bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucocorticoid manipulations in free‐living animals: considerations of dose delivery, life‐history context and reproductive state
Authors: Crossin Glenn T. , Love Oliver P. , Cooke Steven J. , Williams Tony D.
Published: May 2015

Experimental glucocorticoid (GC) manipulations can be useful for identifying the mechanisms that drive life‐history and fitness variation in free‐living animals, but predicting the effects of GC treatment can be complicated. Much of the uncertainty stems from the multi‐faceted role of GCs in organismal metabolism, and their variable influence with respect to life‐history stage, ecological context, age, sex and individual variation.

Glucocorticoid hormones have been implicated in the regulation of parental care in many vertebrate taxa but in two seemingly contradictory ways, which sets up a potential GC‐induced ‘reproductive conflict’. Circulating GCs mediate adaptive physiological and behavioural responses to stressful events, and elevated levels can lead to trade offs between reproductive effort and survival (e.g. the current reproduction vs. survival hypothesis). The majority of studies examining the fitness effects of GC manipulations extend from this hypothesis. However, when animals are not stressed (likely most of the time) baseline GCs act as key metabolic regulators of daily energy balance, homoeostasis, osmoregulation and food acquisition, with pleiotropic effects on locomotor activity or foraging behaviour. Slight increases in circulating baseline levels can then have positive effects on reproductive effort (e.g. the ‘cort’ fitness/adaptation hypotheses), but comparatively few GC manipulation studies have targeted these small, non‐stress induced increases.

We review studies of GC manipulations and examine the specific hypotheses used to predict the effects of manipulations in wild, breeding vertebrates. We argue that given the dichotomous function of GCs the current ‘reproduction vs. survival’ paradigm is unnecessarily restrictive and predicts only deleterious GC effects on fitness. Therefore, a broader set of hypotheses should be considered when testing the fitness effects of GC manipulations.

When framing experimental manipulation studies, we urge researchers to consider three key points: life‐history context (e.g. long vs. short lived, semelparous vs. iteroparous, etc.), ecological context and dose delivery.
Introduction: the power of example
Authors: Højer Lars , Bandak Andreas
Published: May 2015

It is the contention of this introduction that examples are important prisms through which both reality and anthropological analysis are thought and, equally importantly, reconfigured. The aim of the introduction is to redress the theoretical disregard for exemplification by exploring the persuasive and evocative power – positive and negative – of ‘examples’ in social and academic life while also proposing exemplification as a distinct anthropological way of theorizing. Such theorizing points to a ‘lateral’ rethinking of the relation between the particular and the general. Our central argument is that examples highlight the precarious tension between the example as ‘example’ and the example as ‘exemplar’. All contributions to this special issue, in one way or another, explore this tension between the unruliness of examples and the stability‐enhancing power of exemplarity. The introduction further proposes that the example serves to confuse ontological divides, such as the one between theory and ethnography, and also draws attention to the fact that theory is as much suggestive as descriptive.
An Integrative Literature Review of the Factors That Contribute to Professional Nurses and Midwives Making Sound Clinical Decisions
Authors: ten Ham Wilma , Ricks Esmeralda J. , van Rooyen Dalena , Jordan Portia J.
Published: May 2015

Purpose

To identify available literature concerning the factors that contribute to nurses and midwives making sound clinical decisions.

Method

This is an integrative literature review.

Findings

Thirty‐eight articles revealed four main domains that influence nurses’ and midwives’ clinical decision making—nurses and midwives’ personal characteristics (n = 30), e.g., clinical experience; organizational factors (n = 26), e.g., colleagues; patient characteristics (n = 26), e.g., physical and clinical status; and environmental factors (n = 9), e.g., time. These four domains of factors combined influence sound clinical decision making in the context of nursing and midwifery.

Conclusions

Understanding the role of the factors influencing clinical decision making will help to improve patient and health outcomes.

Practice Implications

Further understanding about the extent of the impact some factors have on clinical decision making is needed.
Malignant hyperthermia, a Scandinavian update
Authors: Broman M. , Islander G. , Müller C. R.
Published: May 2015

Background

Malignant Hyperthermia (MH) is a rare pharmacogenetic disorder, triggered by halogenated anesthetics and/or succinylcholine. In susceptible individuals, these drugs can activate an explosive life threatening clinical reaction. Leading symptoms are hypercarbia, muscle rigidity, and metabolic acidosis. MH is inherited in an autosomal‐dominant manner and linked to mutations in the large ryanodine 1 gene (RYR1) gene in the majority of cases. Very few MH patients have been found to carry mutations in the CACNA1S gene.

Methods

For this review a large litterature search was carried out and the Swedish MH database consisting of 436 probands who have undergone in vitro muscle contraction test (IVCT) during 1984–2014 was analyzed.

Results

Twelve different MH causative mutations have been found in Swedish patients so far. These mutations lead to a disturbed calcium balance in striated muscle tissue. A muscle biopsy for the IVCT or finding of an approved causative mutation are required for the diagnosis.

Conclusion

A Malignant Hyperthermia susceptible (MHS) patient should be anesthetized with trigger‐free anesthesia. There are a few reports of MH‐like reactions in patients unrelated to anesthesia. The outcome is dependent on early recognizing of the reaction and fast disconnection of the trigger agents and administration of dantrolene.
Using Transdermal Alcohol Monitoring to Detect Low‐Level Drinking
Authors: Roache John D. , Karns Tara E. , Hill‐Kapturczak Nathalie , Mullen Jillian , Liang Yuanyuan , Lamb Richard J. , Dougherty Donald M.
Published: May 2015

Background

Several studies demonstrate the utility of Alcohol Monitoring Systems’ (AMS) transdermal alcohol concentration (TAC) monitor to objectively quantify drinking. AMS standard criteria (i.e., TAC >0.02 g/dl) used for drinking detection are deliberately conservative, but consequently only detect drinking equivalent to 5 or more standard drinks. Our study sought to characterize the sensitivity of TAC measurement to detect low‐level drinking defined as the consumption of 1 to 3 beers.

Methods

Data were pooled from 3 studies giving controlled doses of 1, 2, 3, 4, and 5 Corona© beers (12 oz = 0.92 standard units) to 32 male and 29 female research volunteers wearing TAC monitors under controlled conditions. Analyses describe the sensitivity to detect drinking at various peak TAC thresholds beginning with any positive reading >0 g/dl, and then using TAC thresholds of 0.02 and 0.03 g/dl.

Results

Nearly 40% of participants drinking 1 beer did not have a positive TAC reading. However, positive TAC readings were observed in more than 95 and in 100% of participants drinking 2 and 3 or more beers, respectively. The probability of peak TAC detection was a positive function of the number of beers consumed and a negative function of the minimum TAC threshold for detection. Drinking was somewhat more likely to be detected in females than males drinking 2 to 5 beers, but not after 1 beer. Use of AMS standard criteria only reliably detected the consumption of 5 beers, and 45.9% of all occasions of drinking 1 to 3 beers were undetected using 0.02 g/dl as a threshold.

Conclusions

Peak TAC levels between 0 and 0.02 g/dl must be considered to detect the low‐level drinking of 1 to 3 standard drinks, and such thresholds are necessary when researchers and clinicians want to detect low‐level drinking.
Mycosis fungoides and Sézary syndrome: Current challenges in assessment, management and prognostic markers
Authors: Hughes Charlotte FM , Newland Kate , McCormack Christopher , Lade Stephen , Prince H Miles
Published: May 2015

Mycosis fungoides and Sézary syndrome are the most common variants of the cutaneous T‐cell lymphomas. Assessment of a patient with a suspected diagnosis requires thorough history taking and physical examination, in combination with skin biopsy. In some cases flow cytometry, molecular studies and imaging are also required in order to diagnose and stage the disease. Staging is derived from the tumour‐node‐metastasis‐blood classification and is currently our best attempt to stratify prognosis and hence guide management in this complex disease. Many other clinical, biological and pathological factors may help to distinguish groups at risk and predict prognosis more accurately. Management remains heavily guided by staging, such that patients with early‐stage disease generally begin treatment with skin‐directed or local therapies and those with advanced‐stage disease have many treatment options, including chemotherapy, the use of biological agents, local and total body radiotherapy, as well as haematopoietic stem cell transplantation. Besides staging, many other patient‐related factors influence the treatment strategy, particularly where symptom relief is paramount. There are many challenges remaining in the study of Mycosis fungoides and Sézary syndrome and, given the rarity of the disease, concerted worldwide efforts are required to conduct efficient and effective research.
The role of cyclooxygenase-2 and prostaglandin E2 in the pathogenesis of cutaneous lichen planus
Authors: El-Rifaie A. A. , Rashed L. A. , Doss R. W.
Published: May 2015

Background

Lichen planus (LP) is an inflammatory disease of the skin and mucous membranes. Autoimmunity has been suggested as a possible cause of this disease. The cyclooxygenase enzymes (COX-1, COX-2) are the key enzymes in the conversion of arachidonic acid into prostaglandins. Prostaglandin E2 (PGE2), a key product of COX-2, has an immunomodulatory role.

Aim

To map levels of COX-2 and PGE2 in cutaneous LP lesions and evaluate their role in the pathogenesis of the disease.

Methods

In total, 31 patients with classic cutaneous LP and 30 age- and sex-matched healthy controls were enrolled. Skin biopsies were taken from the lesional and nonlesional skin of patients, and from the normal skin of controls. COX-2 mRNA expression was detected by real-time reverse transcription quantitative PCR, and PGE2 was detected by ELISA in skin biopsies from patients and controls.

Results

Our analysis revealed a significantly higher expression of COX-2 mRNA and PGE2 in the LP skin biopsies compared with the control biopsies (P < 0.001 and P < 0.001, respectively). Lesional biopsies showed significantly higher expression of COX-2 mRNA and PGE2 compared with nonlesional biopsies. The levels of COX-2 and PGE2 were not found to be correlated with age, sex or disease duration.

Conclusions

COX-2 and its product PGE2 are strongly expressed in LP skin lesions, indicating that they have a role in the pathogenesis of LP through their immunomodulatory effects.
Land Ownership as an Urban Employment Disincentive for Rural Migrants in China
Authors: Rao Can , Yu Jingwen , Zhu Hongfei
Published: May 2015

When landowning rural migrants in urban areas in China become unemployed, they retain the option to return home to agricultural work. As a result, the opportunity cost of the loss of employment for these migrants declines. In addition, the potential wealth arising from compensation for expropriated rural land increases significantly with ongoing urbanization in China. This weakens the incentive for landowning rural migrants to work as hard in urban employment as they might otherwise. In this paper, we employ the Floating Population Dynamic Monitoring Survey for Beijing, Shanghai, and Guangzhou in 2012, as surveyed by the Municipal Population and Family Planning Commission to assess the employment disincentives induced by rural land ownership. We find that compared with landless rural migrants, landowning rural migrants generally have less job stability and lower salaries.
Entrepreneurship and Job‐relatedness of Human Capital
Authors: Ohyama Atsushi
Published: May 2015

This paper proposes a theory according to which entrepreneurial ability to deal with the adoption of new technology is a key determinant of value creation in entrepreneurship. In a single conceptual framework, we demonstrate that a bimodal pattern of entrepreneurial entry emerges: both individuals possessing high job‐related human capital and individuals with low job‐related human capital enter entrepreneurship. Our empirical analysis, using information from the Scientists and Engineers Statistical Data System, shows that entrepreneurial earnings crucially depend on the level of job‐related human capital.
Feeding wild birds in gardens: A test of water versus food
Authors: Miller Kelly K. , Blaszczynski Veronika N. , Weston Michael A.
Published: May 2015

Bird feeding in residential gardens is an increasingly popular human–wildlife interaction. In Australia, the practice is discouraged by most government and nongovernment wildlife conservation agencies, although advice varies and the most common recommendation is to provide water and habitat for birds rather than supplementary food. This study compares bird abundance and diversity when residents in a Melbourne municipality provide water for birds versus food. Bird abundance was greater when food was provided compared with water, but avian assemblages did not differ.
Progress with restoration and management of Eastern Suburbs Banksia Scrub on North Head, Sydney
Authors: Lambert Geoff , Lambert Judy
Published: May 2015

How has management of Eastern Suburbs Banksia Scrub vegetation on North Head progressed over the last 6 years and what insights can be gained from recent treatments?
The resilience of migrant money: how gender, generation and class shape family remittances in Peruvian migration
Authors: PAERREGAARD KARSTEN
Published: May 2015

Scholars and policy makers have argued that because altruism drives remittance sending, migrant money is more resilient to uncertainty than other capital flows. In this article, I question this assumption through ethnographic examination of remittance sending by Peruvian migrant families. When in their lives do Peruvian migrants start to remit? Who are the recipients? What is the purpose of their remittances? How long do they last and why do they stop? I argue that, to answer these questions, we need to investigate how migrants make remittance commitments to different household members, how these attribute value to the remittances and how this value becomes the object of negotiation and contestation. The findings indicate that remittances reinforce existing relations of gender, generation and class in Peruvian society and suggest that while short‐lived remittances are based on contractual commitments and driven by altruism, long‐term remittances are based on emotional commitments and driven by both non‐utilitarian and utilitarian motives.
Heme‐mediated inhibition of Bach1 regulates the liver specificity and transience of the Nrf2‐dependent induction of zebrafish heme oxygenase 1
Authors: Fuse Yuji , Nakajima Hitomi , Nakajima‐Takagi Yaeko , Nakajima Osamu , Kobayashi Makoto
Published: May 2015

The induction of the gene encoding heme oxygenase 1 (Hmox1, HO‐1) by Nrf2 is unique compared with other Nrf2 targets. We previously showed that the Nrf2a‐mediated induction of zebrafish hmox1a was liver specific and transient. We screened transcription factors that could repress the induction of hmox1a but not other Nrf2a targets and concluded that Bach1b was a prime candidate. In bach1b‐knocked‐down larvae, the induction of hmox1a was observed ectopically in nonliver tissues and persisted longer than normal fish, suggesting that Bach1 is the only regulator for both the liver‐specific and transient induction of hmox1a. Co‐knockdown of bach1b with its co‐ortholog bach1a enhanced these effects. To determine why Bach1 could not repress the hmox1a induction in the liver, we analyzed the effects of a heme biosynthesis inhibitor, succinylacetone, and a heme precursor, hemin. Succinylacetone decreased the Nrf2a‐mediated hmox1a induction, whereas pre‐treatment with hemin caused ectopic induction of hmox1a in nonliver tissues, implying that the high heme levels in the liver may release the repressive activity of Bach1. Our results suggested that Bach1 regulates the liver specificity and transience of the Nrf2a‐dependent induction of hmox1a and that heme mediates this regulation through Bach1 inhibition based on its level in each tissue.
Monitoring and evaluation of patient involvement in clinical practice guideline development: lessons from the Multidisciplinary Guideline for Employment and Severe Mental Illness, the Netherlands
Authors: van der Ham Alida J. , van Erp Nicole , Broerse Jacqueline E.W.
Published: May 2015

Objective

The aim of this study was to gain better insight into the quality of patient participation in the development of clinical practice guidelines and to contribute to approaches for the monitoring and evaluation of such initiatives. In addition, we explore the potential of a dialogue‐based approach for reconciliation of preferences of patients and professionals in the guideline development processes.

Methods

The development of the Multidisciplinary Guideline for Employment and Severe Mental Illness in the Netherlands served as a case study. Methods for patient involvement in guideline development included the following: four patient representatives in the development group and advisory committee, two focus group discussions with patients, a dialogue session and eight case studies. To evaluate the quality of patient involvement, we developed a monitoring and evaluation framework including both process and outcome criteria. Data collection included observations, document analysis and semi‐structured interviews (n = 26).

Results

The quality of patient involvement was enhanced using different methods, reflection of patient input in the guideline text, a supportive attitude among professionals and attention to patient involvement throughout the process. The quality was lower with respect to representing the diversity of the target group, articulation of the patient perspective in the GDG, and clarity and transparency concerning methods of involvement.

Conclusions

The monitoring and evaluation framework was useful in providing detailed insights into patient involvement in guideline development. Patient involvement was evaluated as being of good quality. The dialogue‐based approach appears to be a promising method for obtaining integrated stakeholder input in a multidisciplinary setting.
Studies on renal vasomotion
Authors: CONCHA J. , NORRIS BERYL
Published: May 2015

The present investigation was made on the left kidney of the dog. The animals were anaesthetized intravenously with pentobarbitone (30 mg/kg) and the kidneys were perfused with saline at room temperature (20°–22° C). The renal innervation was untouched.

Stimulation of the left splanchnic major nerve at T10‐T12, and of the renal nerves, consistently caused renal vasoconstriction.

Repeated stimulation of both supradiaphragmatic vagi failed to induce any vasomotion in the kidney.

The vasoconstrictor effect was not blocked by either nicotine or hexamethonium even in enormous doses (30,000 μg). This may indicate that renal ganglia do not exist, for these ganglion blockers would prevent transmission across the ganglia.

Kidney perfusate, re‐injected into the kidney after vasoconstriction induced by stimulation of the renal nerves, brought about a notable reduction in outflow. This effect was not observed when perfusate from a non‐stimulated kidney was used. This points to the release of a vasoconstrictor substance after nervous stimulation.

Acetylcholine (ACh) in concentrations ranging from 0.001 μg/ml. caused a reduction in renal outflow. Thresholds were extremely variable. Higher concentrations of ACh (100–1,000 μg/ml.) often induced vasodilatation. The vasoconstrictor effect of ACh was not blocked by atropine.

Nicotine and hexamethonium (10,000–30,000 μg) induced blockade which elevated the threshold for ACh to values of 1,000 μg/ml.

Noradrenaline (0.0001 μg/ml.) induced a strong renal vasoconstriction.

Hydergine (5–10 ml. solutions in concentrations ranging from 15 to 30 μg/ml.) blocked the renal response to nerve stimulation. This suggests that the nature of the renal innervation is adrenergic.

In diseased kidneys which show reduction of the lumen of the arterioles, the thresholds for ACh, nicotine and noradrenaline are greatly increased, which might explain why we failed to show any effect of these drugs on renal vasomotion in several kidneys, many of which were not examined histologically.

The collision technique was applied in an attempt to discover the nature of the fibres activated by ACh. It was found that ACh greatly reduced the size of the action potentials generated by splanchnic stimulation. This would seem to indicate that these impulses are conducted antidromically by sympathetic postganglionic fibres.

These findings are discussed in relation to the hypothesis that the renal innervation is chiefly adrenergic and that ACh acts as a sympathetic transmitter, liberating noradrenaline, and that this effect is blocked at postganglionic endings, or at some structure intervening between adrenergic nerve endings and the effector cells, or at sensory nerve endings.
The actions of caerulein on gastric secretion of the dog and the rat
Authors: BERTACCINI G. , ENDEAN R. , ERSPAMER V. , IMPICCIATORE M.
Published: May 2015

Caerulein, as expected from its amino‐acid composition and sequence, has a potent stimulant action on gastric secretion in the dog, the rat and the frog.

In the denervated fundic pouch of the dog, caerulein increases the rate of flow of gastric juice and the outputs of acid and pepsin. Acid concentration and pepsin concentration in caerulein‐produced juice are generally greater than in control juice. The threshold subcutaneous dose of caerulein is 0.15–0.5 μg/kg and the threshold rate of intravenous infusion 0.25–0.5 μg/kg per hr. Rapid intravenous injection is ineffective. On a molar basis, caerulein is approximately twice as active as human gastrin I on volume and acid output of the gastric pouch and 4 times as active on pepsin output.

Sustained acid secretion of the fundic pouch produced by histamine infusion is inhibited by caerulein, administered either intravenously or subcutaneously. In turn, acid secretion elicited by caerulein is inhibited by atropine.

In the rat, the activity ratio of caerulein to human gastrin I is 7–30, calculated on a molar basis, and is thus considerably greater than in the dog. Further, caerulein is 3 times more active than cholecystokinin‐pancreozymin. Tested on the perfused stomach preparation of the rat, the threshold dose of caerulein by rapid intravenous injection is 25 ng/kg, by intravenous infusion 0.25 μg/kg per hr, and by subcutaneous injection 0.25 to 0.5 μg/kg.

The activity of caerulein is sharply reduced by pretreatment of the rats with the histamine liberator 48/80 and potentiated by pretreatment with the diamine oxidase inhibitor aminoguanidine. When caerulein is given by rapid intravenous injection during a priming infusion of histamine its effect is enhanced and considerably prolonged.

The isolated mucosa of the frog stomach is extremely sensitive to caerulein which, in a concentration of a few pg/ml., stimulates active transport of chloride.

Qualitative and quantitative differences in the action of gastrin and caerulein are pointed out, and particular emphasis is laid on the importance of esterification of the tyrosyl residue for the biological activity of caerulein.
The cholinergic properties of some amino‐acid esters and amides
Authors: BARRASS B. C. , BRIMBLECOMBE R. W. , PARKES D. C. , RICH P.
Published: May 2015

Several amino‐acid esters and amides have been prepared and their toxicological and pharmacological properties have been investigated. Some of the quaternary esters and amides were lethal to mice at doses below 1 mg/kg; this lethality was usually associated with high nicotinic activity. None of the compounds showed high muscarinic activity.

The cause of death was asphyxia due to paralysis of the respiratory muscles, but at higher doses there was also failure of the medullary respiratory centre.

Administration of sub‐lethal doses of nicotine to mice was shown to protect the animals from subsequent lethal doses of nicotine. The amino‐acid esters did not share this property, nor was there any cross‐protection between nicotine and these esters.

The possible nature of the nicotinic receptor is discussed with reference to these compounds and other known nicotinic agents. A tentative suggestion is made that nicotinic activity can result from a two‐point interaction between the drug and the receptor.
A comparison of the haemodynamic effects of propranolol, 4‐hydroxypropranolol and practolol in anaesthetized dogs
Authors: FITZGERALD J. D. , O'DONNELL STELLA R. ,   WITH THE TECHNICAL ASSISTANCE OF MARILYN AUSTIN
Published: May 2015

The haemodynamic effects of propranolol, practolol and 4‐hydroxypropranolol have been compared in anaesthetized dogs both at free heart rates and at heart rates fixed by electrical pacing. All three drugs produced a fall in heart rate at the lowest dose of 009 mg/kg.

Practolol caused less change in dP/dt, cardiac output and blood pressure than did propranolol. 4‐Hydroxypropranolol had intermediate effects. Since the changes in dP/dt caused by these three drugs were still present when the heart rate was fixed by pacing, it is concluded that these were independent of changes in heart rate.

The fact that practolol and 4‐hydroxypropranolol cause less change in haemodynamic function than propranolol may be associated with the intrinsic sympathomimetic activity possessed by the first two of these drugs.
THE INTERACTION OF NEUROLEPTIC AND MUSCARINIC AGENTS WITH CENTRAL DOPAMINERGIC SYSTEMS
Authors: KELLY P.H. , MILLER R.J.
Published: May 2015

The effect of muscarinic and neuroleptic agents on the turning behaviour induced by methamphetamine and apomorphine in rats with unilateral lesions of the substantia nigra induced by 6‐hydroxydopamine has been examined.

Turning towards the side of the lesion induced by (+)‐methamphetamine (5 mg/kg) was inhibited by α‐flupenthixol (1 mg/kg) and α‐clopenthixol (8 mg/kg) but not by high doses of their β‐isomers.

Turning was inhibited by chlorpromazine (4 mg/kg) and pimozide (0.2 mg/kg). Thioridazine and clozapine (16 mg/kg) were ineffective. Turning in the same direction produced by scopolamine (10 mg/kg) was also inhibited by α‐flupenthixol (1 mg/kg) and pimozide (0.25 mg/kg).

Turning produced by methamphetamine (5 mg/kg) was inhibited by oxotremorine (0.75 mg/kg) even in the presence of methylatropine (5 mg/kg).

Turning away from the side of the lesion induced by apomorphine (0.1 mg/kg) was inhibited by oxotremorine (0.75 mg/kg) but not by thioridazine or clozapine (16 mg/kg).

These results are discussed with regard to the mode of action of neuroleptic drugs in producing anti‐psychotic effects and drug‐induced Parkinsonism.
[3H]‐CLONIDINE BINDING TO α‐ADRENOCEPTORS IN MEMBRANES PREPARED FROM REGIONS OF GUINEA‐PIG KIDNEY: ALTERATION BY MONOVALENT AND DIVALENT CATIONS
Authors: SUMMERS R.J.
Published: May 2015

[3H]‐clonidine binds reversibly to membranes prepared from regions of guinea‐pig kidney.

Higher levels of binding were obtained in the membranes prepared from renal cortex (2.15 ± 0.27 pmol/g wet wt.) than renal medulla (0.53 ± 0.07 pmol/g wet wt.) or papilla (0.14 ± 0.06 pmol/g wet wt.; n = 4).

Scatchard analysis performed by addition of unlabelled clonidine (1 to 30 pmol) gave figures for the dissociation constant (Kd) for the binding of [3H]‐clonidine to renal cortical membranes of 9.0 ± 0.8 nm and Bmax of 21.6 ± 1.7 pmol/g wet wt. (n = 4). Hill plots of these data gave gradients close to unity, indicating a lack of co‐operative site interactions.

The monovalent cations, sodium and potassium, and the divalent cation, calcium, produced concentration‐dependent decreases in [3H]‐clonidine binding to membranes prepared from renal cortex, the EC50s being respectively 25 mm, 37 mm and 23 mm.

At low concentrations the divalent cations, magnesium (1 mm) and manganese (0.1 mm), produced enhancement of [3H]‐clonidine binding. At higher concentrations (> 10 mm) both divalent cations inhibited binding.

Scatchard analysis of [3H]‐clonidine binding performed in the presence of sodium (100 mm), magnesium (1 mm) or manganese (0.1 mm) revealed that the alterations in binding are primarily due to changes in apparent affinity rather than a change in the number of binding sites. Sodium (100 mm) produced a change in the Kd from 7.0 ± 0.4 nm (n = 8) to 42.3 ± 27.5 nm (n = 3), whereas magnesium (1 mm) decreased the Kd to 6.0 ± 0.9 nm and manganese (0.1 mm) to 4.0 ± 1.0 nm (n = 3).

The results indicate that [3H]‐clonidine labels a binding site that has properties resembling an α2‐adrenoceptor, located in the renal cortex. The changes produced by the addition of monovalent and divalent cations are entirely due to changes in the apparent affinity of [3H]‐clonidine binding.
EVIDENCE FOR THE METABOLIC ACTIVATION OF NON‐STEROIDAL ANTIOESTROGENS: A STUDY OF STRUCTURE‐ACTIVITY RELATIONSHIPS
Authors: ALLEN KAREN E. , CLARK E.R. , JORDAN V.C.
Published: May 2015

The oestrogenic and antioestrogenic activities of tamoxifen and monohydroxytamoxifen have been compared with those of para‐methoxy, ‐methyl, ‐fluoro, and ‐chloro tamoxifen in the 3 day immature rat uterine weight test.

The oestrogenic activity of mestranol, a steroid with low oestrogen receptor binding affinity which is believed to be demethylated to ethinyl oestradiol before exerting its effects, was less potent than ethinyl oestradiol when assayed in the 3 day immature rat uterine weight test. Similarly, para‐methoxytamoxifen was less active than monohydroxytamoxifen in oestrogenic and antioestrogenic tests.

The introduction of a para‐methoxy group into tamoxifen did not affect oestrogenic or antioestrogenic activity.

All the derivatives of tamoxifen were partial oestrogen agonists when compared with oestradiol benzoate in the 3 d immature rat uterine weight test. All test compounds inhibited the uterotrophic activity of oestradiol benzoate (0.16 μg daily) in a dose‐related manner. The order of potency was: monohydroxytamoxifen > tamoxifen ≡ methoxytamoxifen > p‐fluoro ≡ p‐chloro ≡ p‐methyltamoxifen.

Tamoxifen was approximately equiactive with its p‐methyl, p‐fluoro and p‐chloro derivatives in the ability to inhibit [3H]‐oestradiol binding to rat uterine oestrogen receptors in vitro.

Tamoxifen was approximately equiactive with its p‐methyl and p‐fluoro derivatives in the ability to inhibit vaginal cornification of ovariectomized rats upon intravaginal administration with oestradiol (3.2 ng total dose).

Since tamoxifen in vivo was more active as a partial oestrogen agonist and antagonist than the para substituted fluoro, chloro and methyl derivatives that cannot undergo metabolic hydroxylation to monohydroxytamoxifen, whereas the antioestrogenic activity of the compounds upon local application in the vaginal cornification test was equivalent as was their ability to inhibit [3H]‐oestradiol‐17 β binding to the oestrogen receptor in vitro, it is suggested that at low doses; i.e. over the range of the partial agonist dose‐response curve, the biological activity of tamoxifen is the net result of the activities of the parent compound and its metabolites.

The results demonstrate that metabolic activation of non‐steroidal antioestrogens is only an advantage and not a requirement for antioestrogenic activity.
INTERACTION OF SELECTIVE α‐ADRENOCEPTOR AGONISTS AND ANTAGONISTS WITH HUMAN AND RABBIT BLOOD PLATELETS
Authors: GRANT JACQUELINE A. , SCRUTTON MICHAEL C.
Published: May 2015

The selectivity of α‐adrenoceptors mediating the pro‐aggregatory response of human and rabbit platelets to adrenaline and the conditions required to permit expression of an aggregatory response to partial agonists at these α‐adrenoceptors have been studied.

Yohimbine causes effective blockade of the pro‐aggregatory responses whereas indoramin and prazosin are ineffective.

The clonidine analogue, UK‐14304, is nearly as effective as adrenaline in inducing an aggregatory response in human platelets and a pro‐aggregatory response in rabbit platelets. Cross‐tachyphylaxis between adrenaline and UK‐14304 has been demonstrated.

Clonidine is a weak agonist for the pro‐aggregatory response of rabbit platelets and in some donors for the aggregatory response of human platelets.

Methoxamine induces a pro‐aggregatory response in human platelets which is blocked by indoramin or prazosin but not by yohimbine. No such response to methoxamine is observed in rabbit platelets.

The divalent cation ionophore, A‐23187, induces an aggregatory response to clonidine (in platelets from a non‐responsive donor), phenylephrine and methoxamine in human platelets and to adrenaline, UK‐14304 and clonidine in rabbit platelets. A secretory response to clonidine is also induced by A‐23187 in human platelets.

The adenylate cyclase inhibitor, SQ‐22536, is ineffective in either inducing a response to the α‐agonists or potentiating the effect of A‐23187.

The aggregatory responses to adrenaline and UK‐14304 in rabbit platelets and to clonidine in human and rabbit platelets, which can be induced by A‐23187, are blocked by yohimbine but not by prazosin or indoramin.

From these studies we conclude that the pro‐aggregatory responses of human and rabbit platelets to adrenaline are mediated primarily by α2‐adrenoceptors. The presence of α1‐adrenoceptors on human platelets is confirmed but these receptors do not appear to be present on rabbit platelets. The conditions required for expression of an aggregatory response to partial agonists at the human and rabbit platelet α‐adrenoceptors implicate an increase in cytosolic Ca2+ concentration as a key event in stimulus‐response coupling but do not indicate such a role for depression of cyclic adenosine‐3′,5′‐monophosphate concentration.
A MODEL OF IRRITANT‐INDUCED BRONCHOCONSTRICTION IN THE SPONTANEOUSLY BREATHING GUINEA‐PIG
Authors: ALLOTT C.P. , EVANS D.P. , MARSHALL P.W.
Published: May 2015

Inhalation of an aqueous aerosol of citric acid caused bronchoconstriction in anaesthetized guinea‐pigs which was abolished by bilateral vagal section.

Conscious guinea‐pigs developed slow, laboured breathing within 90 s of exposure to citric acid aerosol. The onset of this pattern of breathing was delayed by prior aerosol administration of atropine, ipratropium bromide, isoprenaline and tetracaine.

The data suggest that exposure of guinea‐pigs to citric acid may be a useful model of reflex bronchoconstriction.
INHIBITION OF MONOAMINE OXIDASE BY FURAZOLIDONE IN THE CHICKEN AND THE INFLUENCE OF THE ALIMENTARY FLORA THEREON
Authors: ALI B.H. , BARTLET A.L.
Published: May 2015

The addition of furazolidone to the feed at the therapeutic level (0.04% w/w, 10 days) inhibited monoamine oxidase (MAO) activity by 47 to 72% in chicken duodenal mucosa, heart and brain, but in the liver the enzyme activity was unaffected by the treatment.

Furazolidone (200 mg/kg) administered by crop tube inhibited MAO activities in duodenal mucosa, liver, heart and brain.

Furazolidone (200 mg/kg) injected intramuscularly did not inhibit MAO activity in the chicken.

Pretreatment of the chickens with intramuscular neomycin did not antagonize the inhibition of MAO activity produced by furazolidone (200 mg/kg, crop tube).

Pretreatment with neomycin by crop tube to suppress the alimentary flora significantly reduced the effect of furazolidone on MAO activity, suggesting that the drug was transformed by the alimentary flora to an active metabolite which subsequently inhibited MAO activity in other organs.

Furazolidone in the feed (0.04% w/w, 10 days) or administered by crop tube (200 mg/kg) had no effect on the activity of aminopyrine demethylase in chicken liver.

The activity of aspartate transaminase in plasma was unaffected by the addition of furazolidone to the feed (0.04% w/w, 10 days).
A COMPARISON OF THE EFFECTS OF PANCURONIUM BROMIDE AND ITS MONOQUATERNARY ANALOGUE, ORG NC 45, ON AUTONOMIC AND SOMATIC NEUROTRANSMISSION IN THE RAT
Authors: DOCHERTY J.R. , McGRATH J.C.
Published: May 2015

Potentiation by pancuronium of the effects of adrenergic nerve stimulation, previously shown in cardiovascular tissues, was also found in rat anococcygeus and vas deferens, in vitro or in vivo.

In the pithed rat, in the presence of pancuronium, pre‐junctional α‐adrenoceptor‐mediated feedback inhibition of cardiac sympathetic transmission was uncovered at relatively low stimulation frequencies by phentolamine or yohimbine.

The effects of pancuronium and its mono‐quaternary analogue Org NC 45 on autonomic and somatic neuromuscular transmission were compared, in the pithed rat. Org NC 45 was less potent than pancuronium at blocking somatic neuromuscular transmission by a factor of 2.1, at blocking cardiac, parasympathetic transmission by a factor of 538 and at potentiating sympathetic transmission by a factor of 33.
EFFECTS OF SOME S‐ALKYLTHIOURONIUMS AND RELATED COMPOUNDS ON THE OSMOTIC FRAGILITY AND THE MEMBRANE EXPANSION OF HUMAN ERYTHROCYTES
Authors: BERESFORD ROSEMARY A. , FASTIER F.N.
Published: May 2015

Changes in the osmotic fragility and critical haemolytic volume of human erythrocytes produced by S‐n‐decylthiouronium (S‐10) and related compounds have been studied.

S‐10 had a biphasic action on osmotic fragility, protecting erythrocytes against lysis in low concentrations but producing lysis in a concentration of 1 mm or higher.

Some lower homologues of S‐10 also protected erythrocytes against osmotic lysis, the degree of protection depending on the length of the alkyl chain.

Critical haemolytic volume was increased by anthihaemolytic concentrations of procaine and chlorpromazine but not by antihaemolytic concentrations of S‐10 and related amidines.

It is concluded that S‐10 and its near homologues penetrate and stabilize erythrocyte membranes, potency increasing with the number of methylene groups in the side‐chain up to about ten. The stabilization produced by S‐10 apparently differs from that produced by many other lipid‐soluble depressant drugs. It may be related to a drug‐induced change in the ionic permeability of the membrane.
BINDING OF [3H]‐MUSCIMOL, A POTENT γ‐AMINOBUTYRIC ACID RECEPTOR AGONIST, TO MEMBRANES OF THE BOVINE RETINA
Authors: OSBORNE NEVILLE N.
Published: May 2015

The binding of [3H]‐muscimol, a potent γ‐aminobutyric acid (GABA) receptor agonist, to crude membrane preparations of bovine retina was studied, using a filtration method to isolate membranebound ligand.

Specific binding was found to be saturable and occurred at two binding sites with affinity constants of 4.3 nm and 38.2 nm.

Binding was sodium‐independent, enhanced by both freezing and Triton X‐100 treatment but abolished with sodium laurylsulphate.

The binding sites demonstrated a high degree of pharmacological specificity, GABA being a potent displacer of [3H]‐muscimol.

A higher degree of [3H]‐muscimol binding was associated with subcellular fractions enriched with photoreceptor synaptosomes rather than with fractions enriched with conventional synaptosomes.
Diabetes quality of care at a university community in Beirut
Authors: Lakkis Najla A. , Mahmassani Dina M. , Hamadeh Ghassan N.
Published: May 2015

Rationale, aims and objectives

To assess the quality of diabetes mellitus (DM) care provided by a group of family doctors in Beirut.

Methods

An observational study, conducted at the American University of Beirut Medical Center–Family Medicine Clinics (AUBMC–FMC), examined the electronic health records (EHRs) of the beneficiaries of the Health Insurance Plan at the American University of Beirut (AUB–HIP) who were older than 20 years (n = 9469) in 2009. The eligible population included patients with DM (n = 701). Several provider/patient‐directed interventions were introduced in the late 2000s, including a comprehensive EHRs system with point‐of‐care computer reminders, a provider financial incentive based on an annual performance appraisal ranked against that of the US Healthcare Effectiveness Data and Information Set (HEDIS) Comprehensive Diabetes Care indicators, as well as periodic up‐to‐date training.

Results

Optimal control for HbA1c, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglycerides and blood pressure were found in 58.6%, 51.0%, 22.4%, 53.3% and 60.2% of the population, respectively. 64.1% and 70.0% received screening for diabetic nephropathy and a dilated eye examination, respectively. When benchmarked against the HEDIS Comprehensive Diabetes Care indicators, the AUB–HIP's quality of care was 13% higher than the average of all plans in the United States. Screening for nephropathy, however, did not reach the above benchmark.

Conclusions

Benchmarking served as an important tool in evaluating the current DM care offered and in detecting gaps, yet interventions are recommended for further improvement.
Semilunar Coronally Advanced Flap with or without Low Level Laser Therapy in Treatment of Human Maxillary Multiple Adjacent Facial Gingival Recessions: A Clinical Study
Authors: Singh Neelesh , Uppoor Ashita , Naik Dilip
Published: May 2015

Purpose

Semilunar coronally advanced flap (SCAF) and its modifications or adjuncts have been proposed in the literature for root coverage. Low level laser therapy (LLLT) has been shown to enhance wound healing. The aim of this split‐mouth randomized controlled clinical trial was to assess the effects of LLLT application with respect to root coverage after SCAF procedure for the treatment of human maxillary multiple adjacent facial gingival recessions.

Materials and Methods

Ten subjects with bilateral multiple adjacent maxillary facial gingival recession defects (Miller I and II) were included in this study (20 in test, 20 in control group). A diode laser (810 nm) at 0.3 watts was applied to test sites during and 1 week after surgery for 10 seconds. Comparisons of the surgical sites were made with clinical measurements.

Results

Statistically significant differences were observed between test and control sites in the change in gingival recession depth, gingival recession width, clinical attachment level, and width of the keratinized tissue measurements after 6 months (p = 0.003, p = 0.001, p = 0.006, and p =< 0.001, respectively). The test group presented significantly greater complete root coverage (N = 18/20, 90%) compared with the control group (N = 6/20, 30%) at 6 months post‐operatively.

Conclusion

Within the confines of this study, the results depicted that a Low Level Laser Technique application may enhance the predictability of SCAF procedure. Further long‐term studies with more sample sizes are needed for a stronger evidence base.

Clinical Significance

Gingival recessions are commonly encountered in dentistry and pose an esthetic concern. Minimal gingival recessions can be treated by a Semilunar Coronally Advanced Flap (SCAF), but the predictability and stability of the outcomes are quiet questionable. In the present report, a Low Level Laser Technique (LLLT) application adjunct to SCAF depicted a significant improvement in the predictability and stability of root coverage outcomes (for a period of 6 months) compared with as achieved by SCAF alone. From this report, it can be stated that LLLT may be effectively used in a day to day practice for enhancing the root coverage outcomes of SCAF.
The pharmacokinetics of pimobendan enantiomers after oral and intravenous administration of racemate pimobendan formulations in healthy dogs
Authors: Bell E. T. , Devi J. L. , Chiu S. , Zahra P. , Whittem T.
Published: May 2015

Pimobendan is a benzimidazole‐pyridazinone derivative, marketed as a racemic mixture for the management of canine heart failure. Pharmacokinetics of the enantiomers of pimobendan and its oral bioavailability have not been described in dogs. The aim of this study was to describe pharmacokinetics of three formulations of pimobendan in healthy dogs: the licensed capsule product, and novel liquid and intravenous formulations. A three‐period, nested randomized two‐treatment crossover design was used. Pimobendan was administered p.o. at 0.25 and i.v. at 0.125 mg/kg. Blood and plasma samples were analysed by liquid chromatography–mass spectrometry. Noncompartmental modelling was used to describe the pharmacokinetics. Parameters were compared between formulations using a general linear model. Bioequivalence of the oral formulations was tested using CI90 for AUC(0–∞) and Cmax. Bioavailability of pimobendan after oral dosing was 70%. Liquid and capsule formulations were bioequivalent only for AUC. The positive enantiomer of pimobendan (PE) had a larger volume of distribution than the negative enantiomer (NE) (281 ± 48 vs. 215 ± 68 mL/kg; P = 0.003) and a shorter half‐life (21.7 vs. 29.9 min; P = 0.004). The NE was distributed more quickly than the PE into blood cells. Enantiomers of pimobendan have differing absorption, distribution and elimination. The pharmacokinetics of pimobendan in healthy dogs was described.
Pharmacokinetics of cefuroxime after intravenous, intramuscular, and subcutaneous administration to dogs
Authors: Albarellos G. A. , Montoya L. , Lorenzini P. M. , Passini S. M. , Lupi M. P. , Landoni M. F.
Published: May 2015

Cefuroxime pharmacokinetic profile was investigated in 6 Beagle dogs after single intravenous, intramuscular, and subcutaneous administration at a dosage of 20 mg/kg. Blood samples were withdrawn at predetermined times over a 12‐h period. Cefuroxime plasma concentrations were determined by HPLC. Data were analyzed by compartmental analysis. Peak plasma concentration (Cmax), time‐to‐peak plasma concentration (Tmax), and bioavailability for the intramuscular and subcutaneous administration were (mean ± SD) 22.99 ± 7.87 μg/mL, 0.43 ± 0.20 h, and 79.70 ± 14.43% and 15.37 ± 3.07 μg/mL, 0.99 ± 0.10 h, and 77.22 ± 21.41%, respectively. Elimination half‐lives and mean residence time for the intravenous, intramuscular, and subcutaneous administration were 1.12 ± 0.19 h and 1.49 ± 0.21 h; 1.13 ± 0.13 and 1.79 ± 0.24 h; and 1.04 ± 0.23 h and 2.21 ± 0.23 h, respectively. Significant differences were found between routes for Ka, MAT, Cmax, Tmax, t½(a), and MRT. T > MIC = 50%, considering a MIC of 1 μg/mL, was 11 h for intravenous and intramuscular administration and 12 h for the subcutaneous route. When a MIC of 4 μg/mL is considered, T > MIC = 50% for intramuscular and subcutaneous administration was estimated in 8 h.