EC) autophagy compromises shear stress-induced nitric oxide (NO) generation. We determined the responsible mechanism. APPROACH AND RESULTS: On autophagy compromise in bovine aortic ECs exposed to shear stress, a decrease in glucose uptake and EC glycolysis attenuated ATP production. We hypothesized that decreased glycolysis-dependent purinergic signaling via P2Y1 (P2Y purinoceptor 1) receptors, secondary to impaired autophagy in ECs, prevents shear-induced phosphorylation of eNOS (endothelial nitric oxide synthase) at its positive regulatory site S1117 (p-eNOSS1177) and NO generation. Maneuvers that restore glucose transport and glycolysis (eg, overexpression of GLUT1 [glucose transporter 1]) or purinergic signaling (eg, addition of exogenous ADP) rescue shear-induced p-eNOSS1177 and NO production in ECs with impaired autophagy. Conversely, inhibiting glucose transport via GLUT1 small interfering RNA, blocking purinergic signaling via ectonucleotidase-mediated ATP/ADP degradation (eg, apyrase), or inhibiting P2Y1 receptors using pharmacological (eg, MRS2179 [2'-deoxy-N6-methyladenosine 3',5'-bisphosphate tetrasodium salt]) or genetic (eg, P2Y1-receptor small interfering RNA) procedures inhibit shear-induced p-eNOSS1177 and NO generation in ECs with intact autophagy. Supporting a central role for PKCδT505 (protein kinase C delta T505) in relaying the autophagy-dependent purinergic-mediated signal to eNOS, we find that (1) shear stress-induced activating phosphorylation of PKCδT505 is negated by inhibiting autophagy, (2) shear-induced p-eNOSS1177 and NO generation are restored in autophagy-impaired ECs via pharmacological (eg, bryostatin) or genetic (eg, constitutively active PKCδ) activation of PKCδT505, and (3) pharmacological (eg, rottlerin) and genetic (eg, PKCδ small interfering RNA) PKCδ inhibition prevents shear-induced p-eNOSS1177 and NO generation in ECs with intact autophagy. Key nodes of dysregulation in this pathway on autophagy compromise were revealed in human arterial ECs. CONCLUSIONS: Targeted reactivation of purinergic signaling and PKCδ has strategic potential to restore compromised NO generation in pathologies associated with suppressed EC autophagy.

[Stress cardiac MRI in management of ischemic heart disease]. / La place de l'IRM cardiaque de stress dans la prise en charge de la cardiopathie ischémique.

Stress magnetic cardiac resonance imaging (MRI) development is in progress. Many cardiac imaging technics already known are completed by this safe radiation free exam with a short time acquisition (30minutes) and a good diagnostic performance in particular for patients with three vessels coronary artery diseases. Best indication concerns symptomatic patients unable to exercise with intermediate or high pretest probability. Pharmacological heart stress can be induced with vasodilatators or dobutamine to identify the presence and extent of myocardial ischemia, with high precision to guide coronary vessels revascularization. MRI gives many other interesting informations like heart anatomy, left ventricular function. Myocardial viability can be assessed with study of late gadolinium enhancement or analysis of contractile reserve with low dose of dobutamine.

Phytochemical Screening and Evaluation of Analgesic Activity of Oroxylum indicum.

We aimed to study phytochemical screening and analgesic activity of ethanol extract of Oroxylum indicum. The dried powder of the barks of the plant was extracted with 95% ethanol and was subjected to various phytochemical tests to ascertain the principle constituents contained in the extract. The result revealed the presence of alkaloids, flavonoids, tannins, glycosides in the ethanol extract of Oroxylum indicum. The extract was screened for analgesic activity by using hot plate, acetic acid-induced writhing and formalin test. The ethanol extract of the plant at two different doses (250 and 500 mg/kg) showed significant (P<0.05) analgesic effect in all test methods (hot plate, acetic acid-induced writhing and formalin). The analgesic activity was compared with a standard drug (ketorolac at 10 mg/kg). Based on the present findings and previous literature review it can be concluded that flavonoids and tannins might be responsible for the analgesic activity. We suggest that ethanol extract of Oroxylum indicum might have potential chemical constituents that could be used in the future for the development of novel analgesic agent.

Risky sex in rural America: longitudinal changes in a community-based cohort of methamphetamine and cocaine users.

BACKGROUND AND OBJECTIVES: This study examined the longitudinal associations between stimulant use and sexual behaviors. METHODS: Data are from a 3-year community-based study of 710 rural stimulant users. Past 30-day crack cocaine, powder cocaine, and methamphetamine use and sexual behaviors (any sex, inconsistent condom use, and multiple sexual partners) were assessed through in-person interviews every 6 months. RESULTS: GEE analyses revealed that the odds of having sex remained steady over time, with crack cocaine and methamphetamine use positively associated with having sex. The odds of multiple sexual partners declined, but the odds of inconsistent condom use remained steady over time. Crack cocaine use was positively associated with multiple sexual partners, whereas powder cocaine use was negatively associated with inconsistent condom use. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Many rural stimulant users could potentially benefit from safe sex educational programs. Such efforts could reduce the incidence of HIV and other STIs in rural America.

The effect of low and high plasma levels of insulin-like growth factor-1 (IGF-1) on the morphology of major organs: studies of Laron dwarf and bovine growth hormone transgenic (bGHTg) mice.

It is well known that somatotrophic/insulin signaling affects lifespan in experimental animals. To study the effects of insulin-like growth factor-1 (IGF-1) plasma level on the morphology of major organs, we analyzed lung, heart, liver, kidney, bone marrow, and spleen isolated from 2-year-old growth hormone receptor knockout (GHR-KO) Laron dwarf mice (with low circulating plasma levels of IGF-1) and 6-month-old bovine growth hormone transgenic (bGHTg) mice (with high circulating plasma levels of IGF-1). The ages of the two mutant strains employed in our studies were selected based on their overall ~50% survival (Laron dwarf mice live up to ~4 years and bGHTg mice up to ~1 year). Morphological analysis of the organs of long-living 2-year-old Laron dwarf mice revealed a lower biological age for their organs compared with normal littermates, with more brown adipose tissue (BAT) surrounding the main body organs, lower levels of steatosis in liver, and a lower incidence of leukocyte infiltration in different organs. By contrast, the organs of 6-month-old, short-living bGHTg mice displayed several abnormalities in liver and kidney and a reduced content of BAT around vital organs.

Variable-temperature ¹H-NMR studies on two C-glycosylflavones.

Two known C-glycosylflavones, swertisin and embinoidin, were isolated from the leaves of Anthurium aripoense, and characterized by room temperature 1D and 2D NMR experiments. At this temperature, the ¹H- and ¹³C-NMR spectra of these C-glycosylflavones revealed doubling of signals, which suggested the presence of two rotamers in solution. Variable-temperature (VT) ¹H-NMR studies supported this hypothesis. The T-ROESY data, in addition to the theoretical (MM2) calculations utilizing the Chem3D Pro software, confirmed the hypothesis that the two rotamers interchange via rotation about the C-glycosidic bond.

Surveying teens in school to assess the prevalence of problematic drug use.

BACKGROUND: Illicit drug use by school-aged teens can adversely affect their health and academic achievement. This study used a survey administered in schools to assess the prevalence of problematic drug use among teenagers in a Midwestern community. METHODS: Self-report data were collected from 11th- and 12th-grade students (N = 3974) in 16 school districts in the Dayton, Ohio, area. Students responded to a drug use survey that also included CRAFFT, a brief substance abuse screening instrument. Binomial and zero-inflated Poisson regressions were used to examine the association between CRAFFT scores and drug use practices, including abstinence. RESULTS: More than one third of students had CRAFFT scores suggestive of problematic use. Of these, 14.1% had scores suggesting drug dependence. Although alcohol, marijuana, and tobacco were the drugs most commonly used, an array of other drugs including opioids, benzodiazepines, stimulants, hallucinogens, and dextromethorphan were also commonly used. Higher CRAFFT scores were associated with a greater number of drugs used (p < .0001). Proportionately more 12th graders than 11th graders had CRAFFT scores indicating problems (p < .0001). Among 12th graders, boys were more likely than girls to have CRAFFT scores indicating dependence (p = .01). CONCLUSIONS: The results suggest that problematic drug use among high school students is more prevalent than has been recognized previously. CRAFFT can be used easily to assess the prevalence of problematic drug use among teenagers in school settings. CRAFFT results can also inform prevention and intervention activities, particularly if the CRAFFT instrument is paired with a drug use survey.

Physical victimization of rural methamphetamine and cocaine users.

Substance use and physical violence often coincide, but little has been published on the correlates associated with receipt of partner versus nonpartner physical violence for rural users of methamphetamine and/or cocaine. In this study, participants' substance use, depression and past-year physical victimization were assessed. In separate logistic regression models, received partner violence in females was associated with age; alcohol, cocaine, and methamphetamine abuse/dependence; and number of drugs used in the past 6 months. In males, received nonpartner violence was associated with age, cocaine abuse/dependence, and being Caucasian. Findings suggest a relationship between stimulant use and received violence among rural substance users and a need for victimization screenings in settings where such individuals seek health care.

Toxicity-structure activity evaluation of limonoids from Swietenia species on Artemia salina.

CONTEXT: Many plant extracts and compounds are being investigated for their cytotoxicity and hence their medicinal or therapeutic properties. Reports of toxicity studies with limonoid analogs have been sparse and have involved mainly crude extracts. In this study, individual natural limonoids have been isolated and their toxicity manipulated via semisynthesis. OBJECTIVE: The lethality of limonoid analogs from Swietenia macrophylla King and Swietenia aubrevilleana Stehlé & Cusin (Meliaceae) against Artemia salina Leach was determined. MATERIALS AND METHODS: Four known natural limonoids were isolated from the dry ground seeds of S. macrophylla and S. aubrevilleana, modified using acylation and hydrolysis reactions and tested in A. salina lethality assays at 1-400 ppm. A 50% lethal concentration (LC(50)) was determined by probit analysis. RESULTS: Higher levels of toxicity were achieved in most of the prepared analogs compared with the parent natural limonoids. The compound showing the highest toxicity with LC(50) 3.9 ppm was 3-O-benzoyl-3-detigloylisoswietenine (20). Other analogs with high toxicity were 6-O-benzoylswietenolide (7), 6-O-benzoylswietenine (17), and 3,6-O,O-dipropionylswietenolide (9), which showed LC(50) values of 4.3, 7.5, and 28.5 ppm, respectively. DISCUSSION AND CONCLUSIONS: Toxicity can be improved via semisynthesis. The compounds exhibiting high toxicity (low LC(50)) may be good candidates for cytotoxicity studies.

Effects of gamma radiation on a ventricular assist device and its percutaneous lead components.

A patient supported by a left ventricular assist device (LVAD) presented with an abdominal tumor requiring consolidative radiation therapy. To assess the effects of radiation therapy on the operation of the ventricular assist device (VAD) system and assure that the treatment would be safe for the patient with regard to the operation of the VAD system, sample equipment was irradiated and then tested for functionality. Changes in the mechanical properties of components of the percutaneous lead were measured. After testing, it was concluded that radiation therapy would not impede the operation of the pump or produce deleterious alterations of mechanical properties of the various system components. The patient underwent radiation therapy with a total dose of 2,000 cGy without evident complications. There were no observed effects on the LVAD operation nor any indication of alarms or malfunctions. Subsequently, the patient recovered adequate cardiac function for explant of the LVAD and the recovered components were also analyzed confirming the absence of alterations in material properties that would endanger patient safety.

The use of coupled HSQC spectra to aid in stereochemical assignments of molecules with severe proton spectral overlap.

INTRODUCTION: A simple glycoside with only 13 carbons exhibited extensive overlapping of four of the glycosidic protons, causing extreme difficulty in the determination of the stereochemistry of the pyranose unit. However, acquisition of a high-resolution coupled heteronuclear single-quantum coherence (HSQC) spectrum overcame this problem. This spectrum provides a useful method for determining vicinal proton coupling constants between strongly coupled protons. OBJECTIVE: To show the potential of high-resolution coupled HSQC spectra in overcoming spectral overlap. METHODOLOGY: The sample was obtained by methanol extraction, followed by fractionation and column chromatography of the dried leaves of Montrichardia arborescens (Araceae). NMR spectra were obtained on 1.5 mg of sample dissolved in 120 µL of CD3OD containing 0.1% trimethylsilyl (TMS) as internal standard. A gradient-selected HSQC spectrum was obtained using standard Varian library pulse sequences in phase sensitive mode. The high-resolution coupled HSQC spectrum focused on the saccharide region with a 1025 Hz ¹H spectral window, a 6300 Hz ¹³C spectral window, 1024 data points, a 0.3 Hz relaxation delay, 384 time increments (linear predicted to 4096), and 80 scans per time increment. RESULTS: The use of a high-resolution coupled HSQC spectrum allowed determination of the coupling patterns of the various pyranose protons with sufficient accuracy. This enabled completion of the assignments and identification of the pyranose unit as glucose. CONCLUSION: The study has shown the effectiveness of the use of a high-resolution coupled HSQC spectrum in the assignment of molecules with severe spectral overlap.