bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytochrome P‐450‐product Complexes Produced by Amphetamine Derivatives: A Comparative Study with Isolated Liver Microsomes and Hepatocytes
Authors: Hirata Masaharu , Högberg Johan , Thor Hjördis , Orrenius Sten 
Published: July 2010

Abstract1. Incubation of liver microsomes from phenobarbital‐treated rats with N‐hydroxyamphetamine or norbenzphetamine in the presence of NADPH and molecular oxygen gave rise to the formation of a cytochrome P‐450‐product complex characterized by maximal light absorption at 456 nm. Complex formation was more rapid and extensive with N‐hydroxyamphetamine than with norbenzphetamine as substrate.2. When incubation was performed with hepatocytes isolated from phenobarbital‐treated rats, the formation of the cytochrome P‐450‐product complex was less rapid as well as less extensive. In fact, with some cell preparations incubation with norbenzphetamine failed to produce any spectrophoto metrically observable cytochrome P‐450‐product complex.3. Incubation of the hepatocytes with norbenzphetamine caused a decrease in the cellular level of reduced glutathione (GSH) suggesting consumption of GSH during the metabolism of the drug. Moreover, GSH and certain other sulfhydryl compounds inhibited norbenzphetamine‐induced cytochrome P‐450‐product complex formation in the liver microsomal fraction. The extent of inhibition by GSH was moderately enhanced by the addition to the microsomes of a purified preparation of glutathione‐S‐epoxide transferase.4. When higher concentrations of norbenzphetamine (> 1 mM), or certain other lipophilic amines, were added to suspensions of hepatocytes, there was a rapid lysis of the cells which was preceeded by a dramatic decrease in the cellular ATP level. This effect could be correlated to uncoupling of phosphorylation from respiration in experiments on isolated rat liver mitochondria.5. It is suggested that further metabolism via a GSH‐linked pathway may act by decreasing the concentration of cytochrome P‐450‐binding norbenzphetamine metabolite(s) in the hepatocyte, thus inhibiting cytochrome P‐450‐product complex formation from this drugin vivo.
Is Moderate Ethanol Consumption Teratogenic in the Rat?
Authors: Øisund Jan Fredrik , Fjorden Ann‐Elin , Mørland Jørg 
Published: July 2010

AbstractFemale Wistar rats were given ethanol in their drinking fluid to cover 20–25% of the total calories consumed for 3–4 weeks prior to, during and also after pregnancy in some experiments. Soya oil was substituted for ethanol isocalorically in the control groups.Apart from a statistically significant reduction in litter size based on the number of apparent normal foetuses at intrauterine examination, no significant changes in reproductive performance could be recorded after ethanol treatment. In the offspring, examined up to 24 days of age, the body and some viscera weights were statistically significantly higher at some stages from 2 to 14 days. The general trend, however, showed that there were no significant differences in body, brain, liver, kidney, and heart muscle weights between control and ethanol offspring measured in rats between 0 and 24 days of age. Two gross malformations were recorded among 321 pups of ethanol treated mothers, whereas no malformations were found in 444 control pups. It was concluded that moderate ethanol consumption by rat mothers for 3–4 weeks before and during pregnancy as well as during the suckling period, had no serious effects on their reproductive performance and the development of their offspring measured by the parameters used in the present investigation.
Cholinergic Mechanisms in the Rat Detrusor Muscle
Authors: Elmér Mats 
Published: July 2010

AbstractThe motor response of the urinary bladder to nerve stimulation is resistant to atropine, and it has been proposed that the nerves are non‐cholinergic, but are possibly purinergic. In this review evidence is presented suggesting a cholinergic transmission in the rat detrusor muscle, part of the receptors being inaccessible to atropine.The rat bladder receives postganglionic cholinergic fibres not only from the pelvic but also from the hypogastric nerves, some fibres passing outside the pelvic ganglia and some relaying distal to them. There is a functional overlap between the right and the left pelvic nerve, but the contractile response to stimulation of the hypogastric nerves is added to the pelvic nerve response with no functional overlap or antagonism.
Calcium Entry Blockade and Excitation Contraction Coupling in the Cardiovascular System (with an attempt of pharmacological classification)
Authors: Godfraind Theophile 
Published: July 2010

Abstract:Calcium may be considered as the final intracellular messenger of excitation‐contraction coupling. In this report the main mechanisms involved in the cellular regulation of calcium movements are reviewed. Most of the pharmacological agents actually available for therapy interfere with the processes responsible for increase in cytoplasmic activator calcium.Study of the relation between contraction and calcium movements shows that blockade of calcium entry may cause inhibition of contraction. This has allowed to illustrate some of the characteristics of calcium channels in smooth muscle. Potential‐operated channels are activated by changes in membrane potential, that can be evoked by K‐rich solutions. They are completely blocked by calcium antagonistic dihydropyridines and diphenylpiperazines. This blockade shows (time‐)use‐dependence. They are opened by calcium agonistic dihydropyridines. Receptor‐operated channels are activated by the interaction of an agonist with its receptors; they are incompletely blocked by calcium antagonistic dihydropyridines and diphenylpiperazines.Endothelium appears to modulate the response of the adjacent smooth muscle to vasoconstrictors. This may be accounted for by modulation of calcium metabolism, both at the level of membrane channels and of intracellular stores. As a consequence, endothelium modulates the action of calcium entry blockers.Study of isolated human tissues illustrates difference in drug sensitivity between cardiac and smooth muscle. Human isolated coronary arteries are sensitive to nifedipine concentrations found in the blood of patients receiving therapeutic regimen. These concentrations do not alter the contractility of the isolated human myocardium.Differences between drugs may be explained assuming that they may interact with one of the states (closed, open, inactivated) of the Ca channels. This also helps the understanding of tissue selectivity of some compounds.A pharmacological classification of calcium entry blockers may be proposed. This classification is a rationale to differentiate between the various clinical indications of drugs affecting calcium movements.
The Relationship between Macro– and Microcirculation Clinical Aspects
Authors: Fagrell Bengt 
Published: July 2010

Abstract: A large number of methods are today available for the clinical evaluation of the arterial blood supply to an extremity or part of an extremity. However, these methods are not sensitive enough for determining the nutritional status of a tissue in the extremity affected by vascular disorders. This is especially true for the skin where most of the blood is used for thermoregulation and only a small fraction goes through the nutritional capillaries. Blood may enter the subpapillary vascular network through AV‐shunts and bypass the nutritional skin capillaries. Therefore microcirculatory methods has to be used in order to be able to evaluate the nutritional status of a certain skin area.One of the clinically most useful methods for this purpose is vital capillary microscopy. By classifying structural changes of the nutritional capillaries in an area susceptible to ischemia, the risk of necrosis can be evaluated. Marked discrepancies between the total circulation of the are and the nutritional status of the tissue can be seen especially in patients with peripheral vascular disorders and/or diabetes. The total circulation may be markedly reduced but necrosis does not occur until the nutritional circulation of the ischemic skin area is completely abolished for a certain period of time. On the other hand it is sometimes seen in clinical practise that ischemic skin necrosis may develop in a region with rather good macrocirculation. These findings are of utmost importance when the effect of a certain treatment should be evaluated. The effect has to be studied directly in the target organ, and that is the nutritional vascular bed of the ischemic area.
Calcium Channel Blockade and Renal Function
Authors: Odar–Cederlöf Ingegerd 
Published: July 2010

Abstract: Since calcium channel blocking agents were introduced into the treatment of hypertension their influence on renal function has become an important issue.In animal experiments calcium channel blocking agents have been shown to increase renal blood flow and glomerular filtration rate and to augment urine flow and electrolyte excretion.In human acute studies the administration of calcium channel blocking agents have elicited similar renal hemodynamic and diuretic effects. Clinical studies on the renal effects of long‐term treatment are however still lacking.Studies on the effect on renin release have given divergent results. In acute experiments renin release is increased by calcium channel blocking agents. En long‐term treatment, however, no change in peripheral plasma levels of renin has been demonstrated.The influence of decreased renal function on the pharmacokinetics of calcium channel blocking agents has been studied in patients with renal disease. For verapamil the volume of distribution is smaller in uremic patients than in normals and both metabolic and renal clearances are decreased. For nifedipine, on the other hand, similar plasma levels, plasma half life and total plasma clearance are found in uremic patients and normal subjects.
ON THE MUSCARINIC RECEPTORS IN THE URINARY BLADDER AND THE PUTATIVE SUBCLASSIFICATION OF MUSCARINIC RECEPTORS
Authors: Nilvebrant Lisbeth 
Published: July 2010

Abstract:The muscarinic cholinergic receptors in the urinary bladders of man, guinea pig, rat and rabbit were studied by means of a receptor binding technique, with L‐quinuclidinyl [phenyl4‐3H]benzilate, (‐)3H‐QNB, as radioligand. The potential role of the receptors in the supersensitivity of the rat bladder to muscarinic agonists, following parasympathetic denervation, hypertrophy and urinary diversion, was also investigated. In addition, the binding of various unlabelled antimuscarinic drugs in the guinea pig bladder was compared to that in other tissues in order to study the putative muscarinic receptor subtypes, commonly referred to as M1and M2. According to this classification the putative M1receptors prevail in discrete areas of the brain, whereas the M2‐receptors predominate in peripheral tissues, such as the exocrine glands and smooth muscles.The receptor density (but not the qualitative properties of the receptors) in the bladder differed between the species. The affinities of various antimuscarinic drugs were virtually identical in the guinea pig and human bladders. In both species, the binding data were found to correlate with functionalin vitrodata. In the rat bladder, the receptor density was increased after denervation but decreased, below control values, when the denervation was combined with urinary diversion. A decrease was also found after urinary diversion of innervated bladders, whereas the receptor density was unaffected by hypertrophy. These results suggest that the receptors are not involved in the development of supersensitivity and that the receptor levels may be influenced by the functional state of the bladder.Binding studies with classical muscarinic antagonists indicated that the receptors in the guinea pig bladder are indistinguishable from those in the ileum, heart, parotid gland and cerebral cortex. However, four drugs ‐ namely, oxybutynin, dicyclomine, benzhexol and pirenzepine had a much higher affinity for the receptors in the parotid gland and cortex than for those in the other tissues. Moreover, dicyclomine and benzhexol, like pirenzepine, seemed in the cortex to distinguish between two classes of sites exhibiting high and low affinity. The high affinity sites could be selectively labelled with3H‐benzhexol. The ability of oxybutynin, dicyclomine, benzhexol and pirenzepine to discriminate between the receptors in the parotid gland and those in smooth muscle provides further evidence that the M1/M2concept is inaccurate. The present data indicate that there may be three classes of muscarinic antagonist binding sites.
Clinical pharmacological aspects on nitrate tolerance
Authors: Beennann Björn 
Published: July 2010

Abstract:There is strong evidence that nitrate tolerance develops rapidly during repeated administration in the systemic resistance vascular bed and that there exists cross tolerance between different nitrates.There are divergent opinions on how tolerance in the systemic capacitance and the pulmonary vascular bed develops. This may be explained by real differences in tolerance development in ischemic heart disease and congestive heart failure but also by the use of several different preparations of nitrates in the studies performed.Available data on the pharmacokinetics of nitrates present a complex picture with highly variable bioavailability, clearance and apparent volume of distribution both inter‐ and intraindividually. It is suggested that nitrate tolerance should be studied in very homogenous groups of patients with well defined hemodynamics. The nitrate used should have a very short half‐life allowing for simulation of various modes of administration by intravenous infusion.
Microcirculatory methods for evaluating the effect of vasoactive drugs in clinical practice
Authors: Fagrell Bengt 
Published: July 2010

Abstract:Microcirculatory methods have to be used in order to be able to evaluate the effect of vasoactive drugs in ischemic skin areas. During the past two decades several new such techniques for studying the microcirculation in man have been developed. These techniques have shown to be of great value for evaluating drug effects in patients with disturbed peripheral circulation. One such method is the non‐invasive Laser Doppler technique. It measures both the nutritional and the non‐nutritional thermoregulatory vascular bed of the skin. The data achieved are only semiquantative, but the method has been shown to be clinically very useful for studying the dynamics of total skin microcirculation in a specific area.In order to be able to study directly what happens in the nutritional capillaries microscopical methods have to be used. Two such techniques are available in clinical practice. By an ordinary light microscope the capillaries can be directly visualized. A specific classification system can be used to evaluate the degree of ischemic damage to an area. The effect of different kinds of therapeutic procedures for improving the microcirculation in an ischemic area can be easily evaluated. By the combination of a light microscope and a sensitive TV‐camera the blood flow in single skin capillaries can be measured at a magnification of 250–1000 times. This method is well suited for testing the immediate effects of vasoactive substances on the nutritional skin circulation both in healthy subjects and in patients with different kinds of cardiovascular diseases.
Tolerance to organic nitroesters in experimental animals. An assessment of in vitro and in vivo investigations
Authors: Axelsson Krister L , Ahlner Johan , Ljusegren Marie Ekstam 
Published: July 2010

Abstract:This paper will present a short survey of the literature dealing with nitrate tolerance in experimental animals.Tolerance towards organic nitroesters has been experimentally established in animal models bothin vivoandin vitro.However the dose of drug used to provoke tolerance has invariably been very high, which makes it difficult to apply experiences from animal experiments to the clinical setting.Several different hypothesis has been put forward in order to explain the mechanism of tolerance. Today, most evidence seem to point towards an altered metabolism of cGMP as a possible cause of tolerance. Cyclic GMP is the second messenger suggested to mediate the vasodilatory effect of organic nitroesters. The proposed role of critical tissue sulfhydryl groups in mediating the smooth muscle relaxant effect of nitroglycerin (NTG) have made experiments concerning reversal and prevention of tolerance to center on the use of various sulfhydryl reactive compounds. The results of these experiments are as yet ambigous.Several studies show the existence of cross tolerance between NTG and various other vasodilatory organic nitroesters. In contrast no cross tolerance between NTG and chemically unrelated vasodilator drugs has been observed.The endogenous vasodilators acetylcholine and atrial natriuretic factor are known to induce cGMP increases. In view of this, their effect on NTG‐tolerant bovine mesenteric arteries was investigated. However no cross‐tolerance appears to exist underin vitroconditions.
Excessive iodine intake during pregnancy in Somali refugees
Authors: Kassim Ismail A.R. , Ruth Laird J. , Creeke Paul I. , Gnat Danielle , Abdalla Fathia , Seal Andrew J. 
Published: July 2010

AbstractIodine deficiency and excess are both associated with adverse health consequences, with fetuses, children and pregnant women being most vulnerable to the devastating effects of severe deficiency. It is often assumed that the iodine status of a population if displaced or in a remote or emergency situation is low. However, there is little evidence available to support this assumption, especially among long‐term food‐aid‐dependent pregnant women. An effectiveness trial of a prenatal multiple‐micronutrient supplement that contained 150 µg day−1iodine was conducted in two refugee camps in the North Eastern Province of Kenya in 2002. Urinary iodine concentration (UIC) was measured in a subsample of pregnant women attending antenatal care in Dagahaley (control camp) (n = 74) and Ifo (intervention camp) (n = 63). There was no significant difference in median UIC between the two camps (P = 0.118). The combined median UIC was 730 µg L−1(interquartile range, 780) (5.77 µmol L−1) and exceeded the upper safe limit of 500 µg L−1(3.95 µmol L−1) for pregnant women (P < 0.001), indicating excessive iodine intake. About 20% of the study subjects had ‘more than adequate’ urinary iodine, while over 71% had excessive UIC. Salt iodine content varied between 5.1 and 80.1 ppm in the five market salt samples analysed. In conclusion, excessive iodine intake was evident in the Dadaab refugee camps. Further research needs to be conducted to investigate the source of excess iodine, to determine the measures needed to address excessive iodine intake and to reconsider the World Health Organization/World Food Programme/United Nations Children's Fund guidance on supplementation of vulnerable groups in emergencies.
Comparison of nurse practitioner job core competency expectations of nurse managers, nurse practitioners, and physicians in Taiwan
Authors: Fang Li‐Fen , Tung Heng‐Hsin 
Published: July 2010

Abstract Purpose: The purpose of this study was to compare expectations of nurse practitioner (NP) job competencies among physicians, nurse managers, and NPs. Data Sources: A quantitative survey was designed using the Analytic Hierarchy Process to determine the essential NP job competencies based on a checklist of 38 daily activities of NPs, which were recorded for a 10‐day period. Using purposive sampling, a demographic data tool and a Nurse Practitioner Job Competency Questionnaire were completed by 56 participants from 13 hospitals in Taiwan, for which they prioritized and assigned percentage weights for NP competencies. A qualitative open‐ended interview was undertaken to establish the meaning of the hierarchy outcomes that had been obtained. Conclusions: NPs face the pressure of whether medical staff and nurses agree with NPs' perceptions of their role, which can result in conflicts between nurses and doctors. Taiwanese NPs are still seen as assistants to doctors and, as such, the benefits of the creation of this new field of nursing are not being fully utilized. Implications for Practice: NPs should be aware of discrepancies among health professionals as to their role, make efforts to communicate what their competencies include to avoid conflicts, and use their abilities effectively.
Saliva crystallisation as a means of determining optimal mating time in bitches
Authors: Pardo‐Carmona B. , Moyano M. R. , Fernández‐Palacios R. , Pérez‐Marín C.C. 
Published: July 2010

Objectives: To chart saliva crystallisation patterns throughout pro‐oestrus and oestrus in bitches, and to assess their reliability as a tool for optimising the timing of breeding.Methods: Six beagle bitches with normal reproductive activity were used. Saliva ferning patterns were established during pro‐oestrus and oestrus. Vaginal cytology, progesterone (P4) levels and behavioural signs were used to determine the optimum mating time. Receiver operating characteristic (ROC) analysis was performed.Results: Different ferning patterns were scored from 0 to 2. Although variations in saliva crystallisation were noted during the follicular phase of the oestrous cycle in bitches, the test did not prove accurate; test sensitivity was 40·6%, i.e. too low to reliably discriminate the fertile period, while specificity was 86·1%.ClinicalSignificance: This test could be used to complement other methods of determining the fertile period in bitches, but its potential capacity remains to be demonstrated.
Differential effects of TGF‐β and FGF‐2 on in vitro proliferation and migration of primate retinal endothelial and Müller cells
Authors: Romo Phillip , Madigan Michele C. , Provis Jan M. , Cullen Karen M. 
Published: July 2010

Abstract.Purpose:  During retinal development, the pattern of blood vessel formation depends upon the combined effects of proliferation and migration of endothelial cells, astrocytes and Müller cells. In this study, we investigated the potential for transforming growth factor‐β (TGF‐β) and fibroblast growth factor (FGF‐2) to influence this process by regulating proliferation and migration of retinal endothelial and macroglial cells.Methods:  We assessed the effects of exogenous TGF‐β and FGF‐2 on the proliferation and migration of cultured endothelial (RF/6A) and Müller cell (MIO‐M1) lines. Cell proliferation was measured using a MTT [3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) colorimetric assay over 72 hr. Cell migration was measured using a scratch‐wound assay over 72 hr.Results:  Transforming growth factor‐β inhibited the proliferation of endothelial and Müller cells and inhibited the migration of Müller cells, but not endothelial cells, compared to untreated controls. Conversely, FGF‐2 increased endothelial cell proliferation but inhibited endothelial cell migration. Fibroblast growth factor‐2 increased migration of Müller cells but had little effect on proliferation except at higher concentrations (20 ng/ml).Conclusion:  Taken together, these observations indicate that TGF‐β and FGF could work in concert to inhibit endothelial cell proliferation and migration, respectively; this may have implications for establishing and maintaining the avascular zone of primate fovea.