Biomedical subjects

M Russell

Publications and source records attributed to M Russell.

At least 37 records · Page 2Linked to original sources

PubMed1999

Comparability of nutrient estimation by three food frequency questionnaires for use in epidemiological studies.

Replication of results is an important issue in studies of diet and disease, possibly dependent on data collection method. We compared assessments from the Health Habits and History Questionnaire (HHHQ), the Harvard Semiquantitative Food Frequency Questionnaire (HFFQ), and the New York State Cohort Food Frequency Questionnaire (CFFQ) for estimates of daily intakes of energy, protein, carbohydrates, total fat, dietary fiber, cholesterol, vitamins A, C, and E, and carotenoids. Fifty-nine men and 50 women aged 35-73 years completed the HHHQ and HFFQ as interviews and the 44-food CFFQ as a self-administered mailed questionnaire. Comparability was assessed with Spearman correlation coefficients. Quantitation of nutrient intake differed by nutrient, questionnaire, and nutrient calculation method. Ranking on energy and macronutrient intake for the HHHQ and HFFQ ranged from 0.62 to 0.80; ranking for micronutrient intake ranged from 0.56 to 0.80. For the CFFQ with the HHHQ or HFFQ, correlations ranged between 0.29 and 0.62. The CFFQ performs comparably to the HHHQ and HFFQ for some, but not all, nutrients; our results suggest that the HHHQ and HFFQ can be used interchangeably with reasonable confidence in studies of diet and disease.

Adult↗

PubMed1999

A longitudinal study of stress, alcohol, and blood pressure in community-based samples of blacks and non-blacks.

Both alcohol use and stress appear to increase blood pressure. In addition, stress is associated with increased alcohol use. To investigate these relationships, researchers interviewed representative samples of the black and non-black adult household populations in Erie County, New York, in 1986, 1989, and 1993. The results support a causal relationship between stress and alcohol use and point to a number of factors that influence this relationship. Significant relationships between changes in alcohol use and blood pressure were also found. Although the researchers found little evidence for a direct effect of stress on blood pressure, stress related to family life, anxiety, and depression was associated with an increased risk for hypertension.

Adult↗

PubMed1998

Suicide by cop.

STUDY OBJECTIVE: "Suicide by cop" is a term used by law enforcement officers to describe an incident in which a suicidal individual intentionally engages in life-threatening and criminal behavior with a lethal weapon or what appears to be a lethal weapon toward law enforcement officers or civilians to specifically provoke officers to shoot the suicidal individual in self-defense or to protect civilians. The objective of this study was to investigate the phenomenon that some individuals attempt or commit suicide by intentionally provoking law enforcement officers to shoot them. METHODS: We reviewed all files of officer-involved shootings investigated by the Los Angeles County Sheriff's Department from 1987 to 1997. Cases met the following criteria: (1) evidence of the individual's suicidal intent, (2) evidence they specifically wanted officers to shoot them, (3) evidence they possessed a lethal weapon or what appeared to be a lethal weapon, and (4) evidence they intentionally escalated the encounter and provoked officers to shoot them. RESULTS: Suicide by cop accounted for 11% (n=46) of all officer-involved shootings and 13% of all officer-involved justifiable homicides. Ages of suicidal individuals ranged from 18 to 54 years; 98% were male. Forty-eight percent of weapons possessed by suicidal individuals were firearms, 17% replica firearms. The median time from arrival of officers at the scene to the time of the shooting was 15 minutes with 70% of shootings occurring within 30 minutes of arrival of officers. Thirty-nine percent of cases involved domestic violence. Fifty-four percent of suicidal individuals sustained fatal gunshot wounds. All deaths were classified by the coroner as homicides, as opposed to suicides. CONCLUSION: Suicide by cop is an actual form of suicide. The most appropriate term for this phenomenon is law enforcement-forced-assisted suicide. Law enforcement agencies may be able to develop strategies for early recognition and handling of law enforcement-forced-assisted suicide (suicide by cop). Health care providers involved in the evaluation of potentially suicidal individuals and in the resuscitation of officer-involved shootings should be aware of law enforcement-forced-assisted suicide as a form of suicide.

Adolescent↗

PubMed1998

Safety and immunogenicity of a combined five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus B conjugate vaccine administered to infants at two, four and six months of age.

Safety, immunogenicity and lot consistency of five-component pertussis combination vaccine (CPDT-IPV//PRP-T) in infants were compared to that of whole cell pertussis combination vaccine (DPT-IPV//PRP-T), as were separate and combined injections of CPDT-IPV and PRP-T. No significant differences in adverse event rates were observed between lots of CPDT-IPV//PRP-T or between separate or combined injections of CPDT-IPV and PRP-T. Minor differences in antibody responses were observed between lots of component pertussis vaccine. Higher concentrations of diphtheria and tetanus antitoxins were induced by separate than by combined injection of CPDT-IPV and PRP-T, but no other differences in immunogenicity were observed. Adverse reactions were more than twice as frequent after whole cell than after component pertussis vaccines. Antibody responses to pertussis toxoid, filamentous hemagglutin and pertactin were significantly greater after component vaccines, while the response to type 3 poliovirus was higher after whole cell vaccine. No significant differences were observed for other vaccine components. CPDT-IPV//PRP-T was safe and immunogenic in infants. Antibody results were similar to those observed in a Swedish field trial that demonstrated CPDT to be 85% effective in preventing clinical pertussis.

Acetaminophen↗

PubMed1998

A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party.

Transitional cell carcinomas may arise at any site within the urinary tract and are a source of considerable morbidity and mortality. In particular, patients with metastatic disease have a poor prognosis, with less than 5% alive at 5 years. A multicentre randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced or metastatic transitional cell carcinoma was conducted in the UK. From April 1991 to June 1995, 214 patients were entered by 16 centres, 108 randomized to CMV and 106 to MV. A total of 204 patients have died. The hazard ratio (relative risk of dying) was 0.68 (95% CI 0.51-0.90, P-value = 0.0065) in favour of CMV. This translates to an absolute improvement in 1-year survival of 13%, 16% in MV and 29% in CMV. The median survival for CMV and MV was 7 months and 4.5 months respectively. Two hundred and eight patients objectively progressed or died. The hazard ratio was 0.55 (95% CI 0.41-0.73, P-value = 0.0001) in favour of CMV. Two hundred and nine patients symptomatically progressed or died. The hazard ratio was 0.48 (95% CI 0.36-0.64, P-value = 0.0001) in favour of CMV. The most important pretreatment factors influencing overall survival were WHO performance status and extent of disease. These two factors were used to derive a prognostic index which could be used to categorize patients into three prognostic groups. We conclude that the addition of cisplatin to methotrexate and vinblastine should be considered in patients with transitional cell carcinoma, taking into account the increased toxicity.

Aged↗

PubMed1998

Evaluation of the provision of fieldwork training through a rural student unit.

A Rural Student Unit was established as a pilot project to trial a model of rural fieldwork placement provision. The Unit aimed to increase the number of student placements available in rural areas and provide undergraduate students with a positive fieldwork experience. The results indicate that the Unit was successful in overcoming some of the barriers to rural fieldwork, for both students and supervisors, and substantially increased the number of students undertaking fieldwork in this area. The results support the further trialing and expansion of the model.

Attitude of Health Personnel↗

PubMed1998

Molecular cloning and characterization of the genes coding for the highly immunogenic cluster of 90-kilodalton envelope proteins from the Chlamydia psittaci subtype that causes abortion in sheep.

Proteins present in the outer membrane of chlamydiae that are involved in mucosal epithelial cell infection must clearly be identified and characterized if we are to understand and modify the pathogenic mechanisms utilized by these organisms. We have identified and isolated a family of four genes encoding putative outer membrane proteins (POMPs), a group of proteins of approximately 90 kDa present in the outer membrane of the subtype of Chlamydia psittaci that causes ovine enzootic abortion (strain S26/3). These proteins, although minor components, are major immunogens, as shown by the immunoblotting of chlamydial outer membrane complexes with postabortion sheep sera, and are therefore potential diagnostic and/or protective antigen candidates. Immunoblotting of the expressed amino- and carboxy-terminal halves of one of the POMPs with postabortion sheep sera showed that the major humoral immune response appeared to be directed solely against the amino-terminal half. This result, in combination with the positive immunofluorescence staining of S26/3-infected cells using POMP-specific (specific to the amino-terminal half of the proteins) monoclonal antibodies, suggests the probable surface localization of the POMPs and, more specifically, the surface exposure of the amino-terminal half of these proteins. The four pomp genes are highly homologous, sharing 82 to 100% similarity with each other (two of the genes are identical). Genes with strong and weak homologies were also detected in C. psittaci avian and feline pneumonitis strains, respectively. No pomp homologs were found in strains of C. trachomatis and C. pneumoniae, but this does not preclude their existence. The absence of homology with various subtypes of C. pecorum, which complicate the diagnosis of the ovine abortion subtype, indicates the possible suitability of the these 90-kDa proteins as serodiagnostic antigens.

Amino Acid Sequence↗

PubMed1998

Impact of improved glycaemic control on rates of hypoglycaemia in insulin dependent diabetes mellitus.

Increased emphasis on strict glycaemic control of insulin dependent diabetes mellitus (IDDM) in young patients may be expected to cause increases in rates of significant hypoglycaemia. To evaluate whether this is the case for a large population based sample of IDDM children and adolescents rates of severe (coma, convulsion) and moderate (requiring assistance for treatment) hypoglycaemia were studied prospectively over a four year period. A total of 709 patients were studied yielding 2027 patient years of data (mean (SD) age: 12.3 (4.4); range 0-18 years, duration IDDM: 4.9 (3.8) years). Details of hypoglycaemia were recorded at clinic visits every three months when glycated haemoglobin (HbA1c) was also measured. Overall the incidence of severe hypoglycaemia was 7.8 and moderate was 15.4 episodes/100 patient years. Over the four years mean (SD) clinic HbA1c steadily fell from 10.2 (1.6)% in 1992 to 8.8 (1.5)% in 1995. In parallel with this there was a dramatic increase in the rate of hypoglycaemia, especially in the fourth year of the study, when severe hypoglycaemia increased from 4.8 to 15.6 episodes/100 patient years. This increase was particularly marked in younger children (< 6 years) in whom severe hypoglycaemia increased from 14.9 to 42.1 episodes/100 patient years in 1995. It is concluded that attempts to achieve improved metabolic control must be accompanied by efforts to minimise the effects of significant hypoglycaemia, particularly in the younger age group.

Adolescent↗

PubMed1997

Gender differences in the relation between depressive symptoms and alcohol problems: a longitudinal perspective.

Longitudinal relations between depressive symptoms and alcohol problems have been examined infrequently in community-based studies, and gender-specific findings to date appear to be inconclusive. Study hypotheses were that depressive symptoms predicted subsequent alcohol problems for females, whereas alcohol problems predicted subsequent depressive symptoms for males. The authors examined these relations in a random sample of household adults (aged 19 years or more) from Erie County, New York, assessed in 1986, 1989, and 1993 (n = 1,306). Measures of alcohol problems (in the previous year) incorporated an alcohol abuse/dependence diagnosis and a heavy alcohol use index. The Center for Epidemiologic Studies Depression Scale was used to assess depressive symptoms over a 1-month time frame. Comprehensive logistic regression models incorporated prior depressive symptoms, prior alcohol problems and sociodemographic variables (age, race, education, marital status, employment, total family income, and number of children living at home). For females, depressive symptoms predicted subsequent alcohol problems over 3 years (odds ratio = 3.04, 95% confidence interval 1.35-6.80, p < 0.01) and 4 years (odds ratio = 2.42, 95% confidence interval 1.14-5.12, p < 0.05), but not for 7 years. There was no evidence to support the hypothesis for males. This study clarifies and extends prior investigations of relations between these two prevalent mental health problems in a community-based sample.

Adolescent↗

PubMed1997

Test-retest reliability of the cognitive lifetime drinking history.

A new measure of lifetime alcohol consumption, the Cognitive Lifetime Drinking History (CLDH) uses beverage-specific questions on drink sizes and assesses drinking patterns to enhance recall. Two methods of establishing drinking intervals were examined: 1) floating--the respondent's report of when drinking changed, and 2) fixed--defined in terms of decades. Test-retest reliability for lifetime ounces of alcohol consumed and times intoxicated in lifetime estimated at visits 1 week or more apart was assessed in postmyocardial infarction patients (n = 81) and controls (n = 138) who had had at least 12 drinks in a year during their lifetimes. No significant differences in estimates of lifetime ounces of alcohol or times intoxicated were observed. Spearman's r ranged between 0.85 and 0.92 for the floating and fixed versions of the CLDH administered at a single visit and between 0.74 and 0.85 for the floating or fixed administered at both visits. Time between visits did not influence correlations. Intervals reported on the floating CLDH were comparable for postmyocardial infarction patients and controls. It took approximately 5 minutes longer to administer the floating CLDH than the fixed CLDH. Findings support use of the CLDH for case-control studies and suggest that the floating and fixed versions would yield comparable results.

Adult↗

PubMed1997

Mechanism and prevention of neurotoxicity caused by beta-amyloid peptides: relation to Alzheimer's disease.

In Alzheimer's disease, neurotoxic beta-amyloid peptides cause a deleterious influx of calcium ions into neurons. This increase in [Ca2+]int is expected to trigger intracellular events that eventually cause cell dysfunction and cell death. We find that the aggregated beta-amyloid peptide beta AP25-35 opens irreversibly a Ca(2+)-carrying channel, as does aggregated beta AP1-42. The opening of this channel is unaffected by DL-AP5, but it is blocked by Mg2+, CNQX and DNQX, suggesting a non-NMDA channel. External calcium enters and cytosolic calcium levels rise several-fold, as measured by fura-2 ratiometric analysis. Our findings illustrate a very early molecular event in the neurotoxicity of Alzheimer's disease. To combat the neurotoxic effect of aggregated beta-amyloid peptides, we have devised a series of very short antagonistic peptides. Using a combinatorial library of hexapeptides made from D-amino acids, we have selected peptides by their ability to complex with the tagged beta-amyloid peptide beta AP25-35. Certain of these so-called 'decoy peptides', as well as some modified decoy peptides, are able to abolish the calcium influx caused by aggregated, probably fibrillar, beta-amyloid peptides beta AP25-35 and beta AP1-42.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1997

Progression of borderline increases in albuminuria in adolescents with insulin-dependent diabetes mellitus.

We aimed to determine the natural history of borderline increases in albuminuria in adolescents with insulin-dependent (Type 1) diabetes mellitus (IDDM) and factors which are associated with progression to persistent microalbuminura. Fifty-five normotensive adolescents with IDDM and intermittent microalbuminura (overnight albumin excretion ratte of 20-200 micrograms min-1 on one of three consecutive timed collections, n = 29) or borderline albuminura (mean overnight albumin excretion rate of 7.2-20 micrograms min-1 on one of three consecutive timed collections, n = 30) were followed prospectively at 3 monthly intervals. The endpoint was persistent microalbuminuria defined as a minimum of three of four consecutive overnight albumin excretion rates of greater than 20 micrograms min-1. One hundred and forty-two adolescents with IDDM and normoalbuminura were also followed prospectively. Fifteen of the 59 patients (25.4%) with intermittent (9/29) or borderline (6/30) albuminura progressed to persistent microalbuminura (progressors) over 28 (15-50) months [median (range)] in comparison with two of the 142 patients with normoalbuminuria at entry (relative risk = 12.6; p = 0.001). Progressors to persistent microalbuminura were pubertal and had higher systolic (p = 0.02) and diastolic (p = 0.02) blood pressure, and HbA1c (p = 0.004) than non-progressors. All patients remained normotensive. Glomerular filtration rate, apolipoproteins, dietary phosphorus, protein and sodium intakes, and prevalence of smoking did not differ between progressors and non-progressors. Total renin was higher in the diabetic patients without a difference between progressors and non-progressors. In conclusion there is a relatively high rate of progression to persistent microalbuminuria in pubertal adolescents with borderline increases in albuminura and duration greater than 3 years. These patients require attention to minimize associated factors of poor metabolic control and higher blood pressure in the development of incipient nephropathy.

Adolescent↗

PubMed1997

Molecular cloning and characterisation of a putative aspartate proteinase associated with a gut membrane protein complex from adult Haemonchus contortus.

A cDNA was isolated from an adult Haemonchus contortus cDNA expression library the deduced amino acid sequence of which showed significant homology to mammalian pepsinogen sequences. The library was screened with antisera raised against Haemonchus galactose-containing glycoprotein complex, a gut membrane protein complex with aspartyl proteinase activity which has shown considerable potential as a protective antigen. The amino acid sequence obtained corresponded very closely in part to the N-terminal amino acid sequences of two polypetides within the complex. The enzyme was shown to be almost exclusively expressed by the blood-feeding parasite stages. The cDNA was expressed in E. coli, and antibody produced to the recombinant protein bound to the luminal surface of the gut in the adult parasite. The proteinase may play a central role in digesting the blood meal and is considered a potential sub-unit vaccine candidate.

Amino Acid Sequence↗

PubMed1997

Expression of the Zn finger gene, EVI-1, in acute promyelocytic leukemia.

The EVI-1 gene encodes a Zn finger, DNA binding protein previously detected in some acute myelogenous leukemias (AML) and myelodysplasias (MDS), but not in normal marrow or cord blood cells. Experimental studies suggest EVI-1 blocks cellular differentiation by binding to GATA-1 or other specific DNA sequences controlling gene expression, and may be involved in the pathogenesis of some AMLs. To further define potential roles for EVI-1 in leukemia pathogenesis, we studied its regulation in acute promyelocytic leukemias (APL). Seven of 11 APL cases expressed EVI-1 RNA detected by RNA PCR at diagnosis, and expression was detected in two additional cases after treatment with all-trans retinoic acid (ATRA). Two of four cases studied at relapse also expressed EVI-1 RNA. To investigate regulation of EVI-1 expression in APL, we examined its expression in the NB4 APL cell line. NB4 cells did not express EVI-1 under basal conditions, but expressed EVI-1 after ATRA-induced differentiation. When NB4 cells were exposed to ATRA and transferred to cultures with N,N'-hexamethylene-bis-acetamide (HMBA), differentiation occurred but EVI-1 RNA was not detected, indicating that EVI-1 expression was not required for terminal, NB4 differentiation. ATRA-resistant NB4 cells were obtained by continuous culture in gradually increasing concentrations of ATRA. These cells did not express markers of differentiation but continued to express EVI-1 for several weeks even after ATRA withdrawal. To assess whether expression of the APL PML-RAR alpha fusion gene alone was sufficient for ATRA induction of EVI-1, the PML-RAR alpha gene cDNA was expressed in U937 histiocytic lymphoma cells. ATRA treatment of PML-RAR alpha-transfected or control U937 cells did not induce EVI-1 expression. In conclusion, this study demonstrates the EVI-1 gene is consistently expressed in APL cells either constitutively or after ATRA treatment. ATRA represents the first biologically active agent shown to specifically regulate EVI-1 expression in blood cells. In contrast to previous studies in AML and MDS, the pattern of EVI-1 expression suggests it may facilitate rather than inhibit myeloid differentiation during ATRA treatment. However, effects of EVI-1 expression are likely to be complex, and expression in ATRA-resistant APL cells may indicate multiple roles for this gene.

Acetamides↗

PubMed1997

Assessment of cytochrome P450 3A4 activity during the menstrual cycle using alfentanil as a noninvasive probe.

BACKGROUND: Gender-dependent differences in cytochrome P450 activity, drug metabolism, drug elimination, and their clinical consequences are increasingly apparent. P450 3A4 is the most abundant P450 isoform in the human liver and is responsible for metabolizing a vast and diverse assortment of therapeutic agents, including opioids, benzodiazepines, and local anesthetics. P450, 3A4 activity is higher in women, influenced by steroid hormone levels, and is speculated to vary during the menstrual cycle. This investigation tested the hypothesis that P450 3A4 activity varies during the menstrual cycle. Alfentanil clearance was used as a metabolic probe for P450 3A4 activity. METHODS: Alfentanil (20 micrograms/kg bolus) was administered to nine nonsmoking, nonpregnant female volunteers (age, 26 +/- 5 yr) with normal menstrual cycles on three separate occasions during the same menstrual cycle: days 2 (menstrual phase), 13 (estrogen peak), and 21 (progesterone peak). Venous plasma alfentanil concentrations were determined by gas chromatography-mass spectrometry. Alfentanil clearance was determined by noncompartmental methods and by a three-compartment model with both pooled population and two-stage analysis. RESULTS: There was no significant difference in any measure of alfentanil clearance. Noncompartmental clearances (mean +/- SD) were 3.62 +/- 0.76, 3.81 +/- 0.96, and 3.60 +/- 0.84 ml/kg/ min, respectively, on days 2, 13, and 21 of the menstrual cycle. CONCLUSIONS: Alfentanil clearances were not different on menstrual cycle days 2, 13, and 21, strongly suggesting no change in P450 3A4 activity. Menstrual cycle differences in alfentanil clearances do not contribute to interindividual variability in alfentanil disposition in women. If other P450 3A4 substrates are comparable, then menstrual cycle variability in their metabolism may not be a consideration in dosing or in the design of pharmacokinetic investigations.

Adolescent↗

PubMed1997

The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions.

BACKGROUND: There is considerable unexplained variability in alfentanil pharmacokinetics, particularly systemic clearance. Alfentanil is extensively metabolized in vivo, and thus systemic clearance depends on hepatic biotransformation. Cytochrome P450 3A4 was previously shown to be the predominant P450 isoform responsible for human liver microsomal alfentanil metabolism in vitro. This investigation tested the hypothesis that P450 3A4 is responsible for human alfentanil metabolism and clearance in vivo. METHODS: Nine healthy male volunteers who provided institutionally approved written informed consent were studied in a three-way randomized crossover design. Each subject received alfentanil (20 micrograms/kg given intravenously) 30 min after midazolam (1 mg injected intravenously) on three occasions: control; high P450 3A4 activity (rifampin induction); and low P450 3A4 activity (selective inhibition by troleandomycin). Midazolam is a validated selective in vivo probe for P450 3A4 activity. Venous blood was sampled for 24 h and plasma concentrations of midazolam and alfentanil and their primary metabolites 1'-hydroxymidazolam and noralfentanil were measured by gas chromatography-mass spectrometry. Pharmacokinetic parameters were determined by two-stage analysis using both noncompartmental and three-compartment models. RESULTS: Plasma alfentanil concentration-time profiles depended significantly on P450 3A4 activity. Alfentanil noncompartmental clearance was 5.3 +/- 2.3, 14.6 +/- 3.8, and 1.1 +/- 0.5 ml.kg-1.min-1, and elimination half-life was 58 +/- 13, 35 +/- 7, and 630 +/- 374 min, respectively, in participants with normal (controls), high (rifampin), and low (troleandomycin) P450 3A4 activity (means +/- SD; P < 0.05 compared with controls). Multicompartmental modeling suggested a time-dependent inhibition-resynthesis model for troleandomycin effects on P450 3A4 activity, characterized as k10(t) = k10[1-phi e-alpha(t-tzero)], where k10(t) is the apparent time-dependent rate constant, k10 is the uninhibited rate constant, phi is the fraction of P450 3A4 inhibited, and alpha is the apparent P450 3A4 reactivation rate. Alfentanil clearance was calculated as V1 k10 for controls and men receiving rifampin, and as V1.average k10(t) for men receiving troleandomycin. This clearance was 4.9 +/- 2.1, 13.2 +/- 3.6, and 1.5 +/- 0.8 ml.kg-1.min-1, respectively, in controls and in men receiving rifampin or troleandomycin. There was a significant correlation (r = 0.97, P < 0.001) between alfentanil systemic clearance and P450 3A4 activity. CONCLUSIONS: Modulation of P450 3A4 activity by rifampin and troleandomycin significantly altered alfentanil clearance and disposition. These results strongly suggest that P450 3A4 is the major isoform of P450 responsible for clinical alfentanil metabolism and clearance. This observation, combined with the known population variability in P450 3A4 activity, provides a mechanistic explanation for the interindividual variability in alfentanil disposition. Furthermore, known susceptibility of human P450 3A4 activity to induction and inhibition provides a conceptual framework for understanding and predicting clinical alfentanil drug interactions. Finally, human liver microsomal alfentanil metabolism in vitro is confirmed as an excellent model for human alfentanil metabolism in vivo.

Adult↗

PubMed1997

Comparison of serotonin receptor numbers and activity in specific hypothalamic areas of sexually active and inactive female rats.

In a previous study we have shown that a positive correlation exists between 5-hydroxytryptamine (5-HT) activity and female sexual receptivity in the pre-optic area (POA) and median eminence (ME) and that there is a negative correlation in the ventromedial nucleus (VMN), zona incerta (ZI) and arcuate nucleus (ARC). In this report, the possibility that 5-HT receptor density and affinity alter with sexual receptivity has been investigated. Micropunches of the POA, VMN, ARC, ME and the anterior hypothalamus were dissected from ovariectomised rats primed with a submaximal steroid regime (2 microg oestradiol benzoate, OB, followed at 48 h by 0.05 mg progesterone) which induced receptivity (lordosis quotient, LQ, 80-100%) in approximately half the animals, the remaining half usually exhibiting an LQ <20%. Binding studies were carried out using 3H-ketanserin (5-HT2A ligand) and 3H-8-hydroxy-2-(di-n-propylamine)tetraline (8-OHDPAT; 5-HT1A ligand) and pooled (n = 5) micropunch samples. The Bmax of 5-HT2A receptors in the sexually receptive groups was significantly (p < 0.05) greater in the POA and ME and significantly lower in the VMN, ARC and ZI when compared with values in the non-receptive animals. The KD values of the 5-HT2A receptors did not differ in the two groups (except the ZI, where the KD was lower in receptive rats). Neither the Bmax nor KD of the 5-HT1A receptors differed in the two groups in any area investigated. Administration of the 5-HT2 agonists dimethoxyiodophenylaminopropane and m-chlorophenyl piperazine into the POA resulted in enhanced sexual activity in animals exhibiting a low level of receptivity, after 5 microg OB given alone while ketanserin (5-HT2A antagonist) in the POA inhibited sexual activity in receptive animals primed with the submaximal steroid regime given above. In the same models, neither the 5-HT2 agonists nor the 5-HT2A antagonist affected behaviour when applied to the VMN. The 5-HT1A agonist 8-OHDPAT exerted an inhibitory effect in the VMN. These findings, together with earlier results, show that in receptive animals there is an increase in both 5-HT turnover and 5-HT2A receptors in the POA and ME. Additionally 5-HT2 agonists and an antagonist applied to the POA enhance and reduce sexual activity, respectively. This suggests that the 5-HT2 system in the POA has a stimulatory role in the control of female sexual behaviour. Both 5-HT activity and 5-HT2 receptors are decreased in the VMN, ARC and ZI of receptive animals. 5-HT2 agonists and a 5-HT2A antagonist have no effect in the VMN indicating that there is no 5-HT2-stimulatory or -inhibitory effect in this area, at least in the animal models used in these experiments. However, the VMN is a site of an inhibitory action mediated by the 5-HT1A receptors.

Animals↗

PubMed1997

The PerFect lipid optimizer kit for maximizing lipid-mediated transfection of eukaryotic cells.

The transfection efficiencies of a panel of eight uniquely different lipid reagents has been evaluated with two other commercially available lipids for use in transfecting a diversity of eukaryotic cell lines. The PerFect lipids are available individually or together in an optimization panel format that can be tested in any given cell line, enabling one to evaluate the optimal lipid for transfecting each individual cell line. Our results demonstrate that no single lipid is optimal for plasmid transfection over a broad range of cell types, thus emphasizing the need for multiple unique lipid reagents and a simple format for testing their transfection efficiency on a given cell type.

3T3 Cells↗