bluuebunny/crossref_metadata_2025 huggingface dataset:
The Parent Supervision Attributes Profile Questionnaire: a measure of supervision relevant to children’s risk of unintentional injury
Authors: Morrongiello B A , Corbett M
Published: February 2006

Objective:To further establish the psychometric properties of the Parent Supervision Attributes Profile Questionnaire (PSAPQ), a questionnaire measure of parent supervision that is relevant to understanding risk of unintentional injury among children 2 through 5 years of age.

Methods:To assess test-retest reliability, parents completed the PSAPQ twice, with a one month interval. Internal consistency estimates for the PSAPQ were also computed. Confirmatory factor analyses were applied to the data to assess the four factor structure of the instrument by assessing the convergent and divergent validity of the subscales and their respective items.

Results:Test-retest reliability and internal consistency scores were good, exceeding 0.70 for all subscales. Factor analyses confirmed the hypothesized model—namely that the 29 item questionnaire comprised four unique factors: protectiveness, supervision beliefs, risk tolerance, and fate influences on child safety.

Conclusions:Previous tests comparing the PSAPQ with indices of actual supervision and children’s injury history scores revealed good criterion validity. The present assessment of the PSAPQ revealed good reliability (test-retest reliability, internal consistency) and established the convergent and divergent validity of the four factors. Thus, the PSAPQ has proven to have strong psychometric properties, making it a unique and useful measure for researchers interested in studying links between supervision and young children’s risks of unintentional injury.
Firearm suicide in New York City in the 1990s
Authors: Piper T M , Tracy M , Bucciarelli A , Tardiff K , Galea S
Published: February 2006

Objective:Across the US, firearms are used in approximately 60% of all suicide deaths. Little research has assessed the role and determinants of firearms in suicide in major urban areas.

Methods:The authors collected data on all suicide deaths between 1990 and 2000 from the Office of the Chief Medical Examiner of New York City (NYC) and assessed trends and correlates of firearm related suicide deaths.

Results:During the period studied, there were a total of 6008 suicides in NYC; 1200 (20.0%) were firearm related suicides. There was a decrease in total suicides, total firearm suicides, and the proportion of firearm related suicides. In multivariable modeling, characteristics of suicide decedents associated with a greater likelihood of firearm suicide were: male, black race, residing in the outer boroughs, and use of cannabis.

Conclusions:The proportion of suicides caused by firearms in NYC is low compared to other parts of the US; differential access to means of committing suicide and the differential importance of firearms in different racial and ethnic groups may contribute to this observation. Innovative, local population based interventions that target non-firearm related suicide may contribute to lower suicide mortality overall in urban areas.
The ICD-10 injury mortality diagnosis matrix
Authors: Fingerhut L A , Warner M
Published: February 2006

Objective:To standardize the presentation of the more than 1200 ICD-10 “S” and “T” codes from Chapter XIX by cross classifying the body region of injury by the nature of injury using the ICD-10 injury mortality diagnosis matrix. This paper explains the rationale for decisions made when developing the matrix and presents mortality data using the matrix.

Design:ICD-10 codes are organized by diagnosis groups and body regions of injury for the purpose of standardizing presentation. The categories can be collapsed to facilitate analysis at varying levels of detail. Findings from the United States 2002 injury mortality data are used as an example.

Main outcome measures:All injury diagnoses mentioned in deaths with an underlying cause of injury.

Results:There were a total of 247,195 injury diagnoses mentioned in the 161,269 deaths with an underlying cause of injury in 2002 in the United States. The matrix can be used to show that 30% of all injury diagnoses mentioned were to the head and neck region; 28% were system wide injuries, 17% were to the torso. Open wounds accounted for 17% of all injury diagnoses mentioned, and close to half of all open wounds were traumatic brain injuries. Twenty eight percent of injury diagnoses mentioned were unspecified as to their nature and 9.5% had no body region specified.

Conclusions:Multiple cause of death data are a rich but underused source of injury data often due to the complexity of the data and of the ICD classification system. Analytic techniques will need to be refined to accommodate deaths with multiple contributing injury diagnoses. The injury mortality diagnosis matrix will facilitate analysis as it is a useful tool for summarizing diagnosis data associated with injury deaths.
Validating self reported home safety practices in a culturally diverse non-inner city population
Authors: Hatfield P M , Staresinic A G , Sorkness C A , Peterson N M , Schirmer J , Katcher M L
Published: February 2006

Objective:To determine the validity of face to face, self reported responses to questions about the presence of safety devices and use of safety practices in the home aimed at preventing unintended injuries to preschool aged children.

Methods:The authors invited families with children enrolling in a medium sized Midwestern US community Head Start program to participate in a randomized study of home safety practices. Participation involved consenting parents (n = 452) completing an initial questionnaire during Head Start enrollment or in their home. Project staff conducted home inspections to confirm parental responses to 16 questions. Only inspections conducted within 34 days of questionnaire completion (n = 259) were included in the validation study. Parents were told that the home visit would assess the need for safety devices, but were not informed of the validation aspect of the study.

Results:Sensitivities were generally high for all 16 safety practices, whereas negative predictive value and specificity varied considerably. Positive predictive value was also high for most practices, and did not vary by ethnicity. Answers provided by parents in their home were different and more reliable than those provided by parents interviewed at school (p = 0.001).

Conclusions:Use of safety devices and practices by parents of preschool aged children reported in a face to face interview are generally reliable. Reliability increases if the interview is conducted in the home. Parents may also be more willing to report potential problems if they perceive they may receive corrective assistance.
Wheelchair related injuries treated in US emergency departments
Authors: Xiang H , Chany A-M , Smith G A
Published: February 2006

Objective:To characterize the trend of wheelchair related injuries over time, and describe the demographics and characteristics of wheelchair users’ injuries by age group.

Methods:Data from the National Electronic Injury Surveillance System (NEISS) were analyzed.

Results:In 2003, more than 100 000 wheelchair related injuries were treated in emergency departments in the US, double the number reported in 1991. Tips and falls accounted for 65–80% of injuries across all age groups of wheelchair users. The majority of children’s injuries occurred at locations outside of homes and institutions/hospitals in environments with stairs, ramps, and curbs (57.3%). In contrast, injuries among adult users were more likely to occur in homes, hospitals, and institutions (45–90%).

Conclusions:Wheelchair related injuries may have increased in the US during the past decade. Prevention efforts should address the interacting complex factors that influence risk of injury while using a wheelchair.
Emergency presentations by vulnerable road users: implications for injury prevention
Authors: Meuleners L B , Lee A H , Haworth C
Published: February 2006

Most emergency presentations by vulnerable road users were the result of collisions that did not involve a motor vehicle. Many injuries occurred off-road without police attendance. Hence, reliance on official police records would underestimate the magnitude and scope of these injuries. Suggestions to provide a safer road environment are given.
Violence in Jamaica: an analysis of homicides 1998–2002
Authors: Lemard G , Hemenway D
Published: February 2006

The aim of the study was to create a profile of Jamaican homicide victims and to describe the circumstances, motives, and the weapons used in homicide incidents. The authors read the police narratives for all Jamaican homicides 1998–2002 and coded them using a predetermined set of variables. Analyses were conducted to describe victim characteristics, motive, and weapon use. The majority of homicide victims were male (over 89%), and 15–44 years old (80%). The rate of homicide for males age 15–44 years was 121 per 100 000 compared with a rate of 12 per 100 000 for females in the same age group. The main motives for homicide were disputes (29%) and reprisals (30%). Gunshot wounds were the cause of death in 66% of all homicides. Guns were used primarily in reprisals, robbery, and drug/gang related homicides; in half of all dispute related homicides the perpetrator used a knife. Homicides in Jamaica are not primarily gang or robbery related. Rather, they are mainly caused by arguments or reprisals. Homicide has become a common feature of dispute resolution in Jamaica.
Treating vascular risk factors and maintaining vascular health: Is this the way towards successful cognitive ageing and preventing cognitive decline?
Authors: Alagiakrishnan K , McCracken P , Feldman H
Published: February 2006

Dementia is a progressive disorder that typically worsens with time and from which recovery is unlikely. The incidence of dementia increases exponentially with ageing and is an important public health challenge. There is now growing evidence for the role of vascular factors in Alzheimer's disease, mixed dementia (Alzheimer's disease with cerebrovascular disease), and of course vascular dementia. With the rising prevalence of vascular disease, there are increasing numbers of people who are identified to be at risk of cognitive impairment. By changing modifiable vascular risk factors, there is emerging evidence that it may be possible to prevent or delay the expression and progression of dementia.
Ageing and the brain
Authors: Peters R
Published: February 2006

Ageing causes changes to the brain size, vasculature, and cognition. The brain shrinks with increasing age and there are changes at all levels from molecules to morphology. Incidence of stroke, white matter lesions, and dementia also rise with age, as does level of memory impairment and there are changes in levels of neurotransmitters and hormones. Protective factors that reduce cardiovascular risk, namely regular exercise, a healthy diet, and low to moderate alcohol intake, seem to aid the ageing brain as does increased cognitive effort in the form of education or occupational attainment. A healthy life both physically and mentally may be the best defence against the changes of an ageing brain. Additional measures to prevent cardiovascular disease may also be important.
Parenteral nutrition: ethical and legal considerations
Authors: Sayers G M , Lloyd D A J , Gabe S M
Published: February 2006

Parenteral nutrition is an expensive therapeutic modality that is used to treat patients with intestinal failure. The benefit it offers in terms of life prolongation needs to be weighed against its risks and burdens. Through the use of descriptive clinical vignettes, this article illustrates the ethical and legal principles that underpin decisions to administer and, more importantly, to withhold or withdraw parenteral nutrition.
Medical and surgical management of priapism
Authors: Cherian J , Rao A R , Thwaini A , Kapasi F , Shergill I S , Samman R
Published: February 2006

Priapism is a pathological condition of penile erection that persists beyond, or is unrelated to, sexual stimulation. Pathologically and clinically, two subtypes are seen—the high flow (non-ischaemic) variety and the low flow (ischaemic) priapism. The low flow type is more dangerous, as these patients are susceptible to greater complications and the long term recovery of erectile function is dependent on prompt and urgent intervention. Many of the causes of priapism are medical, including pharmacological agents, and as such, priapism should be considered as a medical and surgical emergency.
Cardiovascular complications of severe acute respiratory syndrome
Authors: Yu C-M , Wong R S-M , Wu E B , Kong S-L , Wong J , Yip G W-K , Soo Y O Y , Chiu M L S , Chan Y-S , Hui D , Lee N , Wu A , Leung C-B , Sung J J-Y
Published: February 2006

Background and Aims

Severe acute respiratory syndrome (SARS) is a virulent viral infection that affects a number of organs and systems. This study examined if SARS may result in cardiovascular complications.

Methods and Results

121 patients (37.5 (SD13.2) years, 36% male) diagnosed to have SARS were assessed continuously for blood pressure, pulse, and temperature during their stay in hopsital. Hypotension occurred in 61 (50.4%) patients in hospital, and was found in 28.1%, 21.5%, and 14.8% of patients during the first, second, and third week, respectively. Only one patient who had transient echocardiographic evidence of impaired left ventricular systolic function required temporary inotropic support. Tachycardia was present in 87 (71.9%) patients, and was found in 62.8%, 45.4%, and 35.5% of patients from the first to third week. It occurred independent of hypotension, and could not be explained by the presence of fever. Tachycardia was also present in 38.8% of patients at follow up. Bradycardia only occurred in 18 (14.9%) patients as a transient event. Reversible cardiomegaly was reported in 13 (10.7%) patients, but without clinical evidence of heart failure. Transient atrial fibrillation was present in one patient. Corticosteroid therapy was weakly associated with tachycardia during the second (χ2 = 3.99, p = 0.046) and third week (χ2 = 6.53, p = 0.01), although it could not explain tachycardia during follow up.

Conclusions

In patients with SARS, cardiovascular complications including hypotension and tachycardia were common but usually self limiting. Bradycardia and cardiomegaly were less common, while cardiac arrhythmia was rare. However, only tachycardia persisted even when corticosteroid therapy was withdrawn.
Uroscopic rainbow: modern matula medicine
Authors: Foot C L , Fraser J F
Published: February 2006

Visual inspection of a patient's urine has long been used by physicians, with colour recognised as having important clinical implications. In this review the authors will revisit this ancient pastime with relevance to contemporary medical practice.
Portrayal of negative qualities in a doctor as a potential teaching tool in medical ethics and humanism:Journey to the End of Nightby Louis-Ferdinand Céline
Authors: Wolf G
Published: February 2006

Fictional stories about physicians and patients are increasingly used as a powerful teaching resource for medical students. Very often, but not exclusively, stories of physicians as positive role models are selected to teach students virtues and ethical values. Negative role models are rarely used and if so, physicians are rather described as medical quacks in such fiction then exhibiting primarily a corrupted character. I suggest that a fictional story that presents exclusively a negative role model of a physician could also be a valuable, admittedly difficult, teaching resource to demonstrate the consequences of absolute loss of ethical standards and virtues in physicians. A not widely known example of this genre is Louis-Ferdinand Céline's (1894–1961) novel Voyage au bout de la nuit (Journey to the End of the Night), published in 1932. Having a strong autobiographical background, the novel described the adventures of the medicine student, Ferdinand Bardamu, during the first world war, in the African colonies as a trader, in the United States of America as factory worker, and later after finishing his education, as a doctor for the poor. Unfortunately, Dr Bardamu develops an unprofessional, even criminal behaviour, and may serve as a negative role model for the virtues of physicians. This article will familiarise the reader with the novel and its physician author.
Analysis of predictors of success in the MRCP (UK) PACES examination in candidates attending a revision course
Authors: Bessant R , Bessant D , Chesser A , Coakley G
Published: February 2006

Objective

To determine factors that predict success of candidates taking a revision course in preparation for the MRCP (UK) PACES (practical assessment of clinical examination skills) examination.

Design

A questionnaire survey of candidates attending a PACES revision course. Results were correlated with subsequent pass lists published by the Colleges of Physicians

Setting and subjects

Candidates attending courses in June and October 2002. In total, 523 candidates completed questionnaires, evenly balanced between UK and overseas graduates.

Results

Of 483 candidates who took the examination immediately after the course, 219 (45.3%) passed. UK graduates were more likely to pass (67.0%) than overseas graduates (26.2%) (p = 0.003, odds ratio 5.72). For UK graduates, pass rates were higher for white candidates (73%) than for ethnic minorities (56%) (p = 0.012, OR 2.15) and for those who passed at the first attempt in the MRCP (UK) part 2 written paper (p = 0.003, OR 2.90). For overseas graduates, those who had been qualified for less than eight years were more likely to pass (p = 0.001, OR 2.78). More overseas (45.7%) than UK (30.8%) graduates were confident that they would pass, but confidence did not predict success.

Conclusion

Among candidates taking a revision course, UK graduates are more likely to pass the PACES examination than non-UK graduates. Ethnic minority UK graduates seem to have a significantly poorer success rate, although this requires confirmation in an independent sample. If confirmed, these differences merit further investigation to assess whether they reflect genuine differences in ability.
Luminal leptin activates mucin-secreting goblet cells in the large bowel
Authors: Plaisancie Pascale , Ducroc Robert , Homsi Mahmoud El , Tsocas Annick , Guilmeau Sandra , Zoghbi Sandra , Thibaudeau Olivier , Bado Andre
Published: February 2006

Leptin has been suggested to be involved in tissue injury and/or mucosal defence mechanisms. Here, we studied the effects of leptin on colonic mucus secretion and rat mucin 2 (rMuc2) expression. Wistar rats and ob/ ob mice were used. Secretion of mucus was followed in vivo in the rat perfused colon model. Mucus secretion was quantified by ELISA, and rMuc2 mRNA levels were quantified by real-time RT PCR. The effects of leptin alone or in association with protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) inhibitors on mucin secreted by human mucus-secreting HT29-MTX cells were determined. Leptin was detected in the rat colonic lumen at substantial levels. Luminal perfusion of leptin stimulates mucus-secreting goblet cells in a dose-dependent manner in vivo in the rat. Leptin (10 nmol/l) increased mucus secretion by a factor of 3.5 and doubled rMuc2 mRNA levels in the colonic mucosa. There was no damage to mucosa 24 h after leptin, but the number of stained mucus cells significantly increased. Leptin-deficient ob/ ob mice have abnormally dense mucus-filled goblet cells. In human colonic goblet-like HT29-MTX cells expressing leptin receptors, leptin increased mucin secretion by activating PKC- and PI3K-dependent pathways. This is the first demonstration that leptin, acting from the luminal side, controls the function of mucus-secreting goblet cells. Because the gel layer formed by mucus at the surface of the intestinal epithelium has a barrier function, our data may be relevant physiologically in defence mechanisms of the gastrointestinal tract.
Comparison of rectoanal axial forces in health and functional defecatory disorders
Authors: Bharucha Adil E. , Croak Andrew J. , Gebhart John B. , Berglund Lawrence J. , Seide Barbara M. , Zinsmeister Alan R. , An Kai-Nan
Published: February 2006

Anal manometry measures circumferential pressures but not axial forces that are responsible for defecation and contribute to fecal continence. Our aims were to investigate these mechanisms by measuring axial rectoanal forces with an intrarectal sphere or a latex balloon fixed at 8, 6, or 4 cm from the anal verge and connected to axial force and displacement transducers. Rectoanal forces and rectal pressures within a latex balloon were measured at baseline (i.e., at rest) and during maneuvers (i.e., squeeze, simulated evacuation, and a Valsalva maneuver) in 12 asymptomatic women and 12 women with symptoms of difficult defecation. Anal resting and squeeze pressures were also assessed by manometry and were similar in control patients and experimental patients. At rest, axial rectoanal forces were directed inward and increased as the device approached the anal verge. Control patients augmented this inward force when they squeezed and exerted an outward force during simulated expulsion and a Valsalva maneuver. The force change during maneuvers was also affected by device location and was highest at 4 cm from the verge. In experimental patients, the force at rest and the change in force during all maneuvers was lower than in control patients. The rectal pressure during a Valsalva maneuver was also lower in experimental patients than in control patients, suggestive of impaired propulsion. In conclusion, a subset of women with defecatory symptoms had weaker axial forces not only during expulsion but also during a Valsalva maneuver and when they squeezed (i.e., contracted) their pelvic floor muscles, suggestive of generalized pelvic floor weakness.
Isolation, functional characterization, and transcriptome of Mastomys ileal enterochromaffin cells
Authors: Kidd M. , Modlin I. M. , Eick G. N. , Champaneria M. C.
Published: February 2006

Although the enterochromaffin (EC) cell is one of the primary neuroendocrine regulatory cells of the small intestine, the lack of a purified cell system has precluded characterization of the cell and limited precise physiological evaluation. We developed methodology to obtain a pure population of Mastomys ileal EC cells, evaluated their functional regulation, and defined the transcriptome. Mastomys ilea were everted, end ligated, pronase-collagenase digested, and Nycodenz gradient centrifuged, and EC cells were collected by fluorescence-activated cell sorting (FACS) of acridine orange-labeled cells. Enrichment was confirmed by immunostaining of tryptophan hydroxylase and chromogranin A, specific EC cell markers, serotonin content, EC cell marker gene expression, and electron microscopy. Pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin, and gastrin receptor expression was determined by real-time RT-PCR. Live post-FACS-sorted cells were cultured, and the effects of forskolin, isoproterenol, acetylcholine, GABAA, PACAP-38, and gastrin on serotonin secretion were measured by ELISA. GeneChip Affymetrix profiling of FACS-sorted cells was undertaken to obtain the EC cell transcriptome. FACS produced a >70-fold enrichment of EC cells with a serotonin content of 240 ± 22 ng/mg protein. Preparations were 99 ± 0.7% pure by immunostaining for tryptophan hydroxylase. Vasoactive intestinal peptide/PACAP receptor 1 (VPAC1) and somatostatin receptor 2 were present, whereas PACAP receptor 1 (PAC1) and CCK2 receptors were undetectable. Forskolin, isoproterenol, and PACAP-38 stimulated serotonin secretion at EC50 values of 5 × 10−10, 4.5 × 10−10, and 1.2 × 10−9 M, respectively. Isoproterenol stimulated cAMP levels by ∼3.5 ± 0.62-fold vs. unstimulated cells (EC50 of ∼10−9 M). Octreotide, acetylcholine, and GABAA inhibited serotonin secretion with IC50 values of 3 × 10−11, 3 × 10−10, and 2.9 × 10−10 M, respectively. Gastrin had no effect on serotonin secretion. The naive EC cell transcriptome revealed highly expressed EC cell marker genes, the absence of marker genes for other small intestinal cell types, and a receptor profile that included cholinergic, adrenergic, dopaminergic, serotoninergic, GABAergic, and prostaglandin receptors. We were able to isolate homogeneous preparations (>99%) of live ileal EC cells and demonstrated regulation of serotonin secretion as well as established the normal EC cell transcriptome. Application of this methodology to normal and diseased human ileum will facilitate the elucidation of the pathophysiology of EC cells.
Age-specific pulmonary cytochrome P-450 3A1 expression in postnatal and adult rats
Authors: Day Kimberly C. , Plopper Charles G. , Fanucchi Michelle V.
Published: February 2006

A major cause of death and illness in children under the age of five, most living in polluted cities, is respiratory disease. Previous studies have shown that neonatal animals are more susceptible to bioactivated pulmonary cytotoxicants than adults, despite lower expression of the pulmonary cytochrome P-450s (CYP450s) thought to be involved in bioactivation. One CYP450 that is well documented in the bioactivation of many drugs and environmental toxicants in adult lung, but whose expression has not been evaluated during postnatal pulmonary development, is CYP450 3A (CYP3A). We compared age-specific expression of CYP3A1 in 7-day-old and adult male Sprague-Dawley rats. Unlike those shown for previously studied pulmonary CYP450s, expression levels for CYP3A1 mRNA in differentiating airway cells of postnatal rats are the same as in fully differentiated airway cells of adults. CYP3A1 protein expression (28%) and enzymatic activity (23%) were lower in postnatal airways compared with adults. Although other CYP450 immunoreactive proteins are primarily expressed in nonciliated cells, immunoreactive CYP3A1 protein was expressed in both ciliated and nonciliated cells in postnatal and adult rat proximal airways. CYP3A1 protein is detected diffusely throughout ciliated and nonciliated cells in 7-day-old rats, whereas it is only detected in the apex of these cells in adult rats. This study demonstrates that the lungs of postnatal rats have detectable levels of CYP3A1 and that CYP3A1 mRNA expression appears not to be age dependent, whereas steady-state CYP3A1 protein levels and enzyme activity show an age-dependent pattern.
Reduced stress- and cold-induced increase in energy expenditure in interleukin-6-deficient mice
Authors: Wernstedt Ingrid , Edgley Amanda , Berndtsson Anna , Fäldt Jenny , Bergström Göran , Wallenius Ville , Jansson John-Olov
Published: February 2006

Interleukin-6 (IL-6) deficient (-/-) mice develop mature onset obesity. Pharmacological studies have shown that IL-6 has direct lipolytic effects and when administered centrally increases sympathetic outflow. However, the metabolic functions of endogenous IL-6 are not fully elucidated. We aimed to investigate the effect of IL-6 deficiency with respect to cold exposure and cage-switch stress, that is, situations that normally increase sympathetic outflow. Energy metabolism, core temperature, heart rate, and activity were investigated in young preobese IL-6−/− mice by indirect calorimetry together with telemetry. Baseline measurements and the effect of cage-switch stress were investigated at thermoneutrality (30°C) and at room temperature (20°C). The effect of cold exposure was investigated at 4°C. At 30°C, the basal core temperature was 0.6 ± 0.24°C lower in IL-6−/− compared with wild-type mice, whereas the oxygen consumption did not differ significantly. The respiratory exchange ratio at 20°C was significantly higher and the calculated fat utilization rate was lower in IL-6−/− mice. In response to cage-switch stress, the increase in oxygen consumption at both 30 and 20°C was lower in IL-6−/− than in wild-type mice. The increase in heart rate was lower in IL-6−/− mice at 30°C. At 4°C, both the oxygen consumption and core temperature were lower in IL-6−/− compared with wild-type mice, suggesting a lower cold-induced thermogenesis in IL-6−/− mice. The present results indicate that endogenous IL-6 is of importance for stress- and cold-induced energy expenditure in mice.
Insulin and growth hormone stimulate somatostatin receptor (SSTR) expression by inducing transcription of SSTR mRNAs and by upregulating cell surface SSTRs
Authors: Nelson Laura E. , Sheridan Mark A.
Published: February 2006

This study examined the effects of insulin (INS) and growth hormone (GH) on mRNA and functional expression of somatostatin receptors (SSTRs). Rainbow trout liver was used as a model system to evaluate the direct effects of INS and GH on mRNA expression of three SSTR subtypes characterized previously from this species: SSTR1A, SSTR1B, and SSTR2. INS and GH directly stimulated steady-state levels of all SSTR mRNAs in a concentration- and time-dependent manner; however, the pattern of expression was hormone and SSTR subtype specific. INS stimulated SSTR2 expression to a greater extent than SSTR1A or SSTR1B expression, whereas GH stimulated SSTR2 and SSTR1B expression to a similar extent, with SSTR2 and SSTR1B expression being more responsive to GH than SSTR1A. Whether INS- or GH-stimulated SSTR expression resulted from altered rates of transcription and/or changes in mRNA stability also was investigated. Formation of nascent SSTR transcripts in nuclei isolated from rainbow trout hepatocytes was significantly stimulated by INS and GH. Neither INS nor GH, however, affected the stability of SSTR mRNAs. Functional expression of SSTRs was studied in Chinese hamster ovary (CHO-K1) cells stably transfected with SSTR1A or SSTR1B. Surface expression of functional SSTRs was stimulated by INS and GH. These findings indicate that INS and GH stimulate SSTR expression by regulating transcription of SSTR mRNAs and by increasing functional SSTRs on the cell surface, and they suggest that regulation of SSTRs may be important for the coordination of growth, development, and metabolism of vertebrates.
Peripheral metabolic responses to prolonged weight reduction that promote rapid, efficient regain in obesity-prone rats
Authors: MacLean Paul S. , Higgins Janine A. , Jackman Matthew R. , Johnson Ginger C. , Fleming-Elder Brooke K. , Wyatt Holly R. , Melanson Edward L. , Hill James O.
Published: February 2006

Weight regain after weight loss is the most significant impediment to long-term weight reduction. We have developed a rodent paradigm that models the process of regain after weight loss, and we have employed both prospective and cross-sectional analyses to characterize the compensatory adaptations to weight reduction that may contribute to the propensity to regain lost weight. Obese rats were fed an energy-restricted (50–60% kcal) low-fat diet that reduced body weight by 14%. This reduced weight was maintained for up to 16 wk with limited provisions of the low-fat diet. Intake restriction was then removed, and the rats were followed for 56 days as they relapsed to the obese state. Prolonged weight reduction was accompanied by 1) a persistent energy gap resulting from an increased drive to eat and a reduced expenditure of energy, 2) a higher caloric efficiency of regain that may be linked with suppressed lipid utilization early in the relapse process, 3) preferential lipid accumulation in adipose tissue accompanied by adipocyte hyperplasia, and 4) humoral adiposity signals that underestimate the level of peripheral adiposity and likely influence the neural pathways controlling energy balance. Taken together, long-term weight reduction in this rodent paradigm is accompanied by a number of interrelated compensatory adjustments in the periphery that work together to promote rapid and efficient weight regain. These metabolic adjustments to weight reduction are discussed in the context of a homeostatic feedback system that controls body weight.
Inhibition of caspase-1 in rat brain reduces spontaneous nonrapid eye movement sleep and nonrapid eye movement sleep enhancement induced by lipopolysaccharide
Authors: Imeri Luca , Bianchi Susanna , Opp Mark R.
Published: February 2006

Evidence suggests that IL-1β is involved in promoting physiological nonrapid eye movement (NREM) sleep. IL-1β has also been proposed to mediate NREM sleep enhancement induced by bacteria or their components. Mature and biologically active IL-1β is cleaved from an inactive precursor by a cysteinyl aspartate-specific protease (caspase)-1. This study aimed to test the hypothesis that inhibition in brain of the cleavage of biologically active IL-1β will reduce in rats both spontaneous NREM sleep and NREM sleep enhancement induced by the peripheral administration of components of the bacterial cell wall. To test this hypothesis, rats were intracerebroventricularly administered the caspase-1 inhibitor Ac-Tyr-Val-Ala-Asp chloromethyl ketone (YVAD; 3, 30, 300, and 1,500 ng) or were pretreated intracerebroventricularly with YVAD (300 ng) and then intraperitoneally injected with the gram-negative bacterial cell wall component LPS (250 μg/kg). Subsequent sleep-wake behavior was determined by standard polygraphic recordings. YVAD administration at the beginning of the light phase of the light-dark cycle significantly reduced time spontaneously spent in NREM sleep during the first 12 postinjection hours. YVAD pretreatment also completely prevented NREM sleep enhancement induced by peripheral LPS administration at the beginning of the dark phase. These results, in agreement with previous evidence, support the involvement of brain IL-1β in physiological promotion of NREM sleep and in mediating NREM sleep enhancement induced by peripheral immune challenge.
Early postnatal chronic intermittent hypoxia modifies hypoxic respiratory responses and long-term phrenic facilitation in adult rats
Authors: Reeves Stephen R. , Mitchell Gordon S. , Gozal David
Published: February 2006

Acute isocapnic intermittent hypoxia elicits time-dependent, serotonin-dependent enhancement of phrenic motor output in anesthetized rats (phrenic long-term facilitation, pLTF). In adult rats, pLTF is enhanced by chronic intermittent hypoxia (CIH). To test the hypothesis that early postnatal CIH induces persistent modifications of ventilation and pLTF, we exposed male Sprague-Dawley rat pups on their first day of life to a CIH profile consisting of alternating room air and 10% oxygen every 90 s for 30 days during daylight hours (RAIH) or to comparable exposures consisting of room air throughout (RARA). One month after cessation of CIH, respiratory responses were recorded using whole body plethysmography, and integrated phrenic nerve activity was recorded in urethane-anesthetized, vagotomized, paralyzed, and ventilated rats at baseline and after exposures to three 5-min hypoxic episodes [inspired O2 fraction (FiO2) = 0.11] separated by 5 min of hyperoxia (FiO2 = 0.5). RAIH rats displayed greater normoxic ventilation and also increased burst frequency compared with RARA rats ( P < 0.01). Ventilatory responses to hypoxia and short-term phrenic responses during acute hypoxic challenges were reduced in RAIH rats ( P < 0.01). Although pLTF was present in both RAIH and RARA rats, it was diminished in RAIH rats (minute activity: 74 ± 2% in RARA vs. 55 ± 5% in RAIH at 60 min; P < 0.01). Thus we conclude that early postnatal CIH modifies normoxic and hypoxic ventilatory and phrenic responses that persist at 1 mo after cessation of CIH (i.e., metaplasticity) and markedly differ from previously reported increased neural plasticity changes induced by CIH in adult rats.
Water ingestion by rats fed a high-salt diet may be mediated, in part, by visceral osmoreceptors
Authors: Manesh Reza , Hoffmann Myriam L. , Stricker Edward M.
Published: February 2006

After surgical removal of all salivary secretions (“desalivation”), rats increase their consumption of water while eating dry laboratory chow. In the present experiments, desalivated rats drank even more water while they ate “powdered” high-salt food (i.e., <15-mg food particles). The Na+ concentration of systemic plasma in these animals was not elevated during or immediately after the meal, which suggests that cerebral osmoreceptors were not involved in mediating the increased water intake. A presystemic osmoregulatory signal likely stimulated thirst because the Na+ and water contents of the gastric chyme computed to a solution ∼150 mM NaCl. In contrast, desalivated rats drank much smaller volumes of water while eating “pulverized” high-salt food (i.e., 60–140-mg food particles), and the fluid mixture in the gastric chyme computed to ∼280 mM NaCl solution. These and other findings suggest that the NaCl ingested in the powdered high-salt diet was dissolved in the gastric fluid and that duodenal osmoreceptors (or Na+-receptors) detected when the concentration of fluid leaving the stomach was elevated after each feeding bout, and promptly stimulated thirst, whereupon rats drank water until the gastric fluid was diluted back to isotonicity. However, when rats ate the pulverized high-salt diet, much of the NaCl ingested may have been embedded in the gastric chyme and therefore was not accessible to visceral osmoreceptors once it emptied from the stomach. Consistent with that hypothesis, fluid intakes were increased considerably when desalivated rats drank 0.10 M NaCl instead of water while eating either powdered or pulverized high-salt food.
Claudins at the gate: determinants of renal epithelial tight junction paracellular permeability
Authors: Balkovetz Daniel F.
Published: February 2006

The epithelial tight junction (TJ) is responsible for the control of paracellular transport between epithelial cells (gate function) and the maintenance of apical/basolateral polarity by preventing the diffusion of membrane lipids and/or proteins from one surface domain to another (fence function). Renal tubule epithelia in the mammalian nephron have TJs that determine paracellular transport characteristics. Paracellular transport across renal tubular epithelial TJs (gate function) varies in different segments of the nephron. A large family of recently identified TJ-associated transmembrane proteins named claudins appear to determine the paracellular permeability properties of the TJ. A combination of inherited human diseases, renal epithelial cell culture models, and nephron expression patterns of claudins is providing important clues about how claudin molecules determine the TJ gate function of renal epithelia in different segments of the nephron.
Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia
Authors: Hsu Andrew R. , Barnholt Kimberly E. , Grundmann Nicolas K. , Lin Joseph H. , McCallum Stewart W. , Friedlander Anne L.
Published: February 2006

Sildenafil causes pulmonary vasodilation, thus potentially reducing impairments of hypoxia-induced pulmonary hypertension on exercise performance at altitude. The purpose of this study was to determine the effects of sildenafil during normoxic and hypoxic exercise. We hypothesized that 1) sildenafil would have no significant effects on normoxic exercise, and 2) sildenafil would improve cardiac output, arterial oxygen saturation (SaO2), and performance during hypoxic exercise. Ten trained men performed one practice and three experimental trials at sea level (SL) and simulated high altitude (HA) of 3,874 m. Each cycling test consisted of a set-work-rate portion (55% work capacity: 1 h SL, 30 min HA) followed immediately by a time trial (10 km SL, 6 km HA). Double-blinded capsules (placebo, 50, or 100 mg) were taken 1 h before exercise in a randomly counterbalanced order. For HA, subjects also began breathing hypoxic gas (12.8% oxygen) 1 h before exercise. At SL, sildenafil had no effects on any cardiovascular or performance measures. At HA, sildenafil increased stroke volume (measured by impedance cardiography), cardiac output, and SaO2during set-work-rate exercise. Sildenafil lowered 6-km time-trial time by 15% ( P < 0.05). SaO2was also higher during the time trial ( P < 0.05) in response to sildenafil, despite higher work rates. Post hoc analyses revealed two subject groups, sildenafil responders and nonresponders, who improved time-trial performance by 39% ( P < 0.05) and 1.0%, respectively. No dose-response effects were observed. During cycling exercise in acute hypoxia, sildenafil can greatly improve cardiovascular function, SaO2, and performance for certain individuals.
Prostaglandin involvement in lung C-fiber activation by substance P in guinea pigs
Authors: Bergren Dale R.
Published: February 2006

Airway hyperresponsiveness is a cardinal feature of asthma. Lung C-fiber activation induces central and local defense reflexes that may contribute to airway hyperresponsiveness. Initial studies show that substance P (SP) activates C fibers even though it is produced and released by these same C fibers. SP may induce release of other endogenous mediators. Bradykinin (BK) is an endogenous mediator that activates C fibers. The hypothesis was tested that SP activates C fibers via BK release. Guinea pigs were anesthetized, and C-fiber activity (FA), pulmonary insufflation pressure (PIP), heart rate, and arterial blood pressure were monitored before and after intravenous injection of capsaicin (Cap), SP, and BK. Identical agonist challenges were repeated after infusion of an antagonist cocktail of des-Arg9-[Leu8]-BK (10−3M, B1antagonist), and HOE-140 (10−4M, B2antagonist). After antagonist administration, BK increased neither PIP nor FA. Increases in neither PIP nor FA were attenuated after Cap or SP challenge. In a second series of experiments, Cap and SP were injected before and after infusion of indomethacin (1 mg/kg iv) to determine whether either agent activates C fibers through release of arachidonic acid metabolites. Indomethacin administration decreased the effect of SP challenge on FA but not PIP. The effect of Cap on FA or PIP was not altered by indomethacin. In subsequent experiments, C fibers were activated by prostaglandin E2and F2α. Therefore, exogenously applied SP stimulates an indomethacin-sensitive pathway leading to C-fiber activation.
Snoring-related energy transmission to the carotid artery in rabbits
Authors: Amatoury Jason , Howitt Lauren , Wheatley John R. , Avolio Albert P. , Amis Terence C.
Published: February 2006

Epidemiological studies link habitual snoring and stroke, but mechanisms involved are poorly understood. One previously advanced hypothesis is that transmitted snoring vibration energy may promote carotid atheromatous plaque formation or rupture. To test whether vibration energy is present in carotid artery walls during snoring we developed an animal model in which we examined induced snoring (IS)-associated tissue energy levels. In six male, supine, anesthetized, spontaneously breathing New Zealand White rabbits, we surgically inserted pressure transducer-tipped catheters (Millar) to monitor tissue pressure at the carotid artery bifurcation (PCT) and within the carotid sinus lumen (PCS; artery ligated). Snoring was induced via external compression (sandbag) over the pharyngeal region. Data were analyzed using power spectral analysis for frequency bands above and below 50 Hz. For frequencies below 50 Hz, PCTenergy was 2.2 (1.1–12.3) cmH2O2[median (interquartile range)] during tidal breathing (TB) increasing to 39.0 (2.5–95.0) cmH2O2during IS ( P = 0.05, Wilcoxon's signed-rank test). For frequencies >50 Hz, PCTenergy increased from 9.2 (8.3–10.4) × 10−4cmH2O2during TB to 172.0 (118.0–569.0) × 10−4cmH2O2during IS ( P = 0.03). Concurrently, PCSenergy was 13.4 (8.5–18.0) × 10−4cmH2O2during TB and 151.0 (78.2–278.8) × 10−4cmH2O2during IS ( P < 0.03). The PCSenergy was greater than PCTenergy for the 100–275 Hz bandwidth. In conclusion, during IS there is increased energy around and within the carotid artery, including lower frequency amplification for PCS. These findings may have implications for carotid atherogenesis and/or plaque rupture.
Arteriolar smooth muscle Ca2+dynamics during blood flow control in hamster cheek pouch
Authors: Brekke Johan Fredrik , Jackson William F. , Segal Steven S.
Published: February 2006

Intracellular calcium concentration ([Ca2+]i) governs the contractile status of arteriolar smooth muscle cells (SMC). Although studied in vitro, little is known of SMC [Ca2+]idynamics during the local control of blood flow. We tested the hypothesis that the rise and fall of SMC [Ca2+]iunderlies arteriolar constriction and dilation in vivo. Aparenchymal segments of second-order arterioles (diameter 35 ± 2 μm) were prepared in the superfused cheek pouch of anesthetized hamsters ( n = 18) and perifused with the ratiometric dye fura PE-3 (AM) to load SMC (1 μM, 20 min). Resting SMC [Ca2+]iwas 406 ± 37 nM. Elevating superfusate O2from 0 to 21% produced constriction (11 ± 2 μm) that was unaffected by dye loading; [Ca2+]iincreased by 108 ± 53 nM ( n = 6, P < 0.05). Cycling of [Ca2+]iduring vasomotion (amplitude, 150 ± 53 nM; n = 4) preceded corresponding diameter changes (7 ± 1 μm) by ∼2 s. Microiontophoresis (1 μm pipette tip; 1 μA, 1 s) of phenylephrine (PE) transiently increased [Ca2+]iby 479 ± 64 nM ( n = 8, P < 0.05) with constriction (26 ± 3 μm). Flushing blood from the lumen with saline increased fluorescence at 510 nm by ∼45% during excitation at both 340 and 380 nm with no difference in resting [Ca2+]i, diameter or respective responses to PE ( n = 7). Acetylcholine microiontophoresis (1 μA, 1 s) transiently reduced resting SMC [Ca2+]iby 131 ± 21 nM ( n = 6, P < 0.05) with vasodilation (17 ± 1 μm). Superfusion of sodium nitroprusside (10 μM) transiently reduced SMC [Ca2+]iby 124 ± 18 nM ( n = 6, P < 0.05), whereas dilation (23 ± 5 μm) was sustained. Resolution of arteriolar SMC [Ca2+]iin vivo discriminates key signaling events that govern the local control of tissue blood flow.
VEGF as a Therapeutic Target in Cancer
Authors: Ferrara Napoleone
Published: February 2006

Tumors require nutrients and oxygen in order to grow, and new blood vessels, formed by the process of angiogenesis, provide these substrates. The key mediator of angiogenesis is vascular endothelial growth factor (VEGF), which is induced by many characteristics of tumors, most importantly hypoxia. Therefore, VEGF is an appealing target for anticancer therapeutics. In addition, VEGF is easy to access as it circulates in the blood and acts directly on endothelial cells. VEGF-mediated angiogenesis is rare in adult humans (except wound healing and female reproductive cycling), and so targeting the molecule should not affect other physiological processes. Tumor blood vessels, formed under the influence of VEGF, are disorganized, tortuous and leaky with high interstitial pressure, reducing access for chemotherapies. Inhibiting VEGF would reduce the vessel abnormality and increase the permeability of the tumor to chemotherapies. Several approaches to targeting VEGF have been investigated. The most common strategies have been receptor-targeted molecules and VEGF-targeting molecules. The disadvantage of receptor-targeted approaches is that the VEGF receptors also bind different members of the VEGF super-family and affect systems other than angiogenesis. The best-studied and most advanced approach to VEGF inhibition is the humanized monoclonal antibody bevacizumab (Avastin®), which is the only anti-angiogenic agent approved for treatment of cancer.