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1.
J Am Coll Health ; 70(3): 654-659, 2022 04.
Article in English | MEDLINE | ID: mdl-32569507

ABSTRACT

Needle anxiety symptoms are prevalent among college students and predict lack of engagement in student health initiatives including influenza immunization programs. Most do not seek treatment for their anxiety. Objective: To develop and test a peer-delivered, brief motivational interview to promote help-seeking behaviors among college students with needle anxiety symptoms. Participants/Methods: 61 university students who reported needle anxiety symptoms and having avoided medical situations involving needles in the last year were randomized to intervention or control conditions. Analyses compared self-reported help seeking behaviors at three months post-intervention. Results: Intervention group participants were more than twice as likely to report help-seeking behavior at follow up (IR = 2.41; 95%CI = 1.29, 4.50; p=.006) than the control group. Participants also endorsed high levels of satisfaction with the intervention. Conclusions: This pilot intervention appears acceptable and feasible to implement using peers in the college setting. There is preliminary evidence for efficacy, with larger-scale replication needed.


Subject(s)
Help-Seeking Behavior , Students , Anxiety/therapy , Humans , Needles , Universities
2.
Rev Sci Instrum ; 92(2): 023307, 2021 Feb 01.
Article in English | MEDLINE | ID: mdl-33648074

ABSTRACT

An apparatus allowing continuous acquisition of thickness measurements during electropolishing of superconducting cavities is described. The instrument is based on the ultrasound thickness measurement technique and allows the connection of up to six probes. The apparatus has been employed to monitor the surface treatment of PIP-II low beta single cell prototypes developed and manufactured by LASA-INFN and specifically to measure surface removal at different points of interest on the cavity surface. The apparatus facilitated the development and optimization of electropolishing parameters for incorporation into the cavity manufacturing process.

3.
Eur J Clin Microbiol Infect Dis ; 39(4): 749-751, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31858355

ABSTRACT

Community-acquired pneumonia (CAP) is one of the major causes of morbidity, mortality and hospitalization, and S. pneumoniae is the most frequently isolated etiologic agent. The pneumococcal urinary antigen test (PUAT) is among the recommended methods to identify the causative agent in CAP patients. A novel PUAT (IMMUNOCATCHTMStreptococcus pneumoniae) was compared with the Uni-GoldTMS. pneumoniae assay routinely used in our laboratory and with the widely used BinaxNOW® S. pneumoniae antigen card. A total of 218 (183 freshly harvested and 35 frozen) urine samples (US) submitted for the detection of pneumococcal urinary antigen (PUAT) between December 2016 and November 2018 were evaluated. A number of 160 negative and 41 positive concordant results were scored for all the three assays. A total of 17 US gave discrepant results. The sensitivity and specificity of Immunocatch compared with Uni-Gold were 73.2% and 98.8%, respectively, and compared with BinaxNOW were 97.6% and 98.8%, respectively. The overall percent agreement (OPA) and the Cohen's kappa coefficient between the Immunocatch and the Uni-Gold resulted 92.2% and 0.78%, respectively, and compared with BinaxNOW were 98.6% and 0.95%, respectively. These performances suggest that the novel Immunocatch S. pneumoniae test is a useful tool for qualitative detection of S. pneumoniae capsular antigen in US.


Subject(s)
Antigens, Bacterial/urine , Clinical Laboratory Techniques/standards , Pneumonia, Pneumococcal/diagnosis , Pneumonia, Pneumococcal/urine , Reagent Kits, Diagnostic/standards , Clinical Laboratory Techniques/methods , Community-Acquired Infections/diagnosis , Community-Acquired Infections/microbiology , Community-Acquired Infections/urine , Humans , Sensitivity and Specificity , Streptococcus pneumoniae
4.
J Clin Microbiol ; 57(8)2019 08.
Article in English | MEDLINE | ID: mdl-31092595

ABSTRACT

Legionnaires' disease (LD) refers to a serious form of acute pneumonia caused by Legionella species. LD can be difficult to diagnose because the signs and symptoms are nonspecific, and therefore a rapid laboratory diagnosis is of paramount importance. In this study, a recently introduced immunochromatographic test (Immunocatch Legionella; Eiken Chemical Co., Ltd.) for Legionella pneumophila (serogroup 1) urinary antigen detection was compared with the Sofia Legionella fluorescent immunoassay (FIA) (Quidel) (routinely used in our laboratory) and with the widely used BinaxNOW Legionella assay (Alere). A total of 248 urine samples (60 frozen and 188 fresh) were evaluated. All of the samples were collected from patients with high clinical suspicion of Legionnaires' disease. The three assays were performed simultaneously according to the manufacturers' instructions. A total of 180 concordant negative and 66 concordant positive results were obtained. Only 2 discrepant results were registered. The sensitivity and specificity of Immunocatch compared with Sofia were, respectively, 98.5% and 99.4%. Cohen's kappa coefficient and overall percent agreement between Immunocatch and Sofia were also calculated and resulted in, respectively, 0.97 and 99.2%. These performances suggest that the Immunocatch test is a useful tool for Legionella pneumophila (serogroup 1) urinary antigen detection.


Subject(s)
Antigens, Bacterial/urine , Fluorescent Antibody Technique , Immunoassay/standards , Legionnaires' Disease/diagnosis , Legionnaires' Disease/urine , Antigens, Bacterial/immunology , Community-Acquired Infections/diagnosis , Community-Acquired Infections/microbiology , Community-Acquired Infections/urine , Humans , Immunoassay/methods , Legionella pneumophila/immunology , Sensitivity and Specificity , Serogroup
5.
New Microbes New Infect ; 23: 39-43, 2018 May.
Article in English | MEDLINE | ID: mdl-29556408

ABSTRACT

Shewanella algae are Gram-negative, nonfermentative, motile bacilli, classified in the genus Shewanella in 1985. These environmental bacteria are occasionally identified in human infections, with a relatively strong association with exposure to seawater during warm seasons. This report describes a case series of 17 patients with infection correlated to S. algae in the coastal area of Romagna, Italy, from 2013 to 2016. The types of infection included otitis, pneumonia, sepsis and soft tissue (wound). Exposure to the marine environment during hot months was confirmed in 12 of 17 patients. An apparent correlation between increased severity of infection and patient age was also observed.

6.
J Neurophysiol ; 117(4): 1831-1840, 2017 04 01.
Article in English | MEDLINE | ID: mdl-28228584

ABSTRACT

This study tested the hypothesis that high cardiorespiratory fitness (peak oxygen uptake) preserves the cortical circuitry associated with cardiac arousal during exercise in middle- to older-aged individuals. Observations of changes in heart rate (HR) and in cortical blood oxygenation level-dependent (BOLD) images were made in 52 healthy, active individuals (45-73 yr; 16 women, 36 men) across a range of fitness (26-66 ml·kg-1·min-1). Seven repeated bouts of isometric handgrip (IHG) at 40% maximal voluntary contraction force were performed with functional magnetic resonance imaging at 3 T, with each contraction lasting 20 s and separated by 40 s of rest. HR responses to IHG showed high variability across individuals. Linear regression revealed that cardiorespiratory fitness was not a strong predictor of the HR response (r2 = 0.09). In a region-of-interest analysis both the IHG task and the HR time course correlated with increased cortical activation in the bilateral insula and decreased activation relative to baseline in the anterior and posterior cingulate and medial prefrontal cortex (MPFC). t-Test results revealed greater deactivation at the MPFC with higher fitness levels beyond that of guideline-based activity. Therefore, whereas high cardiorespiratory fitness failed to affect absolute HR responses to IHG in this age range, a select effect was observed in cortical regions known to be associated with cardiovascular arousal.NEW & NOTEWORTHY Our first observation suggests that fitness does not strongly predict the heart rate (HR) response to a volitional handgrip task in middle- to older-aged adults. Second, the BOLD response associated with the handgrip task, and with the HR time course, was associated with response patterns in the cortical autonomic network. Finally, whereas high cardiorespiratory fitness failed to affect absolute HR responses to isometric handgrip in this age range, a select effect was observed in cortical regions known to be associated with cardiovascular arousal, beyond that achieved through healthy active living.


Subject(s)
Brain/diagnostic imaging , Brain/physiology , Cardiorespiratory Fitness/physiology , Exercise/physiology , Heart Rate/physiology , Aged , Blood Pressure/physiology , Brain Mapping , Electrocardiography , Exercise Test , Female , Hand Strength , Humans , Image Processing, Computer-Assisted , Linear Models , Magnetic Resonance Imaging , Male , Middle Aged , Oxygen/blood , Volition/physiology
7.
Am J Physiol Regul Integr Comp Physiol ; 311(5): R957-R963, 2016 11 01.
Article in English | MEDLINE | ID: mdl-27733385

ABSTRACT

We tested the hypothesis that sympathetic responses to baroreceptor unloading may be affected by circulating sex hormones. During lower body negative pressure at -30, -60, and -80 mmHg, muscle sympathetic nerve activity (MSNA), heart rate, and blood pressure were recorded in women who were taking (n = 8) or not taking (n = 9) hormonal contraceptives. All women were tested twice, once during the low-hormone phase (i.e., the early follicular phase of the menstrual cycle and the placebo phase of hormonal contraceptive use), and again during the high-hormone phase (i.e., the midluteal phase of the menstrual cycle and active phase of contraceptive use). During baroreceptor unloading, the reductions in stroke volume and resultant increases in MSNA and total peripheral resistance were greater in high-hormone than low-hormone phases in both groups. When normalized to the fall in stroke volume, increases in MSNA were no longer different between hormone phases. While stroke volume and sympathetic responses were similar between women taking and not taking hormonal contraceptives, mean arterial pressure was maintained during baroreceptor unloading in women not taking hormonal contraceptives but not in women using hormonal contraceptives. These data suggest that differences in sympathetic activation between hormone phases, as elicited by lower body negative pressure, are the result of hormonally mediated changes in the hemodynamic consequences of negative pressure, rather than centrally driven alterations to sympathetic regulation.


Subject(s)
Blood Pressure/physiology , Gonadal Steroid Hormones/blood , Heart Rate/physiology , Lower Body Negative Pressure , Pressoreceptors/physiology , Sympathetic Nervous System/physiology , Adult , Blood Pressure/drug effects , Contraceptives, Oral, Hormonal/administration & dosage , Contraceptives, Oral, Hormonal/pharmacology , Female , Follicular Phase/drug effects , Follicular Phase/physiology , Heart Rate/drug effects , Humans , Luteal Phase/drug effects , Luteal Phase/physiology , Pressoreceptors/drug effects , Sympathetic Nervous System/diagnostic imaging
8.
New Microbes New Infect ; 9: 54-5, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26862436

ABSTRACT

The first isolation of Catabacter hongkongensis in Italy is reported. Pleomorphic Gram-positive rods were grown in blood cultures from samples obtained from a 55-year-old patient admitted to the intensive care unit with sepsis after he experienced massive thoracic and abdominal trauma. The identification was obtained by amplification and sequencing of the 16S rRNA gene.

9.
J Food Sci Technol ; 52(7): 4360-8, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26139901

ABSTRACT

The objective of this work was to evaluate the effect of adding different starches (native and modified) on the physicochemical, sensory, structural and microbiological characteristics of low-fat chicken mortadella. Two formulations containing native cassava and regular corn starch, coded CASS (5.0 % of cassava starch) and CORN (5.0 % of regular corn starch), and one formulation produced with physically treated starch coded as MOD1 (2.5 % of Novation 2300) and chemically modified starch coded as MOD2 (2.5 % of Thermtex) were studied. The following tests were performed: physicochemical characterization (moisture, ash, protein, starch and lipid contents, and water activity); cooling, freezing and reheating losses; texture (texture profile test); color coordinates (L*, a*, b*, C and h); microbiological evaluation; sensory evaluation (multiple comparison and preference test); and histological evaluation (light microscopy). There was no significant difference (p > 0.05) for ash, protein, cooling loss, cohesiveness or in the preference test for the tested samples. The other evaluated parameters showed significant differences (p < 0.05). Histological study allowed for a qualitative evaluation between the physical properties of the food and its microscopic structure. The best results were obtained for formulation MOD2 (2.5 % Thermtex). The addition of modified starch resulted in a better performance than the native starch in relation to the evaluated technological parameters, mainly in relation to reheating losses, which demonstrated the good interaction between the modified starch in the structure of the product and the possibility of the application of this type of starch in other types of functional meat products.

10.
Am J Physiol Heart Circ Physiol ; 308(6): H664-71, 2015 Mar 15.
Article in English | MEDLINE | ID: mdl-25527774

ABSTRACT

This study aimed to examine the effects of sex (males vs. females) and sex hormones (menstrual cycle phases in women) on sympathetic responsiveness to severe chemoreflex activation in young, healthy individuals. Muscle sympathetic nerve activity (MSNA) was measured at baseline and during rebreathing followed by a maximal end-inspiratory apnea. In women, baseline MSNA was greater in the midluteal (ML) than early-follicular (EF) phase of the menstrual cycle. Baseline MSNA burst incidence was greater in men than women, while burst frequency and total MSNA were similar between men and women only in the ML phase. Chemoreflex activation evoked graded increases in MSNA burst frequency, amplitude, and total activity in all participants. In women, this sympathoexcitation was greater in the EF than ML phase. The sympathoexcitatory response to chemoreflex stimulation of the EF phase in women was also greater than in men. Nonetheless, changes in total peripheral resistance were similar between sexes and menstrual cycle phases. This indicates that neurovascular transduction was attenuated during the EF phase during chemoreflex activation, thereby offsetting the exaggerated sympathoexcitation. Chemoreflex-induced increases in mean arterial pressure were similar across sexes and menstrual cycle phases. During acute chemoreflex stimulation, reduced neurovascular transduction could provide a mechanism by which apnea-associated morbidity might be attenuated in women relative to men.


Subject(s)
Chemoreceptor Cells/metabolism , Hypercapnia/metabolism , Hypoxia/metabolism , Menstrual Cycle/metabolism , Muscle, Skeletal/innervation , Reflex , Stress, Physiological , Sympathetic Nervous System/physiopathology , Action Potentials , Adult , Biomarkers/blood , Female , Hemodynamics , Humans , Hypercapnia/blood , Hypercapnia/physiopathology , Hypoxia/blood , Hypoxia/physiopathology , Male , Menstrual Cycle/blood , Sex Factors , Time Factors , Young Adult
11.
Brain Res ; 1538: 104-15, 2013 Nov 13.
Article in English | MEDLINE | ID: mdl-24076209

ABSTRACT

Cardiovascular arousal correlates to activity within the medial prefrontal cortex (MPFC). Additional evidence provides anatomical and functional links between the MPFC and hippocampus (HC). This study tested the hypothesis that the MPFC and HC form a sub-network associated with rapid heart rate (HR) responses to volitional effort. Primary analyses were performed on 29 individuals (18 males) ranging from 21 to 80 years of age, who produced a HR response >3bpm to an isometric handgrip (IHG) task. HR and cortical activity were recorded using functional magnetic resonance imaging with blood oxygen level-dependent contrast. The average change in HR from baseline was 6bpm ±2. Activity in the MPFC and left HC was reduced relative to baseline in all subjects when correlated with the HR time course. Measures of connectivity demonstrated that the MPFC engaged in significantly stronger functional connectivity to the left HC during a 40% IHG task. Effective connectivity revealed a directionality of influence from the MPFC to the left HC. A second group (n=15) of individuals without a HR response (~1bpm) to IHG were studied post-hoc and these individuals showed no deactivation in either the MPFC or left HC. These results suggest the presence of a MPFC-HC axis that participates in the neurally-mediated HR response to exercise.


Subject(s)
Heart Rate/physiology , Hippocampus/physiology , Prefrontal Cortex/physiology , Adult , Aged , Aged, 80 and over , Brain Mapping , Female , Hand Strength/physiology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Nerve Net/physiology , Young Adult
12.
J Appl Physiol (1985) ; 115(10): 1415-22, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24009009

ABSTRACT

Hormone fluctuations in women may influence muscle sympathetic nerve activity (MSNA) in a manner dependent on the severity of the sympathoexcitatory stimulus. This study examined MSNA patterns at rest and during chemoreflex stimulation in low- (LH) vs. high-hormone (HH) phases of contraceptive use in healthy young women (n = 7). We tested the hypothesis that MSNA would be greater in the HH phase at baseline and in response to chemoreflex stimulation. MSNA recordings were obtained through microneurography in LH and HH at baseline, during rebreathing causing progressive hypoxia and hypercapnia, and during a hypercapnic-hypoxic end-inspiratory apnea. Baseline MSNA burst incidence (P = 0.03) and burst frequency (P = 0.02) were greater in the HH phase, while MSNA burst amplitude distributions and hemodynamic measures were similar between phases. Rebreathing elicited increases in all MSNA characteristics from baseline (P < 0.05), but was not associated with hormone phase-dependent changes to MSNA patterns. Apnea data were considered in two halves, both of which caused large increases in all MSNA variables from baseline in each hormone phase (P < 0.01). Increases in burst incidence and frequency were greater in LH during the first half of the apnea (P = 0.03 and P = 0.02, respectively), while increases in burst amplitude and total MSNA were greater in LH during the second half of the apnea (P < 0.05). These results indicate that change in hormone phase brought on through use of hormonal contraceptives influences MSNA patterns such that baseline MSNA is greater in the HH phase, but responses to severe chemoreflex stimulation are greater in the LH phase.


Subject(s)
Chemoreceptor Cells/drug effects , Contraceptives, Oral, Hormonal/administration & dosage , Muscle, Skeletal/innervation , Peroneal Nerve/drug effects , Reflex/drug effects , Sympathetic Nervous System/drug effects , Action Potentials , Adult , Age Factors , Apnea/metabolism , Apnea/physiopathology , Chemoreceptor Cells/metabolism , Drug Administration Schedule , Female , Hemodynamics , Humans , Hypercapnia/metabolism , Hypercapnia/physiopathology , Hypoxia/metabolism , Hypoxia/physiopathology , Peroneal Nerve/metabolism , Peroneal Nerve/physiopathology , Respiration , Sympathetic Nervous System/metabolism , Sympathetic Nervous System/physiopathology , Time Factors , Young Adult
13.
Monaldi Arch Chest Dis ; 78(1): 29-33, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22928401

ABSTRACT

BACKGROUND: To evaluate the psychological characteristics of coronary heart disease (CHD) patients after coronary artery bypass grafting (CABG) by cluster analysis of Minnesota Multiphasic Personality Inventory (MMPI-2) questionnaires and to assess the impact of the profiles obtained on long-term outcome. METHODS: 229 CHD patients admitted to cardiac rehabilitation filled in self-administered MMPI-2 questionnaires early after CABG. We assessed the relation between MMPI-2 profiles derived by cluster analysis, clinical characteristics and outcome at 3-year follow-up. RESULTS: Among the 215 patients (76% men, median age 66 years) with valid criteria in control scales, we identified 3 clusters (G) with homogenous psychological characteristics: G1 patients (N = 75) presented somatoform complaints but overall minimal psychological distress. G2 patients (N=72) presented type D personality traits. G3 subjects (N=68) showed a trend to cynicism, mild increases in anger, social introversion and hostility. Clusters overlapped for clinical characteristics such as smoking (G1 21%, G2 24%, G3 24%, p ns), previous myocardial infarction (G1 43%, G2 47%, G3 49% p ns), LV ejection fraction (G1 60 [51-60]; G2 58 [49-60]; G3 60 [55-60], p ns), 3-vessel-disease prevalence (G1 69%, G2 65%, G3 71%, p ns). Three-year event rates were comparable (G1 15%; G2 18%; G3 15%) and Kaplan-Meier curves overlapped among clusters (p ns). CONCLUSIONS: After CABG, the interpretation of MMPI-2 by cluster analysis is useful for the psychological and personological diagnosis to direct psychological assistance. Conversely, results from cluster analysis of MMPI-2 do not seem helpful to the clinician to predict long term outcome.


Subject(s)
Coronary Artery Bypass/psychology , MMPI , Aged , Cluster Analysis , Female , Humans , Male , Middle Aged , Time Factors , Treatment Outcome
14.
Neuroscience ; 164(2): 530-40, 2009 Dec 01.
Article in English | MEDLINE | ID: mdl-19665519

ABSTRACT

Cholesterol is required in the brain for synaptogenesis and its turnover is critical for cerebral functions. Several proteins involved in cholesterol handling and metabolism are transcriptionally regulated by the nuclear liver X receptor (LXR) alpha and beta. Sterol 27-hydroxylase (CYP27) is a ubiquitously expressed enzyme involved in cholesterol metabolism. Notably, its deficiency causes a disease characterized by progressive neurologic impairment. With the final goal to understand the pathophysiological role of CYP27A1 in the CNS, we studied the expression pattern of Cyp27a1 and other related genes in primary cultures of rat glia and neurons. Secondly, given the pivotal role of LXR in the regulation of cholesterol homeostasis, we investigated the effects of its activation on the expression of Cyp27a1.We found that primary astrocytes express different sterol hydroxylases and are able to uptake exogenous 27-hydroxycholesterol. We found that both microglia and astrocytes express preferentially Lxrbeta. However, despite this similarity, we observed cell-specific responsiveness of known and novel (including Cyp27a1) target genes to LXR activation. The increase of mRNA and protein levels in treated astrocytes is paralleled by transactivation of the proximal Cyp27a1 promoter in transfected astrocytes. We suggest that the astrocyte-restricted up-regulation of Cyp27a1 may be ascribable to differential expression of transcriptional co-activators. Given the role of astrocytes in maintaining brain homeostasis, we hypothesize that impairment of CYP27 activity in these cells may alter critical features of the astrocytes, from the handling and delivery of cholesterol to neurons to the release of signaling molecules.


Subject(s)
Brain/metabolism , Cholestanetriol 26-Monooxygenase/metabolism , Microglia/metabolism , Neuroglia/metabolism , Orphan Nuclear Receptors/metabolism , Animals , Brain/enzymology , Cells, Cultured , Cholestanetriol 26-Monooxygenase/genetics , Cholesterol/metabolism , Gene Expression Regulation , Homeostasis/genetics , Hydroxycholesterols/metabolism , Liver X Receptors , Microglia/enzymology , Neuroglia/enzymology , Neurons/enzymology , Neurons/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Steroid Hydroxylases/metabolism , Transcription, Genetic
15.
Am J Transplant ; 7(9): 2133-9, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17640314

ABSTRACT

Little information is available about the long-term outcome of renal transplantation in patients with systemic vasculitis (SV). We compared the outcomes of 19 renal transplant recipients with SV with those of 38 controls matched for time of transplantation, age, gender and source of donor. The mean post-transplant follow-up was 58 +/- 57 months for vasculitic patients and 61 +/- 49 months for controls. The actuarial 10-year patient survival was 87% in vasculitic patients and 90% in controls, death-censored graft survival were 84% and 100%, respectively. The risks of acute and chronic rejection, and arterial hypertension were not significantly different between the two groups. Infection was significantly more frequent in vasculitic patients (74% vs. 34%; p = 0.01). Seven patients (36.8%) had a recurrence of vasculitis in mean 45 months after renal transplant (0.076/patients/year). After recurrence, one patient had an irreversible humoral rejection, another died from hemophagocytosis and another restarted dialysis 1 year later. Long-term patient and renal allograft survival in vasculitic patients was good. Although graft function recovered in most relapsers after reinforcement of immunosuppression, one patient died and two lost graft function.


Subject(s)
Kidney Failure, Chronic/surgery , Kidney Transplantation , Vasculitis/surgery , Biopsy , Female , Follow-Up Studies , Graft Survival , Humans , Kidney/pathology , Kidney Failure, Chronic/complications , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Time Factors , Vasculitis/etiology , Vasculitis/pathology
16.
Nutr Metab Cardiovasc Dis ; 12(1): 24-8, 2002 Feb.
Article in English | MEDLINE | ID: mdl-12125226

ABSTRACT

BACKGROUND AND AIM: It has been reported that atorvastatin increases high-density lipoprotein cholesterol (HDL-C) more in patients with low than in those with high baseline HDL-C levels. This may have a biological explanation, but also suggests a statistical artifact known as the regression to the mean. METHODS AND RESULTS: Atorvastatin 10 mg/day led to a 4% increase in HDL-C after two months in 67/121 patients with hypercholesterolemia (55%), who had lower baseline HDL-C levels than the patients in whom HDL-C did not increase. In the patients with baseline HDL-C below the median, HDL-C significantly increased whereas no change was observed in patients with baseline HDL-C above the median. The correlation coefficient between pre- and post-treatment HDL-C was 0.84, thus suggesting a regression to the mean. However, the regression artifact did not entirely explain the increase in HDL-C in patients with low baseline HDL-C or the lack of an increase in those with high baseline HDL-C. The adjusted mean increase was 5.4% in patients with low pretreatment HDL-C, and 2.4% in the patients with high pretreatment HDL-C. Multiple regression analysis with the changes in HDL-C as the dependent variable showed that baseline HDL-C and the changes in serum triglycerides independently contributed to the change in HDL-C levels. CONCLUSIONS: Atorvastatin 10 mg/day increases HDL-C more in patients with low pretreatment HDL-C levels, an effect that seems to be related to the hypotriglyceridemic activity of the drug.


Subject(s)
Anticholesteremic Agents/therapeutic use , Cholesterol, HDL/drug effects , Heptanoic Acids/therapeutic use , Hypercholesterolemia/drug therapy , Pyrroles/therapeutic use , Adult , Aged , Anticholesteremic Agents/pharmacology , Atorvastatin , Cholesterol, HDL/blood , Coronary Disease/blood , Coronary Disease/drug therapy , Female , Heptanoic Acids/pharmacology , Humans , Hypercholesterolemia/blood , Male , Middle Aged , Pyrroles/pharmacology , Regression Analysis , Triglycerides/blood
17.
Bioorg Med Chem Lett ; 11(17): 2393-6, 2001 Sep 03.
Article in English | MEDLINE | ID: mdl-11527739

ABSTRACT

Structure-activity studies associated with the salicylic acid-derived inhibitor of influenza fusion, BMY-27709, were examined using a parallel synthesis approach. This SAR survey led to the discovery of potent influenza inhibitory activity in a series of aromatic amides and thioamides derived from 1,3,3-trimethyl-5-hydroxycyclohexylmethylamine. Select compounds were characterized as inhibitors of the H1 subtype of influenza A viruses that act by preventing the pH-induced fusion process, thereby blocking viral entry into host cells. In a plaque-reduction assay, the most potent inhibitors displayed EC(50) values of 0.02-0.14 microg/mL.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Influenza A virus/drug effects , Thioamides/chemistry , Thioamides/pharmacology , Amines/chemistry , Cells, Cultured/virology , Drug Evaluation, Preclinical , Hemolysis/drug effects , Humans , Influenza A virus/pathogenicity , Magnetic Resonance Spectroscopy , Membrane Fusion/drug effects , Molecular Structure , Quinolizines/chemistry , Quinolizines/pharmacology , Stereoisomerism , Structure-Activity Relationship
18.
Clin Ther ; 23(6): 851-7, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11440285

ABSTRACT

BACKGROUND: Simvastatin 40 to 80 mg/d has been found to increase high-density lipoprotein cholesterol (HDL-C) levels significantly more than atorvastatin at equipotent doses (ie, 20-80 mg/d). Data on the effects of lower doses of the 2 drugs on HDL-C levels are conflicting. OBJECTIVE: The purpose of this study was to investigate the effects of simvastatin 20 mg/d and atorvastatin 10 mg/d on HDL-C levels in patients with hypercholesterolemia. METHODS: Patients with primary hypercholesterolemia (total cholesterol [TC] >250 mg/dL) who were not taking any lipid-lowering agents and who were following a low-fat diet were randomized to receive 1 of 2 treatments: simvastatin 20 mg/d or atorvastatin 10 mg/d. Serum TC, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and HDL-C levels were measured using standard methods after 2 months of therapy. In a secondary analysis, lipids and lipoprotein cholesterol were measured after 1 year in patients who continued treatment. RESULTS: Of the 240 patients enrolled (108 men and 132 women; age range, 23-77 years, mean [SEM] 56.7 [0.69]), 235 completed the study. After 2 months of therapy, TC, LDL-C, and serum TG levels decreased significantly versus baseline in both groups (P < 0.001), with no significant differences between treatment groups. HDL-C levels increased by 9.0% (P < 0.001 vs baseline) in the simvastatin group and by 4.3% (P < 0.02) in the atorvastatin group. The difference between the 2 groups in the percentage increase in HDL-C was statistically significant (P < 0.05). In 113 patients who continued treatment, HDL-C levels at 1 year were still significantly higher than baseline levels in the simvastatin group (6.3%, P = 0.034), but not in the atorvastatin group (2.8%, P = 0.587). CONCLUSIONS: The findings from this study suggest that the HDL-C-increasing effect of simvastatin 20 mg is significantly greater than that of atorvastatin 10 mg. Since increasing HDL-C levels is thought to lower the risk for atherosclerosis and coronary heart disease, these results warrant further investigation.


Subject(s)
Anticholesteremic Agents/therapeutic use , Cholesterol, HDL/blood , Heptanoic Acids/therapeutic use , Hypercholesterolemia/drug therapy , Pyrroles/therapeutic use , Simvastatin/therapeutic use , Adult , Aged , Anticholesteremic Agents/administration & dosage , Anticholesteremic Agents/adverse effects , Atorvastatin , Female , Heptanoic Acids/administration & dosage , Heptanoic Acids/adverse effects , Humans , Hypercholesterolemia/blood , Lipids/blood , Male , Middle Aged , Pyrroles/administration & dosage , Pyrroles/adverse effects , Simvastatin/administration & dosage , Simvastatin/adverse effects
19.
Bioorg Med Chem Lett ; 10(15): 1649-52, 2000 Aug 07.
Article in English | MEDLINE | ID: mdl-10937716

ABSTRACT

Structural variation of the quinolizidine heterocycle of the influenza fusion inhibitor BMY-27709 was examined by several topological dissections in order to illuminate the critical features of the ring system. This exercise resulted in the identification of a series of synthetically more accessible decahydroquinolines that retained the structural elements of BMY-27709 important for antiviral activity. The 2-methyl-cis-decahydroquinoline 6f was the most potent influenza inhibitor identified that demonstrated an EC50 of 90 ng/mL in a plaque reduction assay.


Subject(s)
Antiviral Agents/pharmacology , Membrane Fusion/drug effects , Orthomyxoviridae/drug effects , Quinolizines/pharmacology , Salicylamides/pharmacology , Animals , Antiviral Agents/chemistry , Cell Line , Dogs , Orthomyxoviridae/physiology , Quinolizines/chemistry , Salicylamides/chemistry
20.
Eur J Clin Pharmacol ; 55(7): 499-502, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10501818

ABSTRACT

OBJECTIVES: The main effect of statins is the decrease of serum level of low-density lipoprotein (LDL) cholesterol, due to the inhibition of intracellular cholesterol biosynthesis which brings about an upregulation of LDL receptors. A minor effect is the decrease of serum triglycerides. The present study was undertaken to verify whether all statins are effective in reducing serum triglycerides and whether their effect on triglycerides is related to the LDL cholesterol lowering activity. METHODS: Of 197 hypercholesterolaemic patients on stable low-fat low-cholesterol diet, 49 were put on atorvastatin 10 mg per day, 48 on fluvastatin 40 mg per day, 50 on pravastatin 20 mg per day and 50 on simvastatin 10 mg per day. RESULTS: After 2 months, mean percentage change in serum triglycerides and LDL cholesterol resulted to be significantly different among the four treatment groups, whereas the ratio between the percentage decrease in serum triglycerides and that of LDL cholesterol (Deltatriglyceride/DeltaLDL cholesterol ratio) was not significantly different. Only baseline serum triglycerides resulted to be significantly associated with Deltatriglycerides/DeltaLDL cholesterol ratio. All statins are then effective in decreasing triglyceride levels. CONCLUSION: The lack of a significant difference in Deltatriglycerides/DeltaLDL cholesterol ratio among the treatment groups suggests that the more effective the statin is in decreasing LDL cholesterol, the more it will also be in decreasing serum triglycerides.


Subject(s)
Anticholesteremic Agents/therapeutic use , Hypercholesterolemia/drug therapy , Triglycerides/blood , Adult , Aged , Analysis of Variance , Atorvastatin , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, HDL/drug effects , Cholesterol, LDL/blood , Cholesterol, LDL/drug effects , Fatty Acids, Monounsaturated/therapeutic use , Female , Fluvastatin , Heptanoic Acids/therapeutic use , Humans , Hypercholesterolemia/blood , Indoles/therapeutic use , Male , Middle Aged , Pravastatin/therapeutic use , Pyrroles/therapeutic use , Simvastatin/therapeutic use , Treatment Outcome
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