72 +/- 1.84 %1D/g at 1
h) that was reduced by a blocking dose of unlabeled progestin R5020, but the nonspecific uptake in blood and muscle (2.11 +/- 0.14 and 0.89 +/- 0.16 % 1D/g at 1 h, respectively) was relatively high. [Br-76]16 alpha, 17 alpha-[(R)-1'-alpha-(5-bromofurylmethylidene)dioxyl]-21-hydroxy-19-norpregn-4-ene-3,20-dione 3 was stable in whole rate blood in vitro, but it was not stable in vivo due to the fast metabolism that occurred in the liver, resulting in the formation of a more polar radioactive metabolite and free [Br-76] bromode. The level of free[Br-76] bromide in blood remained high durign the experiment (2.11 +/- 0.14 and 0.89 +/- 0.16 % 1D/g at 1 h and 1.52 +/- 0.24 % 1D/g at 24 h). The tissue distribution of [Br-76]16 alpha, 17 alpha-[(R)-1'-alpha-(5-bromofurylmethylidene)dioxyl]-21-hydroxy-19-norpregn-4-ene-3,20-dione Cl-amidine 3 at 1 and 3 h was this website compared
with that of the F-18 analogs, [F-18]FFNP fluoro furanyl norprogesterone (FFNP) 1 and ketal 2.
Conclusion: [Br-76]16 alpha, 17 alpha-[(R)-1'-alpha-(5-bromofurylmethylidene)dioxyl]-21-hydroxy-19-norpregn-4-ene-3,20-dione 3 may have potential for imaging PR-positive breast tumors at carly time points, but it is not suitable for imaging at later times of for radiotherapy. (C) 2008 Elseiver Inc. All rights reserved.”
“Existing live-attenuated flavivirus vaccines (LAV) could be improved by reducing their potential to recombine with naturally circulating viruses in the field. Since the highly conserved cyclization sequences (CS) found in the termini of flavivirus genomes must be complementary to each other to support
genome replication, we set out to identify paired mutant CS that could support the efficient replication of LAV but would be unable to support replication in recombinant viruses harboring one BMS202 wild-type (WT) CS. By systematic evaluation of paired mutated CS encoded in West Nile virus (WNV) replicons, we identified variants having single and double mutations in the 5′- and 3′-CS components that could support genome replication at WT levels. Replicons containing only the double-mutated CS in the 5′ or the 3′ ends of the genome were incapable of replication, indicating that mutated CS could be useful for constructing safer LAV. Despite the identity of the central portion of the CS in all mosquito-borne flaviviruses, viruses carrying complementary the double mutations in both the 5′- and the 3′-CS were indistinguishable from WT WNV in their replication in insect and mammalian cell lines. In addition to the utility of our novel CS pair in constructing safer LAV, we demonstrated that introduction of these mutated CS into one component of a recently described two-component genome system (A. V. Shustov, P. W. Mason, and I. Frolov, J. Virol.
Combining analytical and bioanalytical methods, a good understanding of the reaction mechanisms, the enzymes catalysing them and the organization of
the genes encoding them could be gained. First studies on the use of Sphingomonas sp. strain TTNP3 in wastewater treatment have been performed revealing promising results.”
“This study examined clinical characteristics and laboratory-measured impulsive behavior of adolescents engaging in either non-suicidal self-injury with (NSSI + SA: n = 25) or without (NSSI-Only; n = 31) suicide attempts. We hypothesized that adolescent with NSSI + SI would exhibit PF-562271 more severe clinical symptoms and higher levels of behavioral impulsivity compared to adolescents with NSSI-Only. Adolescents were recruited from an inpatient psychiatric hospital unit and the two groups
were compared on demographic characteristics, psychopathology, self-reported clinical ratings, methods of non-suicidal self-injury, and two laboratory impulsivity measures. Primary evaluations were conducted during psychiatric hospitalization, and a subset of those tested during hospitalization was retested 4-6 weeks after discharge. During hospitalization, NSSI + SA patients reported worse depression, hopelessness, and impulsivity on standard clinical measures, and demonstrated elevated impulsivity SB431542 on a reward-directed laboratory measure compared to NSSI-Only patients. In the follow-up analyses, depression, hopelessness, suicidal ideation, and laboratory impulsivity were improved for both groups, but the NSSI+SA group still exhibited significantly more depressive symptoms,
hopelessness, and impulsivity than the NSSI-Only group. Risk assessments learn more for adolescents with NSSI + SA should include consideration not only of the severity of clinical symptoms but of the current level impulsivity as well. (C) 2008 Published by Elsevier Ireland Ltd.”
“Immobilizing enzymes can expand their applicability to continuous process operations and facilitates process intensification. An optimized formulation of immobilized biocatalysts is therefore of strategic interest in the field of industrial biotechnology. Nevertheless, biocatalyst formulation still largely relies on empirical approaches which lack effectiveness in the identification of optimum immobilization conditions.
In the present study, design of experiments, multiple linear regressions and modeling were used to screen, interpret and finally optimize crucial immobilization parameters. A laccase preparation from Coriolopsis polyzona MUCL38443 was immobilized via a sequential adsorption-crosslinking process on mesoporous silica particles. As a target variable, biocatalyst activity was doubled (similar to 280 U g(-1)) while dramatically reducing processing time (two hours instead of 26 hours) and reagent inputs (80 mM instead of 1 M glutaraldehyde (GLU)).
The effects of the IL18RAP and TAGAP alleles confer protection in type 1 diabetes and susceptibility in celiac disease. Loci with distinct effects in the two diseases included INS on chromosome 11p15, IL2RA on chromosome 10p15, and PTPN22 on chromosome 1p13 in type 1 diabetes and IL12A on 3q25 and LPP on 3q28 in celiac disease.
Conclusions: Torin 2 solubility dmso A genetic susceptibility to both type 1 diabetes and celiac disease shares common alleles. These data suggest that common biologic mechanisms, such as autoimmunity-related tissue damage and intolerance to dietary antigens, may be etiologic features of both diseases.”
“Some patients with proteinase
3 specific anti-neutrophil cytoplasmic autoantibodies (PR3-ANCA) also have antibodies that react to complementary-PR3 (cPR3), a protein encoded by the antisense RNA of
the PR3 gene. To study whether patients with anti-cPR3 antibodies have cPR3-responsive memory T cells we selected conditions selleck screening library that allowed cultivation of memory cells but not naive cells. About half of the patients were found to have CD4 + TH1 memory cells responsive to the cPR3(138-169)-peptide; while only a third of the patients had HI-PR3 protein responsive T cells. A significant number of T cells from patients responded to cPR3(138-169) peptide and to HI-PR3 protein by proliferation and/or secretion of IFN-gamma, compared to healthy controls while there was no response to scrambled peptide. Cells responsive to cPR3(138-169)-peptide were not detected in MPO-ANCA patients suggesting that this response is specific. The HLADRB1* 15 allele was significantly overrepresented in our patient group and is predicted to bind cPR3(138-169) peptide with high affinity. Regression analysis showed a significant likelihood that anti-cPR3 antibodies and PD-1/PD-L1 Inhibitor 3 clinical trial cPR3-specific T cells coexist in individuals, consistent with an immunological history of encounter with a PR3-complementary protein. We suggest
that the presence of cells reacting to potential complementary protein pairs might provide an alternative mechanism for auto-immune diseases.”
“Background: The myeloproliferative disorders are clonal disorders with frequent somatic gain-of-function alterations affecting tyrosine kinases. In these diseases, there is an increase in DNA damage and a risk of progression to acute leukemia. The molecular mechanisms in myeloproliferative disorders that prevent apoptosis induced by damaged DNA are obscure.
Methods: We searched for abnormalities of the proapoptotic Bcl-x(L) deamidation pathway in primary cells from patients with chronic myeloid leukemia (CML) or polycythemia vera, myeloproliferative disorders associated with the BCR-ABL fusion kinase and the Janus tyrosine kinase 2 (JAK2) V617F mutation, respectively.
This has allowed the calculation of the hemoglobin nitrite reductase activity rate profiles for the human hemoglobin and for bovine hemoglobin. The properties of these rate profiles are discussed. (C) 2013 Elsevier Inc. All rights reserved.”
“Meiosis is the cell division that generates haploid gametes from diploid precursors. To provide insight into the functional proteome of budding yeast during meiosis, a 2-D DIGE kinetic approach was used to study proteins in the pH 6-11
range. Nearly 600 protein spots were visualised 3-deazaneplanocin A and 79 spots exhibited statistically significant changes in abundance as cells progressed through meiosis. Expression changes of up to 41-fold were detected and protein sequence information was obtained for 48 spots. Single protein identifications https://www.selleckchem.com/products/lgk-974.html were obtained for 21 spots including different gel mobility forms of 5 proteins. A large number of post-translational events are suggested for these proteins, including processing,
modification and import. The data are incorporated into an online 2-DE map of meiotic proteins in budding yeast, which extends our initial DIGE investigation of proteins in the pH 4-7 range. Together, the analyses provide peptide sequence data for 84 protein spots, including 50 single-protein identifications and gel mobility isoforms of 8 proteins. The largest classes of identified proteins include carbon metabolism, protein catabolism, protein folding, protein synthesis and the oxidative stress response. A number of the corresponding genes are required for yeast
meiosis and recent studies have identified similar classes of proteins expressed during mammalian meiosis. This proteomic investigation and the resulting protein reference map make an important contribution towards a more detailed molecular view of yeast meiosis.”
“Preeclampsia (PE) is characterized by hypertension and proteinuria. It has been classified in early or late according to gestational age at the onset of disease. Endothelial dysfunction plays a crucial part in its pathogenesis. NO is a potent vasodilator and ADMA is its endogenous inhibitor. We have assessed maternal ADMA levels. Blasticidin S ADMA were increased in early [0.66 mu mol/L] versus late sPE [0.47 mu mol/L] (P = 0.001) and versus normotensive pregnant [0.48 mu mol/L] (P = 0.001). Our findings suggest that high ADMA levels in early sPE could compromise NO synthesis contributing to endothelial dysfunction, leading to impaired placentation and the onset of this disease. (C) 2013 Elsevier Inc. All rights reserved.”
“Systemic juvenile idiopathic arthritis (SJIA) is a chronic arthritis of children characterized by a combination of arthritis and systemic inflammation. There is usually non-specific laboratory evidence of inflammation at diagnosis but no diagnostic test.
To test this hypothesis, rats were subjected to intraseptal infusions of 8-OH-DPAT (or phosphate-buffered saline) during acquisition of a water maze task before and/or after 192 IgG-saporin-induced MS cholinergic lesion (vs. sham-operated).
We confirmed that only pre-acquisition intraseptal 8-OH-DPAT infusions prevented learning and subsequent drug-free retrieval of
the platform location in intact rats and found that (1) the cholinergic lesion did not prevent recall of the platform location, and (2) the impairing effects of 8-OH-DPAT were similar in sham-operated and lesioned rats, whether na < ve or not, to the task before lesion surgery.
An action of 8-OH-DPAT on only MS cholinergic neurons is not sufficient to account for the drug-induced memory impairments.
A concomitant 8-OH-DPAT-induced hyperpolarisation of cholinergic and/or GABAergic and/or glutamatergic Dactolisib solubility dmso neurons (intact rats), or of only GABAergic and/or glutamatergic ones after cholinergic lesion, might be necessary to obliterate task acquisition, confirming that, in the MS, (1) the three neuronal populations could cooperate to process hippocampal-dependent information, and (2) non-cholinergic septohippocampal neurons might be more important than cholinergic ones in serotonin-induced modulation of hippocampus-dependent memory processing.”
“Retroviruses integrate into cellular DNA nonrandomly. Lentiviruses such as human immunodeficiency virus type 1 (HIV-1) favor the bodies of active genes www.selleckchem.com/products/Liproxstatin-1.html and gene-enriched transcriptionally active regions of chromosomes. The interaction between lentiviral integrase and the cellular protein lens epithelium-derived growth factor (LEDGF)/p75 underlies the targeting of gene bodies, whereas recent research has highlighted roles for the HIV-1
capsid (CA) protein and cellular factors implicated in viral nuclear import, including transportin 3 (TNPO3) and nucleoporin 358 (NUP358), in the targeting of gene-dense regions of chromosomes. Here, we show that CA mutations, which include the substitution of Asp for Asn74 (N74D), significantly reduce the dependency of HIV-1 on LEDGF/p75 during infection and that this difference correlates with the efficiency of viral DNA integration. The of distribution of integration sites mapped by Illumina sequencing confirms that the N74D mutation reduces integration into gene-rich regions of chromosomes and gene bodies and reveals previously unrecognized roles for NUP153 (another HIV-1 cofactor implicated in viral nuclear import) and LEDGF/p75 in the targeting of the viral preintegration complex to gene-dense regions of chromatin. A role for the CA protein in determining the dependency of HIV-1 on LEDGF/p75 during infection highlights a connection between the viral capsid and chromosomal DNA integration.
Moreover, transfection with pCRE-Luc plasmid followed by immunoblotting demonstrated that NP activated CRE sites and CRE binding protein (CREB) phosphorylation. NP also increased nuclear CREB accumulation and CREB binding to the COX-2 promoter. Phosphatidylinositol 3 (PI3)-kinase, Akt, and the mitogen-activated protein kinases (MAP kinases) p38 and JNK were also significantly activated by NP. Our data demonstrate that NP induces COX-2 expression
through the PI3-kinase/Akt/MAP kinases/CRE pathway. These findings provide insight into the signal transduction pathways involved in the inflammatory responses induced by NP in macrophages.”
“The purpose of this study was to determine whether respiratory disturbance to posture varies as a function WH-4-023 research buy of the respiratory mode, i.e. thoracic or abdominal. To this aim, 10 healthy male subjects underwent a posturographic examination Palbociclib ic50 associated with a measurement of respiratory kinematics. Experimental conditions varied posture (sitting, standing) respiratory amplitude (quiet breathing, deep
breathing) and respiratory mode (thoracic, abdominal). In addition to classical posturographic parameters, original peak detection algorithm and emergence parameter calculated from the Fast Fourier Transform were used to assess the respiratory component in CP displacements. Results showed that along the antero-posterior axis, time domain and frequency domain parameters were both significantly greater in thoracic breathing mode than in abdominal mode. It was concluded that respiratory kinematics have a more prominent disturbing effect on posture when they involve the rib cage rather than the abdomen. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Ceramide induces cell cycle arrest and apoptotic cell death associated with increased levels of p27kip1. The aim of this study was to examine the effects of ceramide on p27kip1 protein levels as a measure of cell cycle arrest and apoptosis. Results showed that ceramide
increased p27kip1 protein levels through activation Galeterone of protein phosphatase 2A (PP2A) in PC-3 prostate cancer cells. Treatment of cells with the PP2A inhibitor okadaic acid or with PP2A-C siRNA inhibited ceramide-induced enhanced p27kip1 protein expression and Akt dephosphorylation, and prevented Skp2 downregulation. Overexpression of constitutively active Akt attenuated ceramide-induced Skp2 downregulation and p27kip1 upregulation. In addition, ceramide stimulated binding of the PP2A catalytic subunit PP2A-C to Akt as assessed by immunoprecipitation experiments, indicating that PP2A is involved in the induction of p27kip1 via inhibition of Akt pathway. Finally, whether PP2A can regulate p27kip1 expression independently of Akt pathway was determined. Knockdown of PP2A-C with siRNA reduced p27kip1 levels in the presence of Akt inhibitor.
Patients 1 and 4 received radiation and patient 3 underwent radical prostatectomy. Of the 2 patients who did not receive definitive treatment 1 was lost to followup (patient 2) and was treated conservatively by his family doctor. Patient 5 elected androgen deprivation therapy rather than radical treatment.
Conclusions: click here The low prostate cancer mortality in our surveillance cohort provides support for an active surveillance approach to favorable risk prostate cancer. Only 1 of the 5 patients presented with favorable
disease and experienced a theoretically preventable death. The absence of preventable deaths suggests that the basic approach is sound. Two patients had a trigger for intervention but did not receive it. This reinforces the importance of close monitoring and of definitive treatment for those in whom disease is reclassified as higher risk over time.”
“Purpose: Salvage radical prostatectomy is associated
with a higher complication rate than radical prostatectomy without prior radiotherapy but the magnitude of the increase is not well delineated.
Materials and Methods: A total of 3,458 consecutive patients underwent open radical prostatectomy and 98 underwent open salvage radical prostatectomy from January 1999 to June 2007. Data were collected from prospective surgical and institutional morbidity databases, and retrospectively from billing records and medical records. Medical
and surgical complications were captured, graded by the modified Clavien classification and classified by time of onset.
Results: Median followup PX-478 after salvage radical prostatectomy and radical prostatectomy was 34.5 and 45.5 months, respectively. Patients with salvage had significantly higher median age, modified Charlson comorbidity score, clinical and pathological stage, and Gleason score. They were less likely to have organ confined disease and more likely to have seminal vesicle invasion and nodal metastasis. There was no significant difference in median operative time, blood loss or transfusion rate. The salvage group had a higher adjusted probability of medical and surgical complications, including urinary tract infection, bladder neck contracture, urinary retention, urinary fistula, abscess and most rectal injury. Only 1 of 4 potent patients with salvage prostatectomy who underwent bilateral nerve sparing recovered erection adequate for intercourse. The 3-year actuarial recovery of continence was 30% (95% CI 19-41).
Conclusions: Medical and surgical complications of prostatectomy are significantly increased in the setting of prior radiotherapy. Understanding the magnitude of this increased risk is important for patient counseling.”
“Purpose: We evaluated predictors of freedom from biochemical recurrence in patients with pelvic lymph node metastasis at radical prostatectomy.
(c) 2008 Elsevier Inc. All rights reserved.”
“Broadly cross-reactive human immunodeficiency virus (HIV)-neutralizing antibodies are infrequently elicited in infected humans. The two best-characterized gp41-specific cross-reactive neutralizing human monoclonal antibodies, 4E10 and 2F5, target linear epitopes in the membrane-proximal external region (MPER) and bind to cardiolipin and several other autoantigens.
It has been hypothesized that, because of such reactivity to self-antigens, elicitation of 2F5 and 4E10 and similar antibodies by vaccine immunogens based on the MPER could be affected by tolerance mechanisms. Here, we report the identification and characterization of a novel anti-gp41 monoclonal antibody, designated m44, which neutralized Apoptosis inhibitor most of the 22 HIV type 1 (HIV-1) primary isolates from different clades tested in assays based on infection
of peripheral blood mononuclear cells by replication-competent virus but did not bind to cardiolipin and phosphatidylserine in an enzyme-linked immunosorbent assay and a Biacore assay nor to any protein or DNA autoantigens tested in Luminex assays. m44 bound to membrane-associated HIV-1 envelope glycoproteins (Envs), to recombinant Envs lacking the transmembrane domain and cytoplasmic tail (gp140s), and to gp41 structures containing five-helix bundles and six-helix bundles, but not to N-heptad repeat trimers, suggesting that the C-heptad repeat is involved in m44 binding. In contrast to 2F5, 4E10, and Z13, m44 did not bind to any significant degree Pitavastatin to denatured gp140 and linear peptides derived from gp41, suggesting a conformational nature of the epitope. This is the first report of a gp41-specific cross-reactive HIV-1-neutralizing human antibody that does not have detectable reactivity Celastrol to autoantigens. Its novel conserved conformational epitope on gp41 could be helpful in the design of vaccine immunogens and as a target for therapeutics.”
“To investigate the possible
involvement of the nitric oxide radical (NO) in ciguatera fish poisoning (CFP), the in vitro effects of the main Pacific ciguatoxin (P-CTX-1B) and bacterial lipopolysaccharide (LPS) were comparatively studied on neuroblastoma Neuro-2a and on macrophage RAW 264.7 cell lines. NO accumulation was quantified by measuring nitrite levels in cellular supernatant using Griess reagent while the up-regulation of inducible nitric oxide synthase (iNOS) at the mRNA level was quantified via Real-Time Reverse-Transcription Polymerase Chain Reaction (RT-PCR). P-CTX-1B caused a concentration-and time-dependent induction of iNOS in RAW 264.7 cells but not in Neuro-2a cells. NO production was evidenced by increased nitrite levels in the 10 mu M range after 48 h of RAW 264.7 cells exposure to LPS and P-CTX-1B (0.05 mu g/ml and 6 nM, respectively). The expression of MOS mRNA peaked at 8 h for LPS then gradually decreased to low level at 48 h. In contrast, a sustained level was recorded with P-CTX-1B in the 8-48 h time interval.
Methods: 223 schizophrenia patients were tested with Wisconsin Card Sorting Test (WCST), for the evaluation of cognitive flexibility, Continuous Performance Test (CPT), for see more the evaluation of attention, and genotyped for the 5-HTTLPR.
Results: We found a significant association between HTT polymorphism and executive functions and inversely with sustained attention. The presence of the high-activity long (L) allele in homozygosis was a predictor of better executive performances and poorer performances of attention.
Conclusions: Our findings suggest that factors affecting serotonin availability may play a specific role in cognitive processes, probably through complex modulation of the different
performance components. (C) 2009 Elsevier Inc. All rights reserved.”
“While RNA silencing is a potent antiviral defense in plants, well-adapted plant viruses are known to encode suppressors of RNA silencing (VSR) that can neutralize the effectiveness of RNA silencing. As a result, most plant genes involved in antiviral silencing were identified by using debilitated viruses lacking silencing suppression capabilities. Therefore, it remains to be resolved whether RNA silencing plays a significant part in defending plants against wild-type viruses. We report here that, at a higher Belinostat plant growth temperature
(26 C) that permits rigorous replication of Turnip crinkle Quisqualic acid virus (TCV) in Arabidopsis, plants containing loss-of-function mutations within the Dicer-like 2 (DCL2), Argonaute 2 (AGO2), and HEN1 RNA methyltransferase genes
died of TCV infection, whereas the wild-type Col-0 plants survived to produce viable seeds. To account for the critical role of DCL2 in ensuring the survival of wild-type plants, we established that higher temperature upregulates the activity of DCL2 to produce viral 22-nucleotide (nt) small interfering RNAs (vsRNAs). We further demonstrated that DCL2-produced 22-nt vsRNAs were fully capable of silencing target genes, but that this activity was suppressed by the TCV VSR. Finally, we provide additional evidence supporting the notion that TCV VSR suppresses RNA silencing through directly interacting with AGO2. Together, these results have revealed a specialized RNA silencing pathway involving DCL2, AGO2, and HEN1 that provides the host plants with a competitive edge against adapted viruses under environmental conditions that facilitates robust virus reproduction.”
“Opportunistic bacterial infections of the nasal cavity could potentially lead to infection of the brain if the olfactory or trigeminal nerves are colonised. The olfactory nerve may be a more susceptible route because primary olfactory neurons are in direct contact with the external environment. Peripheral glia are known to be able to phagocytose some species of bacteria and may therefore provide a defence mechanism against bacterial infection.
Although both groups had reductions in craving and anxiety with smoking, the regular cigarette group had a greater improvement in mood. For the total group, change in BP correlated inversely with change in mood, indicating that
greater smoking-induced DA release was associated with more LB-100 clinical trial smoking-related mood improvement. Thus, nicotine delivered through cigarette smoking appears to be important for ventral striatal DA release. Study findings also suggest that mood improvement from smoking is specifically related to ventral striatal DA release.”
“Objective: This study evaluated trends in hospitalizations, treatment, and mortality of ruptured abdominal aortic aneurysms (rAAAs) in the United States Medicare population.
Methods: The Medicare inpatient database (1995 through 2006) was reviewed for patients with rAAA and AAA by using International Classification of Disease (9th Clinical Modification) codes for rAAA and AAA. Proportions and trends were analyzed by chi(2) analysis, continuous variables by t test, and trends by the Cochran-Armitage test.
During the study period, LY2874455 mw hospitalizations with the diagnoses of rAAA declined from 23.2 to 12.8 per 100,000 Medicare beneficiaries (P < .0001), as did repairs of rAAA (15.6 to 8.4 per 100,000; P < .0001). No change was observed in AAA elective repairs. The 30-day
mortality rate after open repair of rAAA decreased by 4.9% (from 39.6% to 34.7%; Elesclomol (STA-4783) P = .0007 for trend) for the age group 65 to 74 and by 2.4% (from 52.9% to 50.5%, P = .0008) for the age group >= 75. Perioperative mortality after endovascular repair diminished by 13.6% (from 43.5% in 2001 to 29.9% in 2006; P = .0020). Mortality among women was higher than among men (51.1% vs 40.0% in 2006). The demographics of patients treated for rAAA changed to include a greater proportion of women and patients aged 75 years.
Conclusion: A significant decrease has Occurred in the number of patients who have a diagnosis of rAAA and undergo treatment, but there has been no change in repairs of AAA. The perioperative mortality rate has improved due to the introduction of endovascular repair and a small but progressive improvement in survival after open repair for patients aged 65 to 74 years. (J Vase Surg 2008;48:1101-7.)”
“Initial effects of drugs of abuse seem to converge on the mesolimbic dopamine pathway originating from the ventral tegmental area (VTA). Even after a single dose, many drugs of abuse are able to modulate the glutamatergic transmission activating the VTA dopamine neurons, which may represent a critical early stage in the development of addiction.