Parental Psychological Control and Self-Efficacy as Predictors of Romantic Relationship Power Dynamics.

In the current study, we utilized a person-centered approach to examine the relations of parental psychological control (PPC) and relationship self-efficacy (RSE) to power dynamics in emerging adults' romantic relationships. College student emerging adults (N = 312) completed measures assessing retrospective PPC, RSE, and perceived self and partner power in current relationships. Latent profile analysis uncovered four relationship types based on reported self- and partner-power: balanced-unified, balanced-interchanging, unbalanced-high self, and unbalanced-high partner. Increases in PPC were related to increased odds of being in an unbalanced relationship. Higher levels of RSE were associated with decreased odds of being in an unbalanced relationship. Further, even individuals in the balanced profile who reported average levels of both self and partner power (balanced-interchanging) reported higher levels of PPC and lower levels of RSE compared to those in the balanced group where levels of both self and partner power were low (balanced-unified). These findings suggest using a person-centered approach to relationship power may advance our conceptualization of power distribution in romantic relationships. Further, experienced family dynamics and one's sense of self may be especially important for young adults' tendency to form healthy relationships. The current findings encourage future investigation into the mechanisms by which parental factors predict both dominance and submissiveness in romantic relationships. Understanding predictors of power dynamics may contribute to intimate partner violence prevention and intervention.

Costs of illness due to endemic cholera.

Economic analyses of cholera immunization programmes require estimates of the costs of cholera. The Diseases of the Most Impoverished programme measured the public, provider, and patient costs of culture-confirmed cholera in four study sites with endemic cholera using a combination of hospital- and community-based studies. Families with culture-proven cases were surveyed at home 7 and 14 days after confirmation of illness. Public costs were measured at local health facilities using a micro-costing methodology. Hospital-based studies found that the costs of severe cholera were US$32 and US$47 in Matlab and Beira. Community-based studies in North Jakarta and Kolkata found that cholera cases cost between US$28 and US$206, depending on hospitalization. Patients' cost of illness as a percentage of average monthly income were 21% and 65% for hospitalized cases in Kolkata and North Jakarta, respectively. This burden on families is not captured by studies that adopt a provider perspective.

Mechanism of ritonavir changes in methadone pharmacokinetics and pharmacodynamics: II. Ritonavir effects on CYP3A and P-glycoprotein activities.

Ritonavir diminishes methadone plasma concentrations, an effect attributed to CYP3A induction, but the actual mechanisms are unknown. We determined short-term (2-day) and steady-state (2-week) ritonavir effects on intestinal and hepatic CYP3A4/5 (probed with intravenous (IV) and oral alfentanil (ALF) and with miosis) and P-glycoprotein (P-gp) (fexofenadine), and on methadone pharmacokinetics and pharmacodynamics in healthy volunteers. Acute ritonavir increased the area under the concentration-time curve (AUC)(0-infinity)/dose ratio (ritonavir/control) for oral ALF 25-fold. Steady-state ritonavir increased the AUC(0-Infinity)/dose ratio for IV and oral ALF 4- and 10-fold, respectively; reduced hepatic extraction (from 0.26 to 0.07) and intestinal extraction (from 0.51 to 0); and increased bioavailability (from 37 to 95%). Acute ritonavir inhibits first-pass CYP3A > 96%. Chronic ritonavir inhibits hepatic CYP3A (> 70%) and first-pass CYP3A (> 90%). Acute and steady-state ritonavir increased the fexofenadine AUC(0-infinity) 2.8- and 1.4-fold, respectively, suggesting P-gp inhibition. Steady-state compared with acute ritonavir caused mild apparent induction of P-gp and hepatic CYP3A, but net inhibition still predominated. Ritonavir inhibited both intestinal and hepatic CYP3A and drug transport. ALF miosis noninvasively determined CYP3A inhibition by ritonavir.

Mechanism of ritonavir changes in methadone pharmacokinetics and pharmacodynamics: I. Evidence against CYP3A mediation of methadone clearance.

Ritonavir diminishes methadone plasma concentrations, an effect attributed to CYP3A induction, but the actual mechanisms are unknown. We determined ritonavir effects on stereoselective methadone pharmacokinetics and clinical effects (pupillary miosis) in healthy human immunodeficiency virus-negative volunteers. Subjects received intravenous plus oral (deuterium-labeled) racemic methadone after no ritonavir, short-term (3-day) ritonavir, and steady-state ritonavir. Acute and steady-state ritonavir, respectively, caused 1.5- and 2-fold induction of systemic and apparent oral R- and S-methadone clearances. Ritonavir increased renal clearance 40-50%, and stereoselectively (S > R) increased hepatic methadone N-demethylation 50-80%, extraction twofold, and clearance twofold. Bioavailability was unchanged despite significant inhibition of intestinal P-glycoprotein. Intestinal and hepatic CYP3A was inhibited > 70%. Ritonavir shifted methadone plasma concentration-miosis curves leftward and upward. Rapid ritonavir induction of methadone clearance results from increased renal clearance and induced hepatic metabolism. Induction of methadone metabolism occurred despite profound CYP3A inhibition, suggesting no role for CYP3A in clinical methadone metabolism and clearance. Ritonavir may alter methadone pharmacodynamics.

Influence of CYP3A5 genotype on the pharmacokinetics and pharmacodynamics of the cytochrome P4503A probes alfentanil and midazolam.

The hepatic and first-pass cytochrome P4503A (CYP3A) probe alfentanil (ALF) is also metabolized in vitro by CYP3A5. Human hepatic microsomal ALF metabolism is higher in livers with at least one CYP3A5*1 allele and higher CYP3A5 protein content, compared with CYP3A5*3 homozygotes with little CYP3A5. The influence of CYP3A5 genotype on ALF pharmacokinetics and pharmacodynamics was studied, and compared to midazolam (MDZ), another CYP3A probe. Healthy volunteers (58 men, 41 women) were genotyped for CYP3A5 *1, *3, *6, and *7 alleles. They received intravenous MDZ then ALF, and oral MDZ and ALF the next day. Plasma MDZ and ALF concentrations were determined by mass spectrometry. Dark-adapted pupil diameters were determined coincident with blood sampling. In CYP3A5(*)3/(*)3 (n=62), (*)1/(*)3 (n=28), and (*)1/(*)1 (n=8) genotypes, systemic clearances of ALF were 4.6+/-1.8, 4.8+/-1.7, and 3.9+/-1.7 ml/kg/min and those of MDZ were 7.8+/-2.3, 7.7+/-2.3, and 6.0+/-1.4 ml/kg/min, respectively (not significant), and apparent oral clearances were 11.8+/-7.2, 13.3+/-6.1, and 12.6+/-8.2 ml/kg/min for ALF and 35.2+/-19.0, 36.4+/-15.7, and 29.4+/-9.3 ml/kg/min for MDZ (not significant). Clearances were not different between African Americans (n=25) and Whites (n=68), or between CYP3A5 genotypes within African Americans. ALF pharmacodynamics was not different between CYP3A5 genotypes. There was consistent concordance between ALF and MDZ, in clearances and extraction ratios. Thus, in a relatively large cohort of healthy subjects with constitutive CYP3A activity, CYP3A5 genotype had no effect on the systemic or apparent oral clearances, or pharmacodynamics, of the CYP3A probes ALF and MDZ, despite affecting their hepatic microsomal metabolism.

Database of Optimized Proteomic Quantitative Methods for Human Drug Disposition-Related Proteins for Applications in Physiologically Based Pharmacokinetic Modeling.

The purpose of this study was to create an open access repository of validated liquid chromatography tandem mass spectrometry (LC-MS/MS) multiple reaction monitoring (MRM) methods for quantifying 284 important proteins associated with drug absorption, distribution, metabolism, and excretion (ADME). Various in silico and experimental approaches were used to select surrogate peptides and optimize instrument parameters for LC-MS/MS quantification of the selected proteins. The final methods were uploaded to an online public database (QPrOmics; www.qpromics.uw.edu/qpromics/assay/), which provides essential information for facile method development in triple quadrupole mass spectrometry (MS) instruments. To validate the utility of the methods, the differential tissue expression of 107 key ADME proteins was characterized in the tryptic digests of the pooled subcellular fractions of human liver, kidneys, intestines, and lungs. These methods and the data are critical for development of physiologically based pharmacokinetic (PBPK) models to predict xenobiotic disposition.

Mutational and structural analyses of the regulatory protein B of soluble methane monooxygenase from Methylococcus capsulatus (Bath).

BACKGROUND: The soluble methane monooxygenase (sMMO) system in methanotrophic bacteria uses three protein components to catalyze the selective oxidation of methane to methanol. The coupling protein B (MMOB) both activates the carboxylate-bridged diiron center in the hydroxylase (MMOH) for substrate oxidation and couples the reaction to electron transfer from NADH through the sMMO reductase. Although the X-ray structure of the hydroxylase is known, little structural information is available regarding protein B. RESULTS: Wild-type protein B from Methylococcus capsulatus (Bath) is very susceptible to degradation. The triple mutant protein B, Gly10-->Ala, Gly13-->Gln, Gly16-->Ala is resistant to degradation. Analyzing wild-type and mutant forms of protein B using size exclusion chromatography and circular dichroism spectroscopy suggests that the amino terminus of MMOB (Ser1-Ala25) is responsible for the proteolytic sensitivity and unusual mobility of the protein. We used the stable triple glycine protein B mutant to generate an affinity column for the hydroxylase and investigated the interaction between MMOH and MMOB. These results suggest the interaction is dominated by hydrophobic contacts. CONCLUSIONS: A structural model is presented for protein B that explains both its proclivity for degradation and its anomalous behavior during size exclusion chromatography. The model is consistent with previously published biophysical data, including the NMR structure of the phenol hydroxylase regulatory protein P2. Furthermore, this model allows for detailed and testable predictions about the structure of protein B and the role of proposed recognition sites for the hydroxylase.

A primary care-based needs assessment of people with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a common cause of chronic progressive neurological disability where reduction in quality of life is an important feature. Many GPs have MS patients with a range of disabilities. Little is known about the supply of medical and community services and how this compares with demand. AIM: We aim to describe a community based sample of MS patients and investigate how disease characteristics, benefits, services accessed and perceived needs relate to sense of wellbeing. DESIGN: Cross-sectional survey. SETTING: Participants were recruited from a representative network of 30 GP practices across Northern Ireland. METHOD: MS patients answered a professionally administered questionnaire and agreed to their medical records being examined. Information was collected about their medical condition, sociodemographic characteristics, receipt of benefits and services, perceived needs and sense of wellbeing. RESULTS: Of the 149 participants, 23% were mildly affected (Kurtzke's Expanded Disability Status Scale [EDSS] 0-4.5), 41% were moderately disabled (EDSS 5.0-6.5) and 36% were severely disabled (EDSS 7.0-9.5). Disability was related to employment, receipt of benefits and services. Physiotherapy was a commonly perceived need. Other perceived needs differed between the moderately and severely disabled groups. Scores relating to wellbeing were related to disability and perceived needs. CONCLUSIONS: The relationship between use of medical and community services and disability is important for planning service provision. We have shown that perceived needs are related to wellbeing. In a progressive illness these developing needs could be anticipated.

The use of in vivo fluorescence image sequences to indicate the occurrence and propagation of transient focal depolarizations in cerebral ischemia.

A method for the detection and tracking of propagated fluorescence transients as indicators of depolarizations in focal cerebral ischemia is described, together with initial results indicating the potential of the method. The cortex of the right cerebral hemisphere was exposed for nonrecovery experiments in five cats anesthetized with chloralose and subjected to permanent middle cerebral artery (MCA) occlusion. Fluorescence with 370-nm excitation (attributed to the degree of reduction of the NAD/H couple) was imaged with an intensified charge-coupled device camera and digitized. Sequences of images representing changes in gray level from a baseline image were examined, together with the time courses of mean gray levels in specified regions of interest. Spontaneous increases in fluorescence occurred, starting most commonly at the edge of areas of core ischemia; they propagated usually throughout the periinfarct zone and resolved to varying degrees and at varying rates, depending on proximity of the locus to the MCA input. When a fluorescence transient reached the anterior cerebral artery territory, its initial polarity reversed from an increase to a decrease in fluorescence. An initial increase in fluorescence in response to the arrival of a transient may characterize cortex that will become infarcted, if pathophysiological changes in the periinfarct zone are allowed to evolve naturally.

Effects of electrical stimulation of the pontine A5 cell group on blood pressure and heart rate in the rabbit.

The effects of electrical stimulation of the A5 noradrenergic cell group of the ventrolateral pons was assessed in rabbits. Stimulation administered through either concentric bipolar or monopolar electrodes produced current-intensity related increases in mean arterial pressure (MAP). Decreases in heart rate (HR) accompanied the increases in MAP, but were essentially eliminated by bilateral vagotomy or destruction of the nucleus and tractus solitarii (NTS), thereby indicating that the HR decelerations were secondary to activation of baroreceptor reflexes. Neither vagotomy nor midcollicular section of the brainstem altered the MAP response to A5 stimulation. Bilateral destruction of the NTS slightly enhanced the response. Several rabbits received microinjections of 6-hydroxydopamine (6-OHDA) into the A5 region 2 weeks before the experiment. Other rabbits received vehicle injections and served as control subjects for the non-specific effects of the 6-OHDA injections. 6-OHDA injections, but not vehicle injections, prevented the vasopressor effects of A5 stimulation. However, stimulation of the A1 noradrenergic nucleus of the ventrolateral medulla produced decreases in MAP in rabbits given prior microinjections of 6-OHDA into A5. These observations are interpreted to indicate that the 6-OHDA injections produced neurotoxic effects which were relatively restricted to the A5 region. Furthermore, the data from all of these experiments are interpreted as indicating that the vasopressor effects observed as a consequence of electrical stimulation of A5 are due to excitation of the noradrenaline-containing neuron cell bodies of this region and that this effect is mediated via pathways arising from this region and terminating in the intermediolateral cell column of the spinal cord.

Embryonic hippocampal grafts ameliorate the deficit in DRL acquisition produced by hippocampectomy.

Transplants of fetal neural tissue survive and develop in lesion cavities produced in adult rats. The present experiment tested the effect of grafting fetal hippocampal or brainstem tissue on the ability of rats with hippocampal lesions to perform on a differential reinforcement of low response rate (DRL) operant schedule. The DRL interval was 20s. Eighty-six percent of the hippocampal grafts and 69% of the brainstem grafts developed to maturity. Inspection of sections from rats in which the mature transplant had been injected with Fast blue, indicated that these grafts formed connections with the host brain. Consistent with previous reports, rats with hippocampal lesions were impaired in performance of the DRL task. Rats given fetal grafts of hippocampal tissue into the hippocampal lesion site on the day of lesion production were significantly better in performance of the DRL requirement than were lesion-only rats or rats receiving grafts of fetal brainstem tissue. The results of this study confirm that grafts of fetal brain tissue can both develop in a lesion site in an adult brain and ameliorate lesion-induced behavioral deficits.

The motor innervation of the single-bellied digastric muscle in the rabbit: a retrograde horseradish peroxidase study.

The digastric muscle of the rabbit consists of a single anterior belly which inserts onto the lower jaw. Horseradish peroxidase was injected into the muscle and into subcutaneous regions overlying the lower jaw to determine the sites of origin of the motor innervation to both the digastric muscle and the platysma muscles. After digastric muscle injection, labelled cells were found in the ipsilateral retrotrigeminal nucleus as well as in the intermediate subnucleus of the main facial nucleus on both sides. Subcutaneous injections produced labelling which was found bilaterally in the intermediate subnucleus and in the ventromedial portion of the medial subnucleus. These results are interpreted in relation to the common embryological origin of these two muscles and their innervation.

The effects of stimulation of the A5 region on blood pressure and heart rate in rabbits.

The effects of stimulation of the A5 cell group of the caudal ventrolateral pons electrically or with L-glutamate on heart rate and blood pressure were determined in rabbits. Electrical stimulation caused blood pressure increases and reflex bradycardia. L-glutamate caused decreases in blood pressure and heart rate which were blocked by the L-glutamate antagonist aminophosphoheptanoic acid. Transection of the brainstem at the level of the midbrain did not alter the effects of either electrical or chemical stimulation. Lesions of the nucleus and tractus solitarius (NTS) attenuated the effects of L-glutamate, but did not change the effectiveness of electrical stimulation. Injections of 6-hydroxydopamine three to four weeks before the experiments blocked the effects of electrical stimulation but only reduced the effects of L-glutamate injection. The A5 group may have two functional subdivisions. Some A5 cells may produce blood pressure depressor and bradycardic effects by means of projections to the NTS and the spinal cord. Other A5 cells may produce blood pressure pressor effects by means of projections to the spinal cord.

The time-course of trimethyltin-induced fiber and terminal degeneration in hippocampus.

Trimethyltin (TMT) produces prominent neuron death in the hippocampus. The time-course of TMT-induced damage was studied using reduced-silver procedures for impregnation of degenerating axons and their terminals, and a modified Timm's stain procedure for visualization of hippocampal transitional metals. Standard cell body stains were also used. Fifty-four, adult, Long-Evans rats were gavaged with 6.0 mg TMT/kg b.wt. and 10 rats were gavaged with distilled water as controls. Five TMT-gavaged rats and one saline-gavaged rat were sacrificed on either postgavage day 1, 3, 6, 9, 14, 19, 30, 45, 70 or 99. Histological examination revealed a band of degenerating terminals in the stratum lucidum, below the hippocampal subfields CA3a,b pyramidal cells, by postgavage day 3. This preceded dentate gyrus granule cell loss supplying the mossy fiber input to the stratum lucidum by several days. Hippocampal pyramidal cell necrosis continued through the examination period while dentate granule cell loss subsided between postgavage days 9 and 14. Fiber and terminal degeneration was more extensive in the dorsal hippocampus than in the ventral hippocampus, although Timm's-stained sections revealed "bleaching" of stainable metal in the mossy fiber pathway of the ventral hippocampus. These data suggest that loss of ventral dentate granule cells might reduce TMT-induced necrosis of pyramidal cells in the ventral (temporal) part of the Ammon's horn, possibly by preventing the spread of seizure activity in this region of the hippocampus. Additionally, although previous studies have reported the toxic effects of TMT to last approximately 60 days, the results of the present study indicate that TMT-induced degeneration continues for more than 3 months. Reduced-silver stains, such as the Fink-Heimer procedure, appear to be more sensitive indicators of enduring neuropathology than more traditional cell stains.

Evaluation of site and age of weaning on pig growth performance.

Site-segregated early weaning (SSEW) refers to the practice of weaning pigs from the sow at an early age and placing them in a nursery that is physically isolated from the breeding herd. An experiment involving 369 pigs was conducted at the Prairie Swine Center to investigate the impact of SSEW on pig performance when the herd of origin has a high health status and when housing and management conditions are kept as similar as possible across weaning regime. Three treatments were compared: weaning at 21+/-3 d and keeping the pigs on-site in an all-in-all-out nursery room (Control), weaning at 12+/-2 d of age and keeping the pigs on-site in a separate but identical all-in-all-out nursery room (OSEW), or weaning at 12+/-2 d of age and moving the pigs off-site to an all-in-all-out nursery room located 16 km from the Center (SSEW). Ventilation, feed, penning, feeders, and drinkers were kept as similar as possible for all treatments. Off-site weaning improved 56-d body weight (P < .05) by 12.5 and 8.3% compared with OSEW and Control, respectively. The improvement appeared to be the result of improvements primarily in feed intake but also due to enhanced efficiency of nutrient utilization. This experiment confirms that SSEW results in significant improvements in 56-d weights, even when the herd of origin has a relatively high health status.

Association of Phoma terrestris, Pythium irregulare, and Fusarium acuminatum in Causing Red Root Rot of Corn.

Greenhouse and field tests were conducted in 1992 and 1993 to determine the causal pathogen(s) of red root rot (RRR) of corn. Corn hybrids Dekalb DK 522, DK 572, DK 677, and DK 582 were utilized. Phoma terrestris, Pythium irregulare, and Fusarium acuminatum were used alone or in combination to infest potting mix in greenhouse tests or soil in field tests. Results indicated that P. terrestris is the primary pathogen in the RRR complex of corn in Delaware. When P. terrestris and Pythium irregulare were associated, the disease progressed faster and was more severe, resulting in significantly higher (P ≤ 0.01) root rot, basal stalk rot, and wilt. F. acuminatum played a minor role in causing the disease, with little additional symptom development when combined with P. terrestris or Pythium irregulare.

Incidence of Phoma terrestris, Causal Agent of Red Root Rot, in Corn Roots and Soil in Delaware and on the Eastern Shore of Maryland.

Red root rot of corn (Zea mays L.) has caused sporadic disease losses in Delmarva during the past 6 years. A survey was made between 21 August and 14 September 1995 in 11 counties in Delaware and on the eastern shore of Maryland to detect Phoma terrestris (E. M. Hans.) in corn roots and in the surrounding soil. Sampling was based on one field per 1,200 ha of corn production in each county. Three root samples and one soil sample were collected from each of 100 corn production fields from corn plants with diseased basal stalk tissue. The presence of P. terrestris was confirmed by cultures from root samples that produced a beet-red color on Watson's sterile wheat straw agar (2). Serial dilutions of soil samples in 0.1% water agar were mixed with unsolidified Watson's basal medium, followed by amendment with a 2-(4-thiazolyl)benzimidazole solution (1). P. terrestris was detected in root samples from 99% of the fields surveyed and from 82% of the soil samples. Soil populations ranged from 0.2 to 200 CFU per g of soil, with a mean of 12.5 CFU. This survey indicated that P. terrestris is widespread in corn production fields in Delaware and on the eastern shore of Maryland. Disease symptoms in surveyed fields indicated that pathogenicity on corn is variable, generally does not result in serious losses, and is related to hybrid susceptibility and growing conditions. References: (1) B. Sneh et al. Phytopathology 64:275, 1974. (2) R. D. Watson. Plant Dis. Rep. 45:289, 1961.

Laboratory diagnosis of plague.

In response to an outbreak of a plague-like disease in India, the Public Health Laboratory Service (PHLS) in the UK distributed advice on the isolation and identification of Yersinia pestis. Some of the procedures outlined were evaluated using a number of isolates of Y. pestis, complemented with in-house techniques detecting virulence genes or their products. These laboratory investigations are limited in that they are either only indicative or they take too long (48 hours or more), and thus represent a serious delay to the patient. Successful patient management must be based on a case history, and therapy should be started immediately. Laboratory diagnosis will subsequently rule out most pathogens which cause similar infections, yet will still require confirmation by a reference laboratory.

A study of the justification for intensive tick control in Kenyan rangelands.

Sixty male weaner cattle at the National Range Research Station, Kiboko, Kenya were placed in four groups of 15 animals under four different tick control regimens for 16 months. The treatment groups were: spraying with acaricide weekly, spraying every three weeks, spraying whenever group mean tick infestations reached more than 200 per animal (once only in the course of the study) and a control unsprayed group. The cattle were weighed monthly. There were no significant differences between the liveweight gains of the groups during a period of severe drought and during the following period of compensatory weight gain. The untreated group gained more weight than the other groups. Cattle died in all groups, but without significant differences between the groups; the long drought and associated malnutrition were the prime cause of death. Rhipicephalus pravus and R pulchellus were the dominant tick species with fewer Amblyomma gemma, Hyalomma truncatum and small numbers of Boophilus decoloratus and R evertsi. These ticks transmit anaplasmosis, babesiosis and cowdriosis in the study area. Total tick counts reached 750 on individual animals but group means rarely reached more than 200 because of high resistance to ticks in some animals. Host resistance ranking within groups was virtually constant throughout the experiment. The study showed that intensive tick control is not required in the semi-arid areas of Africa.