Drinks industry response.
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Alcohol Drinking↗
Biomedical subjects
B Alexander
Publications and source records attributed to B Alexander.
Sampling methods for phlebotomine sandflies.
A review is presented of methods for sampling phlebotomine sandflies (Diptera: Psychodidae). Among approximately 500 species of Phlebotominae so far described, mostly in the New World genus Lutzomyia and the Old World genus Phlebotomus, about 10% are known vectors of Leishmania parasites or other pathogens. Despite being small and fragile, sandflies have a wide geographical range with species occupying a considerable diversity of ecotopes and habitats, from deserts to humid forests, so that suitable methods for collecting them are influenced by environmental conditions where they are sought. Because immature phlebotomines occupy obscure terrestrial habitats, it is difficult to find their breeding sites. Therefore, most trapping methods and sampling procedures focus on sandfly adults, whether resting or active. The diurnal resting sites of adult sandflies include tree holes, buttress roots, rock crevices, houses, animal shelters and burrows, from which they may be aspirated directly or trapped after being disturbed. Sandflies can be collected during their periods of activity by interception traps, or by using attractants such as bait animals, CO2 or light. The method of trapping used should: (a) be suited to the habitat and area to be surveyed, (b) take into account the segment of the sandfly population to be sampled (species, sex and reproduction condition) and (c) yield specimens of appropriate condition for the study objectives (e.g. identification of species present, population genetics or vector implication). Methods for preservation and transportation of sandflies to the laboratory also depend on the objectives of a particular study and are described accordingly.
Animals↗
H(2)O(2)-mediated permeability: role of MAPK and occludin.
H(2)O(2)-mediated elevation in endothelial solute permeability is associated with pathological events such as ischemia-reperfusion and inflammation. To understand how H(2)O(2) mediates increased permeability, we investigated the effects of H(2)O(2) administration on vascular endothelial barrier properties and tight junction organization and function. We report that H(2)O(2) exposure caused an increase in endothelial solute permeability in a time-dependent manner through extracellularly regulated kinase 1 and 2 (ERK1/ERK2) signal pathways. H(2)O(2) exposure caused the tight junctional protein occludin to be rearranged from endothelial cell-cell junctions. Occludin rearrangement involved redistribution of occludin on the cell surface and dissociation of occludin from ZO-1. Occludin also was heavily phosphorylated on serine residues upon H(2)O(2) administration. H(2)O(2) mediates changes in ERK1/ERK2 phosphorylation, increases endothelial solute permeability, and alters occludin localization and phosphorylation were all blocked by PD-98059, a specific mitogen-activated protein (MAP) or ERK kinase 1 inhibitor. These data strongly suggest that H(2)O(2)-mediated increased endothelial solute permeability involves the loss of endothelial tight junction integrity through increased ERK1/ERK2 activation.
Cell Membrane↗
The London Depression Intervention Trial. Randomised controlled trial of antidepressants v. couple therapy in the treatment and maintenance of people with depression living with a partner: clinical outcome and costs.
BACKGROUND: Relapse of depression is associated with a criticising attitude of the patient's partner. AIMS: To compare the relative efficacy and cost of couple therapy and antidepressant drugs for the treatment and maintenance of people with depression living with a critical partner. METHOD: A randomised controlled trial of antidepressant drugs v. couple therapy. The subjects were 77 people meeting criteria for depression living with a critical partner. RESULTS: Drop-outs were 56.8% [corrected] from drug treatment and 15% from couple therapy. Subjects' depression improved in both groups, but couple therapy showed a significant advantage, according to the Beck Depression Inventory, both at the end of treatment and after a second year off treatment. Adding the costs of the interventions to the costs of services used showed there was no appreciable difference between the two treatments. CONCLUSIONS: For this group couple therapy is much more acceptable than antidepressant drugs and is at least as efficacious, if not more so, both in the treatment and maintenance phases. It is no more expensive overall.
Adult↗
Characterization of JOK-1, a human gastric epithelial cell line.
Human gastric epithelial cells were isolated from samples of human gastric lining and immortalized with simian virus 40 (SV40) to generate the stable human gastric epithelial cell line "JOK-l." These cells express conventional epithelial markers (vimentin, cytokeratin-18, occludin, N- and E-cadherins, beta-catenin, ZO-1, ZO-2, mucin, epithelial specific antigen) as well as SV40 large T-antigen. These cells rapidly externalized E-cadherin in response to acidic medium, and exhibited epithelial-like barrier properties that are also regulated by media pH. In contrast, the kidney epithelial cell line "MDCK" also expresses several epithelial markers (vimentin, cytokeratin-18, occludin, N- and E-cadherin, beta-catenin, ZO-1, ZO-2, epithelial specific antigen), but does not express mucin, or large T-antigen. However, MDCK rapidly internalize their E-cadherin from the cell surface and increase the solute flux in an acidic medium. These data suggest that the JOK-1 cell line is a potentially useful cell line for developing models of gastric epithelial function, development, and disease.
Antigens, Polyomavirus Transforming↗
Increased rate of trazodone prescribing with bupropion and selective serotonin-reuptake inhibitors versus tricyclic antidepressants.
OBJECTIVE: To determine whether trazodone is prescribed significantly more often with selective serotonin-reuptake inhibitors (SSRIs) and bupropion than with tricyclic antidepressants (TCAs). METHODS: A retrospective analysis of Iowa City Department of Veteran's Affairs prescription records from March 1, 1995, to March 1, 1998, was performed. Antidepressants prescribed only by psychiatrists were included. Concomitant use was defined as trazodone prescribed on the same date or up to 42 days after the fill date of the primary antidepressant. STATISTICS: All comparisons used 2 x 2 chi 2 contingency table. Significance level was set at p < 0.05. RESULTS: Significantly more patients were prescribed trazodone concurrently with bupropion and SSRI antidepressants than with TCAs. Trazodone was prescribed significantly more often for patients receiving an SSRI (p = 0.0001, chi 2 = 14.59) or bupropion (p = 0.0295, chi 2 = 4.74) than for patients receiving a TCA. There was no significant difference in trazodone use between the patients taking SSRIs or bupropion. The percent of patients that received an SSRI, bupropion, or a TCA in combination with trazodone was 27%, 23%, and 13%, respectively. Overall, 23.7% of patients received trazodone concomitantly with a primary antidepressant. DISCUSSION: The effects of antidepressants on sleep and on sleep scores of depression rating scales are reviewed. The clinical implications of these findings are discussed. The literature addressing the effects of antidepressants on sleep and on sleep scores of depression rating scales is summarized. Although sleep studies suggest that SSRIs may not improve sleep as well as a TCA, clinical studies do not often support these findings. Several studies report that bupropion may not improve sleep parameters as well as doxepin or trazodone. The clinical implications of these findings are discussed. CONCLUSIONS: We have demonstrated that our clinicians prescribe trazodone at a significantly higher rate with an SSRI or bupropion than with a TCA. The exact reason for this difference is not known. If trazodone is used during the first six weeks of an initial antidepressant treatment trial, it should be discontinued to determine whether the patient's sleep disturbance has responded to the primary antidepressant. More comparison studies among the newer antidepressants and between classes of antidepressants concerning their effects on sleep in the depressed patient need to be performed.
Antidepressive Agents, Tricyclic↗
Diabetes mellitus associated with clozapine therapy.
Clozapine is an atypical antipsychotic that is associated with certain adverse effects that limit its usefulness. Published case reports have associated clozapine with impairment of glucose tolerance, including the onset or exacerbation of diabetes mellitus. We report two patients who experienced diabetes mellitus associated with the agent.
Antipsychotic Agents↗
Rapid, high-yield method for the bulk purification of fibronectin from human plasma.
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Adult↗
Increased risk of side-effects in psychiatric patients treated with clozapine and carbamazepine: a reanalysis.
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Agranulocytosis↗
Mycoses in the transplanted patient.
The incidence of invasive fungal infection (IFI) has increased considerably over the past 20 years, and transplant recipients are at especially high risk for fungal infections owing to their overall immunosuppressed condition. Organ transplantation procedures were incorporated as a therapeutic option for many patients who lacked the normal functions of organs such as the heart, liver, kidney, lung, pancreas and small bowel. The prevalence of IFI in solid organ transplant (SOTR) patients ranges from 5 to 50% in kidney and liver transplants, respectively. In bone marrow transplant (BMT) patients, IFI are major causes of morbidity and mortality due to the protracted neutropenic period and graft-versus-host disease. Candida spp. and Aspergillus spp. account for >80% of fungal episodes in both SOTR and BMT. The development of new immunosuppressive agents, new prophylaxis strategies (as pre-emptive therapy) and the improvement in surgical techniques led to increase survival of transplant recipients. In this session, a clear and concise update of the recent advances in the laboratory diagnosis of candidiasis and aspergillosis in this kind of patients was presented. However, we still need to establish more rapid, sensitive and specific methods for IFI diagnosis. Representatives of the 'Subcomision de Infecciones en el Paciente Neutropenico y Transplantado (SIPNYT)' de la Sociedad Argentina de Infectologia (SADI), presented the results of an unusual multicenter study both retrospective and descriptive studies of IFI in SOTR and BMT patients in Argentina. In addition, a study of IFI in 1,861 SOTR patients from four centers and the analysis of IFI in 2,066 BMT patients from all 12 BMT centers from Argentina was presented. From these studies it can be concluded that 'all transplant recipients are not the same' and that they should be stratified according to their different risk degrees in order to determine the best prophylaxis and treatment strategies.
Bone Marrow Transplantation↗
Hypoxia attenuates hepatic arterial vasodilatation and enhances portal venous vasoconstriction to ATP in the perfused rabbit liver.
Dose-related responses to acetylcholine, adenosine 5'-triphosphate (ATP), adenosine and sodium nitroprusside were studied in an in vitro perfused rabbit liver gassed with (95% N(2)/5% CO(2), Group 1) and without carbon dioxide (100% N(2), Group 2). At raised tone, achieved by addition of methoxamine to the perfusate, significantly attenuated hepatic arterial vasodilatation to sodium nitroprusside, acetylcholine, ATP and adenosine was measured in Group 1 and responses to all but sodium nitroprusside were abolished in Group 2. Portal venous responses to acetylcholine, adenosine and sodium nitroprusside were not significantly altered in either Group 1 or Group 2. However, portal venous vasoconstriction to ATP was significantly enhanced in Group 1 and less so in Group 2. It is concluded that carbon dioxide-free hypoxia attenuated hepatic arterial vasodilatation to acetylcholine and ATP and enhanced vasoconstriction to ATP. Both these effects may be characteristic of damage to the microvascular endothelium and may be the result of decreased synthesis of nitric oxide.
Acetylcholine↗
Localisation of hepatic vascular resistance sites in the isolated dual-perfused rat liver.
The locations of the vascular resistance sites which regulate vascular tone in the hepatic arterial and portal venous vasculatures of the rat liver were identified using a new, in vitro, dual-perfused liver preparation. Twelve livers of male Wistar rats were perfused via the hepatic artery and portal vein at fixed flow and at physiological pressure. Dose-related vasoconstriction to injections or infusions of noradrenaline was measured as transient or sustained increases in perfusion pressure, respectively, in the hepatic arterial and portal venous vasculatures. Direct injections/infusions of noradrenaline refer to those administered into the vasculature from which pressure was recorded, e.g., the effects of hepatic arterial (direct) injections/infusions of noradrenaline upon hepatic arterial perfusion pressure. Indirect injections/infusions of noradrenaline were those administered to the adjacent afferent vasculature, e.g., the effects of portal venous (indirect) injections of noradrenaline upon hepatic arterial perfusion pressure. The converse applies for recordings of portal venous perfusion pressure. The -log(M) ED50 values to direct (hepatic arterial) and indirect (portal venous) injections in the hepatic artery were 4.25+/-0.20 and 3.40+/-0.10, respectively, and were significantly different (P < 0.01, Student's unpaired t-test); the -log(M) ED50 values to direct (portal venous) and indirect (hepatic arterial) injections in the portal vein were 3.91+/-0.08 and 3.85+/-0.11, respectively, and were not significantly different (P > 0.05, Student's unpaired t-test). Similarly, the -log(M) ED50 values to direct (hepatic arterial) and indirect (portal venous) infusions in the hepatic artery were 5.28+/-0.11 and 3.75+/-0.12, respectively, and were significantly different (P < 0.01, Student's unpaired t-test); the -log(M) ED50 values to direct (portal venous) and indirect (hepatic arterial) infusions in the portal vein were 5.31+/-0.19 and 5.70+/-0.16, respectively, and were not significantly different (P > 0.05, Student's unpaired t-test). These results demonstrated that there is little transfer of noradrenaline from the portal venous to the hepatic arterial resistance sites, but significant transfer from the hepatic artery to the portal venous suggesting that; (a) the portal venous resistance sites are located at the sinusoidal or post-sinusoidal level; and (b) the hepatic arterial resistance sites are located at the pre-sinusoidal level.
Animals↗
An investigation of the relationship between the liver and brain using an isolated perfused rat brain preparation.
The pathogenesis of portal-systemic encephalopathy (PSE) and hepatic encephalopathy (HE), disorders of the brain attributed to abnormal liver function, are poorly understood. This study was conducted to examine if a fundamental, and possibly exclusive, homeostatic interrelationship exists between the liver and brain that might deteriorate during liver failure to result in the syndrome of PSE and HE. An isolated organ perfusion circuit was devised to accommodate an isolated rat brain and an isolated rat liver preparation perfused concomitantly. The survival time of the brain preparation was measured by the maintenance of the spontaneous electroencephalocorticogram and was extended from a median survival time of 35 min (range 22 to 53 min), when perfused alone, to 210 min (range 172 to 480 min), when perfused simultaneously with a liver. Also, concomitant perfusion with an isolated rat liver reduced perfusate glucose concentrations from 200 mg% to a range between 45 to 60 mg%. These data support our hypothesis that a homeostatic interrelationship exists between the liver and brain that is independent of other metabolic influences; disturbance of this relationship may contribute towards the syndrome of PSE and HE.
Animals↗
Paradoxical cholinergic and purinergic vascular reactivity of rabbit thoracic aorta cold-stored in University of Wisconsin solution.
Endothelial dysfunction has been reported in donor blood vessels destined for organ transplantation following cold-storage preservation with University of Wisconsin solution (UW). This was investigated in the present work. Segments of rabbit thoracic aorta were mounted on isometric fine-wire myographs at 37 degrees C and gassed with 95% O2/5% CO2. Concentration-dependent vasodilatations to acetylcholine and adenosine-5'-triphosphate (ATP) were obtained in freshly-harvested rabbit aortic rings, with and without the endothelium, and after 8 days of cold-storage, at 4 degrees C, in either UW, Krebs-Bülbring buffer (KBB) or saline. The action of the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (100 microM) was evaluated upon the concentration-response curves to determine whether nitric oxide (NO) exerted any modulatory actions. Endothelium-dependent, NO-mediated responses to acetylcholine were unaltered after eight days of storage in UW, reduced after storage in KBB and absent after removal of the vascular endothelium, saline storage or after testing in the presence of L-NAME, suggesting improved NO-mediated endothelial function with the use of UW. Structural preservation was also confirmed using scanning electron microscopy. In contrast, endothelium-dependent responses to ATP were unchanged after eight days of storage in KBB but were reduced after storage in UW and saline, suggesting purinergic (ATP) endothelial dysfunction after storage in UW. L-NAME markedly reduced vasodilatation to ATP in freshly harvested rings and after eight days of storage in KBB. This reduction was statistically significant (P < 0.05, Student's two tailed, unpaired t-test) at -log (M) ATP concentrations of 5.5, 5.0, 4.5, 4.0 and 3.5. NO-dependent vasodilatation to ATP was not attenuated by L-NAME in UW-stored rings. Eight days' UW-storage of rabbit thoracic aortic rings appeared to have differential and paradoxical effects upon NO-dependent vasodilatation to acetylcholine and ATP. Morphological observations using electron microscopy suggested that UW preserved the vascular endothelium and this was verified by retained vascular reactivity of endothelium-dependent vasodilatations to acetylcholine. UW-storage however, significantly reduced endothelium-dependent relaxation to ATP thereby suggesting that P2Y-purinoceptors, which are located on the vascular endothelium, may be more susceptible to biodegradation than cholinergic receptors and may be responsible for endothelial dysfunction following transplantation.
Acetylcholine↗
An investigation of shame and guilt in a depressed sample.
A self-report measure of proneness to shame and guilt was administered to 86 patients with moderate to severe depression, with the prediction that there would be a positive correlation of shame with severity of depression. Contrary to other, non-clinical studies, we found that guilt but not shame was associated with levels of depression. Shame-proneness demonstrated a unique association with a stable attributional style for negative outcomes, global negative self-evaluation, submissive behaviour and internalized anger. Contrary to prediction, no relationship was found between shame- or guilt-proneness and a reported history of childhood sexual abuse.
Adult↗
Breeding structure of the sand fly Lutzomyia longipalpis (Lutz & Neiva) in Brazil.
Eleven populations of Lutzomyia longipalpis (Lutz & Neiva), the sand fly vector of Leishmania chagasi, from different areas of Brazil were analyzed for genetic variation at 16 enzyme loci. In this region, the prevalence of visceral leishmaniasis (VL) caused by L. chagasi is spotty and reproductive isolation among populations of Lu. longipalpis has been reported. It is thought that morphologically similar cryptic species with varying vectorial capacity may be responsible for the discontinuous distribution of VL. The aim was to study the genetic structure of populations within this region and to identify demes that may represent sibling species. Genotypic frequencies within populations were in close compliance to Hardy-Weinberg expectations, suggesting there are no sympatric species among these 11 populations. Levels of genetic distance between pairs of populations were very low (< 0.03), consistent with local populations within a single sand fly species. When genotypic frequency data for all populations were pooled, 9 of the 13 polymorphic loci deviated from Hardy-Weinberg expectations, indicating some degree of genetic substructuring. Estimates of effective migration rates (N(e)m) among all populations were low, 2.73, suggesting that gene flow is restricted among populations, which is probably the reason for the observed genetic substructuring.
Alleles↗
IL-2 adenovector-transduced autologous tumor cells induce antitumor immune responses in patients with neuroblastoma.
In many different murine models, the immunogenicity of tumor cells can be increased by transduction with a range of immunostimulatory genes, inducing an immune response that causes regression of pre-existing unmodified tumor cells. To investigate the relevance of these animal models to pediatric malignancy, we used autologous unirradiated tumor cells transduced with an adenovirus-IL-2 to immunize 10 children with advanced neuroblastoma. In a dose-escalation study, we found that this tumor immunogen induced a moderate local inflammatory response consisting predominantly of CD4(+) T lymphocytes, and a systemic response, with a rise in circulating CD25(+) and DR+ CD3(+) T cells. Patients also made a specific antitumor response, manifest by an IgG antitumor antibody and increased cytotoxic T-cell killing of autologous tumor cells. Clinically, five patients had tumor responses after the tumor immunogen alone (one complete tumor response, one partial response, and three with stable disease). Four of these five patients were shown to have coexisting antitumor cytotoxic activity, as opposed to only one of the patients with nonresponsive disease. These results show a promising correlation between preclinical observations and clinical outcome in this disease, and support further exploration of the approach for malignant diseases of children.
Adenoviridae↗
Interleukin-2 gene-modified allogeneic tumor cells for treatment of relapsed neuroblastoma.
Tumor cells that have been genetically modified to express immunostimulatory genes will induce effective antitumor responses in a range of syngeneic animal models. For human applications, transduced autologous tumor cell lines are often difficult or impossible to prepare, so that there are strong incentives for substituting a standardized allogeneic tumor cell line. However, such lines may be inferior immunogens if they differ from host tumors in the antigens they express. We have evaluated the safety, immunostimulatory, and antitumor activity of an interleukin-2-secreting allogeneic neuroblastoma cell line in 12 children with relapsed stage IV neuroblastoma. They received two to four subcutaneous injections of cells in a dose-escalating schedule, up to a maximum of 10(8) cells per injection. There was induration and pruritus at the injection site, and skin biopsies revealed mild panniculitis with CD3+ cells surrounding scanty residual tumor cells. There was a limited but significant peripheral monocytosis. No patient showed any increase in direct cytotoxic effector function against the immunizing cell line, but 3 patients had a rise in the frequency of neuroblastoma-reactive cytotoxic T lymphocyte precursor cells. One child had > 90% tumor response (PR), 7 had stable disease, and 4 had progressive disease in response to vaccine alone. Although these results offer some encouragement for the continued pursuit of allogeneic vaccine strategies in human cancer, the antitumor immune responses we observed are inferior to those obtained in an earlier immunization study using autologous neuroblastoma cells. Hence, we suggest that this earlier approach remains preferable, its difficulties notwithstanding.
Cancer Vaccines↗