bluuebunny/crossref_metadata_2025 huggingface dataset:
Helping Medicare Patients Benefit From the New Medicare Drug Benefit: An Overview With Practice Tips
Authors: Donohue Julie , Hanlon Joseph T.
Published: January 2007

The new Medicare drug benefit (Part D) will expand drug coverage to the millions of Medicare beneficiaries who currently lack insurance protection against the costs of prescription drugs. This dramatic expansion of benefits could increase medication treatment for many chronic health conditions, but the impact of Part D on the affordability of prescription drugs depends on a series of choices beneficiaries must make including whether to sign up for the voluntary benefit and which of several drug plans to choose. Private prescription drug plans administering the benefit will vary in terms of the cost sharing, premiums, and formulary design. Providers can play an important role in providing patients with the resources necessary to make good choices regarding drug coverage. Medicare will also provide reimbursement for medication therapy management. The transition of Medicare beneficiaries to Part D drug plans provides an important opportunity for providers to review and possibly make changes to their elderly patients' drug regimens to maximize effectiveness while minimizing costs to patients.
Health‐Related Quality of Life Following Percutaneous Coronary Intervention: The Impact of Age on Outcome at 1 Year
Authors: Moore Roger , Pedel Sangeev , Lowe Robert , Perry Raphael
Published: January 2007

This study was performed to assess the possibility that patient age may independently affect improvements in health‐related quality of life following percutaneous coronary intervention. One hundred five patients undergoing elective percutaneous coronary intervention at a single tertiary referral center between January 10, 2001 and January 6, 2002 were enrolled and prospectively evaluated. Health‐related quality of life was assessed before and 1 year following percutaneous coronary intervention using Short Form‐12 and the Seattle Angina Questionnaire. For the purpose of analysis, patients were divided according to age (younger than 60, 60–70, and older than 70 years). One hundred patients (95%) completed both questionnaires. Baseline characteristics among the age groups were similar in terms of gender, cardiac risk factors, and procedural details. All health‐related quality‐of‐life indices demonstrated improvements with at least four variables in each group achieving a clinically significant increase (>20%). At least eight modalities in each group achieved statistical significance (p=0.01). With the exception of physical functioning, the improvements in health‐related quality of life were not significantly different among age groups.
Influence of Age and Coronary Artery Disease on Homocysteine Levels in the Young Old Compared With the Old Old and the Oldest Old
Authors: Gravina Claudia F. , Batlouni Michel , Sarteschi Camila , Sousa Amanda G.M.R. , Eduardo J. , Sousa M.R. , Piegas Leopoldo
Published: January 2007

A total of 172 elderly individuals, divided into case and control groups based on the diagnosis of coronary artery disease, underwent coronary angiography to investigate the influence of age and coronary artery disease on homocysteine levels. The subjects were divided into three age ranges: 65–74 years, 75–79 years, and 80 years and older. Continuous homocysteinemia was associated with a risk ratio for coronary artery disease of 1.07 for each μmol/L increase in homocysteine level. Hyperhomocysteinemia (values above 14 μmol/L) constituted an independent risk factor for coronary artery disease, with a risk ratio of 2.03. There was a progression of homocysteine levels between the young old and the oldest old only among the case group elderly. There was no difference among the control group elderly. There were no significant differences in vitamin levels. The rise in homocysteine levels from the young old to the oldest old may be considered not a normal pattern, but rather a pattern associated with coronary artery disease.
Prevalence of Interatrial Block in the Program of All‐Inclusive Care for the Elderly (PACE)
Authors: Ariyarajah Vignendra , Puri Puneet , Kranis Mark , Wilner David A. , Spodick David H.
Published: January 2007

Interatrial block (IAB) (P wave ≥110 milliseconds) is a potent correlate of atrial tachyarrhythmias, left atrial electromechanical dysfunction, and embolism. IAB has been demonstrated to be highly prevalent in the general hospital population, but no investigation has addressed this in the elderly community outside the hospital. We appraised the prevalence of IAB in a service of the Program of All‐Inclusive Care for the Elderly (PACE), the Elder Service Plan (ESP). Of the 202 ESP members in Worcester, MA, 167 (ages 61–103 years; female 81.4%) who had current 12‐lead electrocardiograms were evaluated for IAB, and an age‐based comparison was made between those with and without IAB. Of those patients with current electrocardiograms, 148 (88.6%) showed sinus rhythm and 72 (48.6%) depicted IAB: 20% in patients aged 60–69 years, 39.5% aged 70–79 years, 56.8% aged 80–89 years, and 50% in those 90 years and older. Given its sequelae of anatomic and pathophysiologic consequences, prompt recognition of IAB in a high‐risk group such as that in the PACE community (48.6% prevalence) is important, especially for anticipation of atrial fibrillation and possible embolism.
Pulse Pressure and Vascular Risk in the Elderly: Associations and Clinical Implications
Authors: Swaminathan Rajesh V. , Alexander Karen P.
Published: January 2007

Pulse pressure provides information beyond systolic and diastolic blood pressures, from which it is calculated. The majority of individuals older than 70 years have a widened pulse pressure resulting from age‐related stiffening of the central elastic arteries and systolic hypertension. A widened pulse pressure is associated with cardiovascular risk factors such as diabetes, hypertension, and smoking. It also predicts a higher risk of subsequent cardiovascular events, stroke, renal disease, heart failure, and mortality, particularly in the elderly. The authors review the mechanisms that contribute to pulse pressure and the association between pulse pressure, vascular risk factors, and outcomes.
Transradial Unprotected Left Main Coronary Artery Stenting in an Octogenarian With Severe Angina and Leriche Syndrome
Authors: Rigattieri Stefano , Ferraiuolo Giuseppe , Palamara Antonio , Loschiavo Paolo
Published: January 2007

Coronary artery disease in octogenarians is often diffuse and difficult to manage due to concomitant peripheral vascular disease. The authors describe a case in which an unprotected left main coronary artery was successfully treated by transradial stenting in a patient with severe angina and Leriche syndrome.
Minimally Invasive Mitral Valve Repair With and Without Robotic Technology in the Elderly
Authors: Tabata Minoru , Cohn Lawrence H.
Published: January 2007

An increasing number of elderly persons require mitral valve surgery, primarily for mitral regurgitation. Minimally invasive mitral valve repair, including robotic surgery, has been shown to be feasible and safe in the general population. Minimally invasive cardiac surgery is especially beneficial in the elderly because it decreases trauma and speeds recovery. The authors conducted a retrospective review of 123 cases of minimally invasive mitral valve repair in elderly patients aged 70 years and older and five robotic mitral valve repairs using the da Vinci surgical system (Intuitive Surgical, Inc., Sunnyvale, CA) in one octogenarian. The authors review their 9 years of experience with minimally invasive mitral valve repair in the elderly and compare and contrast other forms of surgery in the elderly, including robotic mitral valve repair.
Heart Failure at the End of Life: Symptoms, Function, and Medical Care in the Cardiovascular Health Study
Authors: Sullivan Mark D. , O'Meara Ellen S.
Published: January 2007

Among Cardiovascular Health Study participants who died from coronary heart disease, the authors compared those with incident and definite congestive heart failure (CHF) (n=60; 15%) and those with prevalent or probable CHF (n =70; 17.5%) to those with no history of CHF (n=198; 50%) concerning health status at the end of life. Both CHF groups had worse health status before death than the group without CHF. Patients in the CHF groups were more likely to use benzodiazepines (20% and 19% vs. 6%; p =0.001) and to rate their health as fair or poor (68% and 63% vs. 41%; p<0.001). They were more likely to be hospitalized (33% and 28% vs. 11%; p<0.001), to have activity restrictions (79% and 62% vs. 38%; p<0.001), and to report a wide array of physical symptoms. These data suggest that patients who die from coronary heart disease in the presence of CHF have greater need for hospice or palliative care than those with no history of CHF.
Telmisartan Plus HCTZ vs. Amlodipine Plus HCTZ in Older Patients With Systolic Hypertension: Results From a Large Ambulatory Blood Pressure Monitoring Study
Authors: Neldam Steen , Edwards Colin
Published: January 2007

Systolic hypertension often requires combination therapy. Few data exist comparing angiotensin receptor blocker plus diuretic therapy with other combinations in older patients. In a prospective, randomized, open‐label, blinded‐end point trial, patients (≥60 years of age) with predominantly systolic hypertension received telmisartan 40–80 mg or amlodipine 5–10 mg for 8 weeks, before the addition of hydrochlorothiazide (HCTZ) 12.5 mg for a further 6 weeks. Twenty‐four‐hour ambulatory blood pressure monitoring showed that telmisartan plus HCTZ (n =448) and amlodipine plus HCTZ (n =424) changed systolic blood pressure for the last 6 hours of the dosing interval by −18.3 and −17.4 mm Hg, respectively (p =0.2520). Over the 24‐hour period, telmisartan plus HCTZ was superior (−19.3 and −17.2 mm Hg, respectively; p =0.001) and provided higher systolic control rates (65.9% and 58.3%, respectively; p =0.0175). Adverse events (41.2% and 53.7%, respectively) and discontinuations (5.0% and 11.3%, respectively) were lower (p<0.0001) with telmisartan than with amlodipine, mainly due to peripheral edema (1.2% and 24.3%, respectively).
What Is the Optimal Reperfusion Strategy for Elderly Patients With Acute MI?
Authors: Orso Francesco , Pietro Maggioni Aldo
Published: January 2007

The overview of the Fibrinolytic Therapy Trialists' (FTT) Collaborative Group showed that, in more than 3000 elderly patients, thrombolytic treatment is effective in reducing mortality of patients with acute myocardial infarction with ST elevation within 12 hours from the onset of symptoms. Small‐scale clinical trials confirmed the superiority of primary percutaneous coronary intervention even in older patients. However, clinical practice largely differs from the setting of clinical trials and, specifically, with respect to primary percutaneous coronary intervention. As a consequence, the results observed with percutaneous coronary intervention in “real world” patients seem to be less favorable than those obtained in trials. For this reason, reperfusion therapy with fibrinolytic agents remains the first choice of therapy for ST elevation myocardial infarction in the majority of hospitals where direct percutaneous coronary intervention facilities are not available.
Lifestyle and Prevention of Cardiovascular Disease in the Elderly: An Italian Perspective
Authors: Abete Pasquale , Della Morte David , Mazzella Francesca , D'Ambrosio Daniele , Galizia Gianluigi , Testa Gianluca , Gargiulo Gaetano , Cacciatore Francesco , Rengo Franco
Published: January 2007

The life span of human beings is partially influenced by genetic factors, but outcomes of aging are profoundly influenced by lifestyle and other environmental factors. Age‐related modifications of the cardiovascular system are preserved by antiaging lifestyle interventions such as physical activity and caloric restriction. Accordingly, physical activity and low body mass index reduce mortality in older men with cardiovascular diseases. Several mechanisms have been proposed to explain the protective effect of lifestyle interventions against cardiovascular diseases in the elderly, including a reduction of vulnerability (i.e., the age‐related reduction of endogenous mechanisms protective against pathologic insults). The age‐related reduction of ischemic preconditioning, the most powerful endogenous protective mechanism against myocardial ischemia, is restored by both physical activity and caloric restriction. Thus, older persons can implement lifestyle practices that minimize their risk of death from cardiovascular diseases.
A Clinical Algorithm to Differentiate Heart Failure With a Normal Ejection Fraction by Pathophysiologic Mechanism
Authors: Kliger Chad , King Donald L. , Maurer Mathew S.
Published: January 2007

The incidence and prevalence of heart failure are increasing as the population ages. Epidemiologic studies demonstrate that more than half of heart failure patients have a normal ejection fraction. The pathophysiology of this disorder is not completely understood. It is primarily attributed to left ventricular diastolic dysfunction (a leftward‐ and upward‐shifted end‐diastolic pressure‐volume relation), where left ventricular diastolic chamber size is normal or reduced despite greater‐than‐normal filling pressures, resulting in reduced stroke volume and cardiac output. Using classic measures derived from pressure‐volume analysis, we delineate other possible combinations of the end‐systolic and end‐diastolic pressure‐volume relation, and hence possible pathophysiologic mechanisms that could underlie the syndrome of heart failure with normal ejection fraction. We propose an algorithm for identifying the primary pathophysiologic mechanism of heart failure in the setting of a normal ejection fraction using three simple factors: blood pressure, electrocardiographic/echocardiographic evidence of left ventricular hypertrophy, and left ventricular size. The application of this algorithm may aid in guiding management and targeting much‐needed therapies for this population.
Enrollment and Maintenance of Elderly Patients in Cardiovascular Clinical Trials
Authors: Wenger Nanette K.
Published: January 2007

This review addresses the paucity of data available to guide clinical cardiovascular management at advanced elderly age, a likely contributor to the lesser use of beneficial therapies in this population. Cardiovascular disease is the largest health burden of aged persons; this mandates inclusion of elderly persons in clinical research studies of preventive interventions, diagnostic procedures, pharmacotherapy, and high‐technology interventional procedures to ascertain their applicability to patients of advanced age. Relevant clinical outcomes include improvement in functional independence and quality of life, decrease in costly hospitalizations, and prolongation of meaningful life.
Why Cardioverter‐Defibrillator Implantation Might Not Be the Best Idea for Your Elderly Patient
Authors: Yarnoz Michael J. , Curtis Anne B.
Published: January 2007

Over the last decade, implantable cardioverter‐defibrillators (ICDs) have become a part of mainstream clinical practice, with improvements in survival in a broad range of patients. Given the overall limited life expectancy of elderly patients, their frequent comorbidities, and the complications associated with ICD implantation, it may not be reasonable to expect results with ICD implantation in the elderly to be comparable to that found in the clinical trials. In this paper, the authors review the available scientific literature and discuss why mainstream ICD use in the elderly may not be advisable.
Implantable Cardioverter‐Defibrillators Should Be Used Routinely in the Elderly
Authors: Boxton Alfred E.
Published: January 2007

Implantable cardioverter‐defibrillators (ICDs) reduce mortality in selected high‐risk populations by reducing the risk of sudden death. No clinical trial examining ICD efficacy has focused specifically on benefits and risks in the elderly, but all trials have included substantial numbers of older patients. The author addresses several issues: Is the risk of sudden death different for the elderly than in younger patients? Is ICD implantation feasible in the elderly? Is there evidence that ICD use in the elderly improves survival? The author's research indicates that while total mortality is higher for the elderly, there does not appear to be a specific predilection for arrhythmic death. Recent reports indicate that while ICDs can be implanted in a Medicare population, ICD implantation is associated with significant mortality (0.9%), as well as periprocedural complications (10.8%). In spite of the risks, both secondary and primary prevention trials demonstrate that the survival benefit associated with ICD use in the study populations was at least as great for elderly patients as for younger persons. Thus, published data support judicious ICD use in elderly patients at high risk for sudden death.
The tobacco Ntann12 gene, encoding an annexin, is induced upon Rhodoccocus fascians infection and during leafy gall development
Authors: VANDEPUTTE OLIVIER , LOWE YVES OUKOUOMI , BURSSENS SYLVIA , VAN RAEMDONCK DAMIEN , HUTIN DAVID , BONIVER DELPHINE , GEELEN DANNY , EL JAZIRI MONDHER , BAUCHER MARIE
Published: January 2007

Annexins are calcium‐binding proteins that have been associated in plants with different biological processes such as responses to abiotic stress and early nodulation stages. Until now, the implication of annexins during plant–pathogen interactions has not been reported. Here, a novel plant annexin gene induced in tobacco BY‐2 cell suspension cultures infected with the phytopathogenic bacterium Rhodococcus fascians (strain D188) has been identified. Expression of this gene, called Ntann12, is also induced, but to a lower extent, by a strain (D188‐5) that is unable to induce leafy gall formation. This gene was also induced in BY‐2 cells infected with Pseudomonas syringae but not in cells infected with Agrobacterium tumefaciens or Escherichia coli. Ntann12 expression was also found to be stimulated by abiotic stress, including NaCl and abscissic acid, confirming a putative role in stress signal transduction pathways. In addition, promoter‐GUS analyses using homozygous transgenic tobacco seedlings showed that the developmentally controlled expression of Ntann12 is altered upon R. fascians infection. Finally, up‐regulation of Ntann12 during leafy gall ontogenesis was confirmed by RT‐qPCR. Discussion is focused on the potential role of Ntann12 in biotic and abiotic stress responses and in plant development, both processes that may involve Ca2+‐dependent signalling.
The impetus for family‐centred early childhood intervention
Authors: Carpenter B.
Published: January 2007

In this article, the current climate of early intervention is considered, advocating the necessity for it to remain a cutting‐edge service that attends to the changing needs profiles of children and their families.

The article reviews the difficulties experienced by families in the UK, where, as the government acknowledges, life chances are still unequal. It emphasises that early interventions can increase the likelihood of the family being able to engage or re‐engage with mainstream societal services, thus reducing the long‐term costs to society.

It discusses the past and present UK policy context from 2004, when Sohns reported that the UK was the only country without a national policy of infrastructure in relation to early childhood intervention, until the present when, a raft of legislation is in place acknowledging its importance and the need for priority.

Central to many effective early intervention programmes is the goal of establishing shared communication in the infant–key carer dyad, using alternative communication and therapy‐based interventions. The article discusses parent‐inclusive programmes which meet the needs of both parents and children, and receive endorsement from parents.

Finally, the article considers evaluation of early childhood services, and the necessity of increasing the centrality of the family in service delivery in order to provide services which are integrated, relevant and efficacious.
Strong below‐ground competition shapes tree regeneration in invasive Cinnamomum verum forests
Authors: KUEFFER CHRISTOPH , SCHUMACHER EVA , FLEISCHMANN KARL , EDWARDS PETER J. , DIETZ HANSJÖRG
Published: January 2007

Plant species invading nutrient‐poor ecosystems are likely to have their greatest impact on the native plant community by competing for resources below‐ground. We investigated how root competition by an invasive tree, Cinnamomum verum, affects regeneration in nutrient‐poor tropical secondary forests, in the Seychelles.

We performed three trenching experiments to investigate the effects of severing the root systems of mature trees on the growth of juveniles. These experiments had the following objectives: (i) to compare the responses of native and invasive saplings to release from root competition; (ii) to compare how seedlings (< 50 cm tall) and saplings (> 50 cm tall) of C. verum respond to trenching; and (iii) to compare the response of C. verum seedlings to trenching in forest stands with and without C. verum as the dominant species.

The results indicate that the dense topsoil root mat produced by mature C. verum trees suppresses the growth of young trees, mainly by increasing competition for scarce nutrients. Growth responses to trenching were stronger for seedlings than saplings, and stronger for juveniles of invasive than of native species. We conclude that stands of C. verum exert a strong below‐ground filtering effect on seedling regeneration. This effect is likely to influence secondary forest succession by selectively reducing the establishment of invasive and small‐seeded species.

Because of the bias in invasion biology towards relatively nutrient‐rich, productive ecosystems, few studies have investigated the role of below‐ground resource competition in plant invasions. Our results for an infertile, phosphorus‐poor ecosystem show that root competition by an alien species can exert a strong influence on forest regeneration. We suggest that this mechanism may be of general importance in nutrient‐poor tropical forests invaded by alien tree species.
Dendrosomes: A New Preparation of Isolated Neurosecretory Dendrites
Authors: Row David V. , Morris John F. , Toescu Emil C.
Published: January 2007

To investigate secretion from dendrites of magnocellular neurosecretory neurons we have developed a preparation of isolated portions of the dendrites analogous to synaptosomes and neurosecretosomes. The dendrites of magnocellular neurons extend into the ventral glial lamina ventral and lateral to the nucleus. The ventral glial lamina is dissected out and gently homogenized to shear off portions of the dendrites. These re‐seal to form granule‐filled, membrane‐bound structures which we refer to as ‘dendrosomes’. Dendrosomes were recovered by differential centrifugation and identified by light and electron microscopy either in unlabelled preparations or by immunocytochemistry.

Stimulation of dendrosomes with 56 mM potassium in the presence of tannic acid, which preserves exocytosed granule cores so that they can be visualized electron microscopically, demonstrates that, in response to a depolarizing stimulus, dendrosomes are capable of secreting by exocytosis the neuropeptides oxytocin (OT) and vasopressin (VP) and their co‐packaged neurophysins.
A Comparison of the Effects of Medial Preoptic Electrical Versus Electrochemical Stimulation on Luteinizing Hormone‐Releasing Hormone Neuronal Responsiveness to Norepinephrine
Authors: Hartman Richard D. , Barraclough Charles A.
Published: January 2007

Recently, we reported that luteinizing hormone‐releasing hormone (LHRH) neurons of estrogen‐treated, ovariectomized rats have only limited responsiveness to norepinephrine (NE). These conclusions were based upon observations that NE, when infused intracerebroventricularly, produced only minor increases in plasma luteinizing hormone (LH), whereas, similar infusions following preliminary medial preoptic area (MPOA) electrochemical stimulation (ECS) markedly amplified LH secretion. One difficulty with this approach is that ECS produces an irritative lesion and deposits iron within the tissue, whereas, electrical stimulation (ES) does not have such effects. Accordingly, in the present study, we compared the effects of MPOA–ECS versus –ES on LHRH neuronal responsiveness to NE. While equivalent peak LH concentrations occurred within 15 min after MPOA–ECS or –ES, in the ECS group, LH release was sustained, whereas, it abruptly ceased upon termination of ES (at 15 min). The intracerebroventricular pulse infusion of NE at the time of peak LH secretion (30 min) in MPOA–ECS animals markedly amplified LH release. In these animals, plasma LH remained significantly elevated for 75 min before a decline was observed. In contrast, an infusion of NE at the time of maximal LH release in ES rats (16 min) did not augment LH secretion.

The second series of studies examined the effects of MPOA infusions of NE in animals receiving preoptic ES. A single infusion of NE 16 min after ES (i.e. one min after termination of ES) did not amplify LH release, but when two NE pulses were given at 5 and 16 min after beginning preoptic ES, peak plasma LH levels were maintained for an additional 30 min before a decline occurred. Pretreatment of rats with a yS‐adrenoreceptor antagonist (propranolol) or a monoamine oxidase inhibitor did not affect peak LH responses obtained after either MPOA–ES alone or combined with two pulses of NE infused into the MPOA at 5 and 16 min. We conclude that following cessation of MPOA–ES, LHRH neurons rapidly lose their responsiveness to NE, whereas, rats which received MPOA–ECS retain such responsiveness possibly due to the stimulative properties of the iron deposited by the ECS. Presumably, for NE to trigger an LH surge requires prior removal of some intrinsic inhibitory control which regulates LHRH neuronal responsiveness to NE.
Preoptic Unit Responses to Microelectrophoresis of Neurotensin and its Antiserum in Female Rats
Authors: Akema Tatsuo , Kimuraf Fukuko
Published: January 2007

We and other investigators have demonstrated the stimulation of luteinizing hormone secretion following the microinjection of neurotensin (NT) into the medial preoptic area in female rats. The present study electrophysiologically examined the action of the peptide in the same brain region. Microelectrophoresis of NT produced either excitation or inhibition in 24% of the medial preoptic neurons tested in oestrogen‐primed and unprimed ovariectomized animals. Effective blockade of NT‐induced excitatory and inhibitor unit responses by means of the simultaneous application of an antiserum to NT (anti‐NT) indicated that they were produced by specific actions of the peptide. In addition, anti‐NT by itself altered the spontaneous firing rate in some NT‐responsive cells. These findings are in accord with the hypothesis that the preoptic area is a site of the action of NT in the female rat.
Localization of the Endogenous Benzodiazepine Receptor Ligand Octadecaneuropeptide and Peripheral Type Benzodiazepine Receptors in the Rat Pituitary
Authors: Tong Yiai , Tonont Marie‐Christine , Désy Louise , Nicolast Pierre , Vaudryt Hubert , Pelletier Georges
Published: January 2007

An association of octadecaneuropeptide, an endogenous ligand at the benzodiazepine receptor, with the peripheral type benzodiazepine receptor has been reported in brain as well as a few peripheral tissues. In order to verify whether or not such an association occurs in the rat pituitary gland, we have proceeded to the immunocytochemical localization of octadecaneuropeptide as well as the autoradiographic localization of peripheral type benzodiazepine receptors in rat pituitary, octadecaneuropeptide immunoreactive material was found in high concentrations in the posterior lobe, whereas only a very few cells were labelled in the intermediate lobe. The anterior lobe did not show any specific staining. Immunoelectron microscopy revealed that in the posterior lobe labelling was restricted to pituicytes. Autoradiographic studies demonstrated a strong and uniform labelling in the posterior lobe after incubation with [3H] PK11195, a ligand selective for peripheral type benzodiazepine receptors. In the intermediate lobe, the autoradiographic reaction was restricted to a narrow band adjacent to the hypophysial cleft. No labelling was detected in the anterior lobe. These results demonstrate a close association between octadecaneuropeptide and peripheral type benzodiazepine receptors in the intermediate and posterior lobes of the rat pituitary gland.
The Effect of an Osmotic Stimulus on the Release of Neurohypophysial Hormones in the Cat: Preferential Release of Vasopressin with a Possible Involvement of the Area Postrema
Authors: Bissett G. W. , Chowdreyt H. S. , Feldberg W.
Published: January 2007

In cats anaesthetized with intravenous chloralose, the injection of 0.05 to 0.4 ml 1.54 M NaCl solution (hypertonic saline, HS) into a lateral cerebral ventricle caused a large release of vasopressin. The concentration of vasopressin greatly exceeded that of oxytocin in the same samples of plasma.

Vasopressin was also released when HS was injected into the fourth ventricle and into the cisterna magna from which there is no access in the cat to the ventricles, but it was less effective by these routes than when injected into a lateral ventricle in the same cat. This suggests a possible action of HS on circumventricular organs related to the third ventricle but also indicates an additional site of action reached from the subarachnoid space which would give access to the ventral and dorsal surfaces of the brainstem.

Vasopressin was not released on topical application of HS to the ‘nicotine sensitive area’ on the ventral surface of the brainstem where nicotine acts to release vasopressin without oxytocin.

Vasopressin, however, was released without detectable oxytocin on topical appliction of HS to the dorsal surface of the brainstem either outside the fourth ventricle or to the floor of the ventricle at its distal extremity, in the region of the obex.

A possible site where HS acts to cause a preferential release of vasopressin on injection into a lateral ventricle is the area postrema, a circumventricular organ which impinges on the walls of the fourth ventricle at the obex. Preferential release of vasopressin might then be mediated by a selective neural input, possibly through the nucleus of the tractus solitarius, from osmoreceptors in the area postrema to the vasopressin‐secreting cells in the supraoptic and paraventricular nuclei.
Galanin Interacts with Serotonin in Stimulating Prolactin Secretion in the Rat
Authors: Koshiyama Hiroyuki , Shimatsu Akira , Assadian Hossein , Hattori Naoki , Ishikawa Yasuhiro , Tanoh Tsutomu , Yanaihara Noboru , Kato Yuzuru , Imura Hiroo
Published: January 2007

The interaction of galanin (GAL) with serotonin (5‐HT) in the regulation of prolactin (PAL) secretion was investigated in urethaneanesthetized male rats. Intracerebroventricular administration of 5‐HT (1 and 10 μ g) and GAL (1 μ g) caused an increase in plasma PRL levels, but co‐administration of GAL did not show any additive effect on 5‐HT‐induced PRL secretion. Pretreatment with methysergide (0.25 mg/kg), a nonselective 5‐HT1 and 5‐HT2 receptor antagonist, partially inhibited the PRL increase induced by GAL. On the other hand, neither ketanserin (0.25 mg/kg), a selective 5‐HT2 receptor antagonist, nor ICS 205–930 (0.25 mg/kg), a selective 5‐HT3 receptor blocker, had any effect on GAL‐induced increase in PRL secretion. Parachlorophenylalanine (300 mg/kg), a 5‐HT synthesis inhibitor, however, caused a marked enhancement of PRL release induced by GAL, which was partially inhibited by a 5‐HT neurotoxin, 5, 6‐dihydroxytryptamine. Parachlorophenylalanine also caused a potentiation of 5‐HT‐induced PRL release, possibly by sensitizing 5‐HT receptors. These findings suggest that 5‐HT receptors are, at least partly, involved in GAL‐induced PRL release in the rat.
Gamma‐Aminobutyric Acid Modulation of Corticotrophin‐Releasing Factor‐41 Secretion from the Rat Hypothalamus in vitro
Authors: Tsagarakis S. , Rees L. H. , Besser G. M. , Grossman A.
Published: January 2007

There is increasing evidence for a centrally mediated inhibitory effect of the amino‐acid neurotransmitter y‐aminobutyric acid (GABA) on the hypothalamo‐pituitary‐adrenal axis. In the present study, the direct effect of GABA in modulating the release of the 41‐residue corticotrophin‐releasing factor (CRF‐41), the major CRF identified so far, was investigated in acute hypothalamic explants by utilizing previously validated incubation and assay techniques. While GABA (10‐7’to 10‐5 M) had no effect on basal CRF‐41 release (P > 0.05), it significantly suppressed K ‐ (28 mM)‐stimulated release in a dose‐dependent manner (P < 0.01). A similar inhibitory effect was observed with the GABA agonist muscimol (10‐7 to 10‐5 M). Noradrenaline (10‐6 M) ‐induced CRF‐41 release was also significantly inhibited by GABA 10‐6 M. The inhibitory effect of GABA on K+‐stimulated CRF‐41 secretion was completely. reversed by the GABA antagonists bicuculline and picrotoxin (10‐6 to 10‐5 M) in a dose‐dependent fashion. Both bicuculline and picrotoxin stimulated basal and K+ (28 mM)‐stimulated CRF‐41 release, indicating the presence of tonic inhibition by endogenous GABA in the basal state. Finally, GABA 10‐5 M was able to significantly inhibit the stimulated release of CRF‐41 from the isolated median eminence.

In summary, the present data provide strong evidence that GABA‐induced inhibition of the hypothalamo‐pituitary‐adrenal axis is mediated, at least in part, through an inhibitory action on CRF‐41 secretion. It is likely that these GABA receptors are located directly on CRF‐41 neurons, probably on nerve terminals in the median eminence.
Influence of Ovarian Steroids on the Ultrastructural Plasticity of the Adult Rat Supraoptic Nucleus Induced by Central Administration of Oxytocin
Authors: Montagnese Catherine , Poulain Dominique A. , Theodosis Dionysia T.
Published: January 2007

In earlier studies, we showed that continuous intracerebroventricular infusion of oxytocin, for several days, into the third ventricle of normally hydrated, non‐lactating adult female rats significantly reduced glial coverage of magnocellular oxytocinergic neurons in the hypothalamus. It also induced synaptic remodelling whereby many oxytocinergic neurons became synaptically contacted by the same presynaptic terminals (shared synapses). Such changes were closely similar to those observed in the oxytocinergic system when it is physiologically activated, as during parturition and lactation.

We now report that central oxytocin does not act alone to modify the ultrastructure of the magnocellular nuclei, but requires the concomitant action of sex steroids. Intracerebroventricular infusion of oxytocin was effective in inducing neuronal‐glial and synaptic changes only in supraoptic nuclei of female rats undergoing a prolonged diestrus, or in castrated female rats treated during the infusion period with daily intramuscular injections of progesterone for 4 days followed by 17β‐estradiol for 2 days. Infusion of oxytocin in rats with regular estrous cycles, or in castrated rats treated with progesterone or estrogen alone had no effect on the ultrastructure of the nucleus. Our observations also indicate that the action of oxytocin on the anatomy of its own neurons is very specific: only 4‐threonine‐oxytocin, a closely related oxytocin analogue, had an effect similar to that of oxytocin; vasopressin, 4‐threonine‐7‐glycine oxytocin and cholecystokinin left the magnocellular nuclei structurally unaltered.
Ontogeny of Diabetes Insipidus in the Brattleboro Rat: Morphological and Physiological Correlates
Authors: Pow D. V. , Morris J. F.
Published: January 2007

The homozygous Brattleboro rat is a mutant of the Long Evans rat which fails to produce assayable quantities of vasopressin. Somata of supraoptic magnocellular neurons from adult Brattleboro rats are hypertrophied relative to those from normally hydrated adult Long Evans rats. We have investigated, by light microscopic morphometric analysis of immunoperoxidase‐labelled vibratome sections, the postnatal growth of magnocellular neurons in normal Long Evans rats, and the relative hypertrophy of these cells in Brattleboro rats.

Morphometric analysis of the somata of immunoidentified oxytocinergic and vasopressinergic supraoptic magnocellular neurons from Long Evans rats aged between 1 and 140 days postnatum revealed that their somata increased rapidly in size only after 14 days; a time that coincides with the start of weaning, with a transient increase in serum osmolality, and with the onset of ability to produce hyperosmotic urine. Oxytocin‐ and vasopressin‐containing neurons in Long Evans rats achieved adult dimensions by 45 days postnatum. By contrast, somata of oxytocin neurons in the Brattleboro rat already showed significant hypertrophy relative to those in Long Evans rats at 7 days postnatum; hypertrophy continued until at least 140 days. The hypertrophy in the Brattleboro rat at 7 days was associated with markedly raised serum osmolality relative to that of age‐matched Long Evans rats between 1 and 14 days.
Diagnostic Markers for Neonatal Sepsis: Comparing C‐reactive Protein, Interleukin‐6 and Immunoglobulin M
Authors: Khassawneh M. , Hayajneh W. A. , Kofahi H. , Khader Y. , Amarin Z. , Daoud A.
Published: January 2007

This clinical study was conducted to evaluate the diagnostic value of C‐reactive protein (CRP), interlekin‐6 (IL‐6) and immunoglobulin M (IgM) in the early diagnosis of neonatal sepsis. The diagnostic values of each marker separately or in combinations were evaluated. The optimal cut‐off values of each marker in the diagnosis of neonatal sepsis were defined. Between December 2004 and March 2005, a total of 78 neonates at different ages with different diagnoses in a neonatal intensive care unit in North Jordan were enrolled. Patients were classified into ‘sepsis’ group, ‘probable sepsis’ group and ‘no sepsis’ group. Blood samples were collected for CRP, IL‐6 and IgM determination. A CRP value of 5 mg/l was the best among the three parameters with 95% sensitivity and 98% negative predictive value. Combination between parameters was helpful in enhancing the ability to diagnose sepsis. The best combination was CRP ≥ 5 mg/l and/or IgM of ≥20 mg/dl. We conclude that CRP, IL‐6 and IgM are helpful in the early diagnosis of Gram‐negative neonatal sepsis. However, CRP continues to be the best single test. The use of both CRP and IgM in combination was the most helpful in predicting Gram‐negative neonatal sepsis. We speculate a significant role of this combination in making decisions regarding antibiotics treatment and upgrading the level of medical care and observation in a setting where Gram‐negative micro‐organisms are causing the majority of neonatal infections.
Induction of CD16+ CD56bright NK Cells with Antitumour Cytotoxicity not only from CD16− CD56bright NK Cells but also from CD16− CD56dim NK Cells
Authors: Takahashi E. , Kuranaga N. , Satoh K. , Habu Y. , Shinomiya N. , Asano T. , Seki S. , Hayakawa M.
Published: January 2007

The aim of this study was to examine the effect of cytokines on different subsets of NK cells, while especially focusing on CD16− CD56dim cells and CD16− CD56bright cells. When human peripheral blood mononuclear cells (PBMC) were cultured with a combination of IL‐2, IL‐12 and IL‐15 for several days, a minor population of CD56bright NK cells expanded up to 15%, and also showed potent cytotoxicities against various cancer cells. Sorting experiments revealed that unconventional CD16− CD56+ NK cells (CD16− CD56dim NK cells and CD16− CD56bright NK cells, both of which are less than 1% in PBMC) much more vigorously proliferated after cytokine stimulation, whereas predominant CD16+ CD56dim NK cells proliferated poorly. In addition, many of the resting CD16− CD56bright NK cells developed into CD16+ CD56bright NK cells, and CD16− CD56dim NK cells developed into CD16− CD56bright NK cells and also further into CD16+ CD56bright NK cells by the cytokines. CSFE label experiments further substantiated the proliferation capacity of each subset and the developmental process of CD16+ CD56bright NK cells. Both CD16− CD56dim NK cells and CD16− CD56bright NK cells produced large amounts of IFN‐γ and Fas‐ligands. The CD16+ CD56bright NK cells showed strong cytotoxicities against not only MHC class I (−) but also MHC class I (+) tumours regardless of their expression of CD94/NKG2A presumably because they expressed NKG2D as well as natural cytotoxicity receptors. The proliferation of CD16+ CD56bright NK cells was also induced when PBMC were stimulated with penicillin‐treated Streptococcus pyogenes, thus suggesting their role in tumour immunity and bacterial infections.
Digestion, Absorption and Tissue Distribution of Ovalbumin and Palmitoyl‐ovalbumin: Impact on Immune Responses Triggered by Orally Administered Antigens
Authors: Oliveira F. M. , Dos Santos E. M. , Alves A. C. , Campana‐Pereira M. A. , Ramaldes G. A. , Cardoso V. N. , Ruiz‐de‐Souza V. , Gontijo C. M.
Published: January 2007

Previous work in this laboratory has demonstrated that ovalbumin coupled to palmitoyl residues (palmitoyl‐Ova) does not induce oral tolerance. The present study sought to determine whether this coupling affects digestion, absorption and transfer of antigen. Ova and palmitoyl‐Ova were shown to be digested differently in vitro by proteolytic enzymes and presented different tissue distribution kinetics after being labelled with 99mtechnetium and orally administered to animals. Palmitoyl‐Ova remained longer in the stomach, while native Ova was quickly transferred to the gut and other organs. After 3 h, higher levels of palmitoyl‐Ova were found in the blood, Peyer's patches, mesenteric lymph nodes, liver and, especially, the spleen, which appears to be essential for immunization with palmitoyl‐Ova. In fact, splenectomized mice treated orally with palmitoyl‐Ova became tolerant, while tolerance to Ova was not affected. Thus, palmitoyl coupling was demonstrated to affect antigen digestion, absorption and transport. This is the first time that the spleen has been shown to be required for oral immunization with palmitoyl‐Ova.
TLR2 but not TLR4 Signalling is Critically Involved in the Inhibition of IFN‐γ‐induced Killing of Mycobacteria by Murine Macrophages
Authors: Arko‐Mensah J. , Julián E. , Singh M. , Fernández C.
Published: January 2007

Gamma‐interferon (IFN‐γ) plays a determinant role in activating macrophages that are critical to control Mycobacterium tuberculosis infection. However, M. tuberculosis can escape killing by attenuating the response of macrophages to IFN‐γ by blocking the transcription of a subset of IFN‐γ inducible genes. This inhibition occurs after signalling through Toll‐like receptor 2 (TLR2). While most studies have investigated the inhibition of IFN‐γ responsive genes after TLR2 signalling, the present study focuses on the functional implications of inhibition of IFN‐γ signalling in macrophages with regard to mycobacteria killing. Here, we provide evidence that exposure of the murine macrophage cell line J774 to the TLR2 ligands; 19‐kDa or zymosan, but not the TLR4 ligand LPS, inhibits IFN‐γ‐induced killing of Mycobacterium bovis Bacillus Calmette–Guérin (BCG). Moreover, exposure of bone marrow‐derived macrophages (BMM) from TLR4‐deficient and wild‐type (WT), but not from TLR2‐deficient mice to 19‐kDa lipoprotein (19‐kDa) or zymosan, results in an impairment of IFN‐γ‐mediated killing. We demonstrate that 19‐kDa and zymosan inhibit the ability of IFN‐γ to activate murine macrophages to kill BCG without inhibiting nitric oxide (NO) or tumour necrosis factor (TNF) production. Finally, we demonstrate that the inhibitory effect of 19‐kDa on IFN‐γ signalling is overcome with increasing amounts of IFN‐γ indicating that the refractoriness could be reversed at optimal IFN‐γ concentrations. The critical role of TLR2 but not TLR4 signalling in the inhibition of IFN‐γ promoted killing of mycobacteria is discussed.
Myzus persicae (green peach aphid) feeding on Arabidopsis induces the formation of a deterrent indole glucosinolate
Authors: Kim Jae Hak , Jander Georg
Published: January 2007

Cruciferous plants produce a wide variety of glucosinolates as a protection against herbivores and pathogens. However, very little is known about the importance of individual glucosinolates in plant defense and the regulation of their production in response to herbivory. When Myzus persicae (green peach aphid) feeds on Arabidopsis aliphatic glucosinolates pass through the aphid gut intact, but indole glucosinolates are mostly degraded. Although aphid feeding causes an overall decrease in Arabidopsis glucosinolate content, the production of 4‐methoxyindol‐3‐ylmethylglucosinolate is induced. This altered glucosinolate profile is not a systemic plant response, but is limited to the area in which aphids are feeding. Aphid feeding on detached leaves causes a similar change in the glucosinolate profile, demonstrating that glucosinolate transport is not required for the observed changes. Salicylate‐mediated signaling has been implicated in other plant responses to aphid feeding. However, analysis of eds5, pad4, npr1 and NahG transgenic Arabidopsis, which are compromised in this pathway, demonstrated that aphid‐induced changes in the indole glucosinolate profile were unaffected. The addition of purified indol‐3‐ylmethylglucosinolate to the petioles of cyp79B2 cyp79B3 mutant leaves, which do not produce indole glucosinolates, showed that this glucosinolate serves as a precursor for the aphid‐induced synthesis of 4‐methoxyindol‐3‐ylmethylglucosinolate. In artificial diets, 4‐methoxyindol‐3‐ylmethylglucosinolate is a significantly greater aphid deterrent in the absence of myrosinase than its metabolic precursor indol‐3‐ylmethylglucosinolate. Together, these results demonstrate that, in response to aphid feeding, Arabidopsis plants convert one indole glucosinolate to another that provides a greater defensive benefit.
The effects of various irradiation doses on the growth and differentiation of marrow‐derived human mesenchymal stromal cells
Authors: Li Jing , Kwong Dora L. W. , Chan Godfrey C‐F.
Published: January 2007

Abstract:  Mesenchymal stromal cells (MSC) are progenitors of mesenchymal tissues including bones. Irradiation can damage the osteogenic activity of human marrow by suppressing osteoblasts leading to post‐irradiation osteoporosis. However, the effect of therapeutic irradiation on MSC remains unexplored. We investigated the effects of various doses of X‐ray irradiation on human MSC (hMSC) by measuring its post‐irradiation proliferation and differentiation activities. Standard immunophenotypes and differentiating functions of the MSC were determined. Irradiation inhibited proliferation of hMSC up to two wk post‐irradiation but thereafter, those residual surviving cells regained their normal proliferation rate. Bone forming activity as reflected by alkaline phosphatase (ALP) and calcium deposition were both reduced in a dose‐dependent fashion. Maximum suppressive effect on osteogenic activity was noted in MSC treated with high‐dose irradiation (12 Gy). Adipocyte percentage was also reduced by 50% in cultures that received >4 Gy. Attempts to protect the irradiated cells with 1 μm all‐trans retinoic acid did not show any beneficial effect on MSC proliferation and differentiation. The direct impairment of proliferation and osteogenic differentiation potential of MSC by irradiation may contribute partly to the post‐transplant osteoporosis.