bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy1
Authors: Sotgiu S. , Pugliatti M. , Sanna A. , Sotgiu A. , Castiglia P. , Solinas G. , Dolei A. , Serra C. , Bonetti B. , Rosati G.
Published: March 2003

Several lines of evidence indicate a genetic contribution to multiple sclerosis (MS) both in terms of predisposition to the disease and of immunological mechanisms which are known to play crucial roles in MS pathogenesis. The presence of high‐ and low‐risk areas for MS in neighbouring regions supports the theory that MS predisposition is influenced by a complex interaction of genetic and environmental factors. Therefore, the use of genetically homogeneous and geographically isolated populations becomes an increasing requirement to reduce biasing biological variables. Sardinians fulfil these conditions well because of their different phylogeny from Europeans and the unique selective pressures which shaped their genome. Sardinians display amongst the highest MS prevalence rates world‐wide and increasing MS incidence rates over time. Also, MS in Sardinia is linked to distinct human leucocyte antigen (HLA) alleles and associated to different patterns of cytokine production from lymphoid cells of different HLA subtypes. In this context, recent findings and future perspectives on the peculiarities of Sardinian MS concerning genetic, immunological and epidemiological aspects are presented. So far, our results indicate that variations at the level of territorial distribution and HLA‐association are present which render MS heterogeneous even in this ethnically homogeneous population.
Cerebral vasospasm and ischaemic infarction in clipped and coiled intracranial aneurysm patients
Authors: Hohlrieder M. , Spiegel M. , Hinterhoelzl J. , Engelhardt K. , Pfausler B. , Kampfl A. , Ulmer H. , Waldenberger P. , Mohsenipour I. , Schmutzhard E.
Published: March 2003

The influence of the treatment modalities (clipping/coiling) on the incidence of vasospasm and ischaemic infarction in aneurysm patients is still judged controversially. The purpose of this study was to analyse and compare retrospectively cerebral vasospasm and ischaemic infarction, as well as neurological deficits and outcome within a large population of clipped and coiled patients with ruptured and unruptured aneurysms. Within a 2‐year period, a total of 144 interventions (53 clipping/91 coiling) entered the study. Daily bilateral transcranial Doppler sonographic monitoring was performed to observe vasospasm development. All cerebral computed tomography (cCT) and magnetic resonance imaging (MRI) scans were reviewed with respect to occurrence and localization of ischaemic infarctions. Focal neurological deficits were recorded and clinical outcome was evaluated using the Glasgow Outcome Scale. Statistical analysis included the use of multivariate logistic regression models to find determinants of vasospasm, ischaemic infarction and neurological deficits. Altogether, vasospasm was detected after 77 (53.5%) interventions, 61.8% in females (P < 0.01). Clipped patients significantly more often exhibited vasospasms (69.8 vs. 44.0%, P < 0.005) and were treated 1 week longer at the intensive care unit (P < 0.005). Seventy‐seven patients (53.5%) developed ischaemic infarctions, 62.3% after clipping and 48.4% after coiling (P > 0.05). In the multivariate analysis, aneurysm‐rupture was the strongest predictor for vasospasm and vasospasm was the strongest predictor for infarction. Neurological deficits at discharge (46.5%) were independent of treatment modality, the same applied for the mean Glasgow Outcome Scores. There was no significant difference in mortality between surgical and endovascular treatment (9.4 vs. 12.1%). Whilst the vasospasm incidence was significantly higher after surgical treatment, ischaemic infarctions were only slightly more frequent. The incidence of neurological deficits and clinical outcome was similar in both treatment groups.
Cognitive impairment in community‐dwelling older Nigerians: clinical correlates and stability of diagnosis
Authors: Baiyewu O. , Unverzagt F. W. , Ogunniyi A. , Hall K. S. , Gureje O. , Gao S. , Lane K. A. , Hendrie H. C.
Published: March 2003

To determine correlates and outcome of cognitive impairment without dementia in community‐dwelling elderly Nigerians. A total of 2487 community residents aged 65 years and over were screened using the Community Screening Interview for Dementia. A subset of 423 individuals received diagnostic clinical evaluation. Participants were diagnosed normal, demented, or cognitive impairment no dementia (CIND). Follow‐up clinical diagnostic evaluation was conducted on CIND subjects approximately 2 years later. One hundred and fifty‐two persons were diagnosed CIND. Eighty‐seven CIND subjects were seen at follow‐up assessment, 14 (16.1%) had converted to dementia, 22 (25.3%) reverted to normal, and 51 (58.6%) remained CIND. No baseline factors predicted later development of dementia amongst the CIND subjects. CIND subjects who reverted to normal tended to be male and to have higher baseline cognitive scores. Apolipoprotein status was not related to diagnosis at follow‐up. CIND is common in community‐dwelling Nigerians. Although the outcome is variable, it does represent a high‐risk group for subsequent dementia.
Cerebral effects of hyperbaric oxygen breathing: a CBF SPECT study on professional divers
Authors: Di Piero V. , Cappagli M. , Pastena L. , Faralli F. , Mainardi G. , Di Stani F. , Bruti G. , Coli A. , Lenzi G. L. , Gagliardi R.
Published: March 2003

We investigated the effects on cerebral blood flow (CBF) of pure oxygen breathing exposure during dives in a group of professional divers, in both the normobaric (NBO) and the hyperbaric oxygen (HBO) breathing conditions. Using single photon emission computerized tomography (SPECT) and Tc‐99m hexamethylpropylenamine oxime (HM‐PAO), we studied 10 young divers and six normal volunteers. Divers were studied by SPECT in the NBO and HBO conditions, in two different sessions. The HBO state was obtained in a hyperbaric chamber at 2.8 ATA for 15 min. By ANOVA, we did not observe any significant difference in CBF distribution between controls and divers in both NBO and HBO conditions. By individual analysis, divers showed a decreased CBF in a total of 33 regions of interest (ROIs) during NBO and 46 ROIs during HBO with respect to control values. In particular, two divers showed a remarkable increase in the number of hypoperfused ROIs during HBO (+7 and +5 ROIs, respectively). Pure oxygen breathing exposure in young divers is associated with a patchy distribution of brain areas of hypoperfusion. This phenomenon is more pronounced in the HBO state than in the NBO state. Further studies on CBF are needed to help identify divers potentially prone to harmful oxygen effects.
Natural killer cell proliferation and circulating cytokines in patients with bilateral basal ganglia calcification
Authors: Morishima T. , Morita M. , Kato T. , Hoshino Y. , Kimura H.
Published: March 2003

Ten adult patients with symmetrical calcifications in the bilateral basal ganglia (diagnosed as physiological calcifications) were analyzed for lymphocyte subsets and cytokines. Increased number of natural killer (NK) cells were identified in the peripheral blood of seven patients by lymphocyte subset analysis. Tumor necrosis factor‐α was detected in the sera of five patients and interferon‐γ was detected in one patient. In summary, NK cell propagation and circulating cytokines, particularly tumor necrosis factor‐α, may be involved in the etiology of basal ganglia calcification.
Subacute rhombencephalitis optica responsive to intravenous immunoglobulins
Authors: Živković S. A. , Heyman R. , Pless M.
Published: March 2003

A 53‐year‐old man presented with optic neuritis, followed within 10 weeks by a subacute progression of weakness, ataxia, and multiple cranial nerve palsies. Cranial magnetic resonance imaging demonstrated multiple T2‐hyperintense lesions extending from the ponto‐medullary junction to the thalamus and internal capsule. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein content. A brain biopsy revealed inflammatory changes. After a month long period of inexorable worsening, the patient was treated with intravenous immunoglobulins (2 g/kg). He responded to treatment, and recovered over the subsequent 3 months. The patient's response to treatment suggests that intravenous immunoglobulins should be considered in patients with inflammatory brain disorders.
EMG myokymia as a cause of ptosis in hypothyroidism
Authors: Lo Y. L. , Ho S. C. , Koh L. K. , Khoo D. H.
Published: March 2003

Ptosis is known to be associated with thyroid disorders. We describe two biochemically corrected hypothyroid patients presenting with isolated bilateral ptosis. EMG of the orbicularis oculi showed continuous grouped motor unit potentials. In the absence of obvious aetiology, it is hypothesised that focal demyelination of terminal branches to the orbicularis oculi may play a role in the generation of the discharges.
Surgical therapy for Parkinson's disease
Authors: Olanow C. W.
Published: March 2003

Surgical therapies for Parkinson's disease (PD) are now being performed with increasing frequency due to the limitations of conventional dopaminergic therapies, improvements in operative procedures, and increased information on the organization of the basal ganglia in normal and pathologic conditions. Ablation procedures have now been largely replaced with deep brain stimulation, which permits benefits to be obtained without the need to make a destructive brain lesion. Several studies now demonstrate the value of stimulating the subthalamic nucleus or the globus pallidus pars interna in patients with advanced PD. Nonetheless, there are limitations associated with these procedures and benefits do not exceed those obtained with levodopa, albeit with reduced motor complications. Fetal transplantation remains an experimental procedure that has shown limited benefits in a double‐blind trial and is complicated by persistent dyskinesia. Stem cell, trophic factor, and gene therapy approaches are promising and are currently under intensive investigation.
Brain pH in Migraine: An In Vivo Phosphorus-31 Magnetic Resonance Spectroscopy Study
Authors: Welch K M A , Levine Steven R , D'Andrea Giovanni , Helpern J A
Published: March 2003

The intracellular pH (pHi) of cerebral cortex was measured in migraine patients by use of in vivo phosphorus-31 NMR spectroscopy. No changes in pHi were measured during a migraine attack. The long-standing concept that the headache of migraine is due to cerebral vaso-dilatation induced by prodromal vasospasm-induced ischemic acidosis is not substantiated.
The Nociceptive Flexion Reflex as a Tool for Exploring Pain Control Systems in Headache and Other Pain Syndromes
Authors: Sandrini Giorgio , Arrigo Andrea , Bono Giorgio , Nappi Giuseppe
Published: March 2003

The authors review the neural pathways mediating nociceptive flexion reflexes, the method for analyzing these reflexes in human beings, and available data on their modulation by supraspinal, opioid as well as serotonergic systems. They present results of studies of the biceps femoris flexion reflex (RIII) in pain syndromes and various types of headache. Nociceptive flexor reflexes appear to be interesting for studying the pathophysiology of head pain mechanisms and possibly for evaluating analgesic treatment.
Changes in Platelet Membrane Fluidity of Migraine Patients
Authors: Cotrim Maria Dulce , Ribeiro Carlos Alberto Fontes , Macedo Tice dos Reis Anastácio de
Published: March 2003

Platelet membrane fluidity was measured in migraine patients, with and without aura, using the fluorescent probe TMA-DPH (1–[4–(trimethylammonium) phenyl]-6–hexa-1,3,5–triene). Polarization values for TMA-DPH were significantly higher in the platelet membranes of migraine patients (with or without aura) than in those of healthy subjects. These findings signify decreased membrane fluidity and may explain some modifications in receptors, carriers or enzymes described in platelets of migraine patients.
A Review of Hormonal Findings in Cluster Headache. Evidence for Hypothalamic Involvement
Authors: Leone Massimo , Bussone Gennaro
Published: March 2003

The cause of cluster headache remains to be determined. The involvement of peripheral neurovascular structures can explain the pain and autonomic signs of a cluster attack, but not its rhythmicity. The central theory of cluster headache attributes the cyclic recurrence to involvement of the hypothalamus. To evaluate hypothalamic dysfunction a number of hormone studies have been carried out on cluster headache patients. Alterations in plasma melatonin, cortisol, testosterone, gonadotrophins, prolactin, growth hormone and thyrotropin have been documented, some only in the cluster period but others in the remission phase of the illness. We believe that the hormonal abnormalities in cluster headache support disorders of hypothalamic function.
Autonomic Nervous System and Neuroendocrine Changes in Patients with Idiopathic Trigeminal Neuralgia
Authors: Strittmatter M , Grauer MT , Fischer C , Hamann G , Hoffmann KH , Blaes F , Schimrigk K
Published: March 2003

To investigate sympathetic nervous system and neuroendocrine changes in idiopathic trigeminal neuralgia, we determined the plasma level of the catecholamines norepinephrine and epinephrine, as well as cortisol and ACTH in 16 patients (55.38.3 years) with trigeminal neuralgia at four different times during the day (7.00, 13.00, 17.00 and 23.00). Morning and evening values of plasma norepinephrine as well as the daily mean value (dmv) were significantly higher ( p<0.01) in patients with trigeminal neuralgia than in an age- and gender-matched control group. Moreover, morning, afternoon and dmv epinephrine values were also significantly elevated. The dmv norepinephrine levels correlated with the intensity of the attacks ( r=0.68, p<0.01), the frequency of the attacks ( r=0.75, p<0.01) and the duration of the disease ( r=0.78, p<0.01). In addition to elevated catecholamines, trigeminal neuralgia patients also demonstrated significantly increased morning, evening and daily mean values of plasma cortisol. Thus, patients with trigeminal pain have an increased sympathetic nervous system activity for an extended period of time without a direct link to pain attacks, which suggests that the sympathetic nervous system itself is at least co-activated in trigeminal neuralgia and perhaps plays a role in the induction and maintenance of trigeminal pain. The neuroendocrine changes are similar to cluster headache and point to a central dysregulation of the hypothalamic-pituitary-adrenal axis, possibly due to the cyclic phenomena in idiopathic trigeminal neuralgia.
Tender Points Are Not Sites of Ongoing Inflammation - In Vivo Evidence in Patients with Chronic Tension-Type Headache
Authors: Ashina M , Stallknecht B , Bendtsen L , Pedersen JF , Schifter S , Galbo H , Olesen J
Published: March 2003

Increased muscle tenderness is the most prominent finding in patients with tension-type headache, and it has recently been shown that muscle blood flow is diminished in response to static exercise in tender points in these patients. Although tenderness has been ascribed to local inflammation and release of inflammatory mediators, the interstitial concentration of inflammatory mediators has not previously been studied in tender muscles of patients with tension-type headache. The aim of the present study was to investigate in vivo concentrations of prostaglandin E2 (PGE2), adenosine 5'-triphosphate (ATP), glutamate, bradykinin and other metabolites in a tender point of patients with chronic tension-type headache, in the resting state as well as in response to static exercise, and to compare findings with measurements in a matched non-tender point of healthy controls. We recruited 16 patients with chronic tension-type headache and 17 healthy control subjects. Two microdialysis catheters were inserted into the trapezius muscle and dialysates were collected at rest, 15 and 30 min after start of static exercise (10% of maximal force) and 15 and 30 min after end of exercise. All samples were coded and analysed blindly. There was no difference in resting concentration of any inflammatory mediators or metabolites between tender patients and non-tender controls ( P > 0.05). We also found no difference in change in interstitial concentration of ATP, PGE2, glutamate, glucose, pyruvate and urea from baseline to exercise and post-exercise periods between patients and controls ( P > 0.05). The present study provides in vivo evidence of normal interstitial levels of inflammatory mediators and metabolites in tender trapezius muscle in patients with chronic tension-type headache during both rest and static exercise. Thus, our data suggest that tender points in these patients are not sites of ongoing inflammation.
Tectonic control over large‐scale diffuse degassing in eastern Sicily (Italy)
Authors: De Gregorio S. , Diliberto I. S. , Giammanco S. , Gurrieri S. , Valenza M.
Published: March 2003

Eastern Sicily (southern Italy) is characterised by the presence of many natural gas emissions (mofettes, mud volcanoes). These gases are mostly carbon dioxide and methane, with minor amounts of helium, hydrogen, carbon monoxide and hydrocarbons. In this study, the extent and orientation of soil gas anomalies (He and CO2) were investigated on a wide area (approximately 110 km2) located just SW of Mt. Etna. From a structural point of view, this area lays on a typical foredeep–foreland system that marks the boundary between the southern part of the Eurasian plate and the northern part of the African plate in the central Mediterranean. No tectonic structure was revealed in this area by surface geological surveys. Very high soil emissions were found, and their spatial pattern reveals the existence of some active faults all directed about N50°E. This direction coincides with that of two major fault systems that cut eastern Sicily and are evident, respectively, NE and SW of the study area. Soil gas data suggest that these fault systems are the expression of a single continuous structural line which is probably responsible for the past and present magma uprise in eastern Sicily. Isotopic values of carbon of CO2 suggest a minor contribution of organic carbon. Moreover, in the highest degassing sites the isotopic values of He found in association with CO2 (He abundance = 11–70 p.p.m.; R/Ra between 6.0 and 6.2) suggest that both gases are mantle derived. The extent of the areas affected by high gas emissions and the amounts of deep CO2 emitted in the investigated area (several hundred tonnes per day) may provide additional supporting evidence of a mantle upwelling taking place beneath this region.
Nutritional information and consumer behaviour – their relationship to nutritional balance. A study conducted in Berlin
Authors: Ulbricht Gottfried J. F.
Published: March 2003

A sample of 503 randomly selected adults were asked about sources of nutritional information and food habits. In addition, participants were also asked to maintain a food record for three consecutive days. One hundred and forty‐nine participants completed both the questionnaire and 3‐day diary. Results indicate that of the 13 sources of nutritional information, friends and relatives were most frequently quoted, while scientific publications as well as advertising on packaging material were most rarely quoted. However, scientific publications and reports of the ‘Commodity Test Foundation’ (Stiftung Warentest) enjoy the greatest confidence. In addition, people relying on scientific publications show healthier eating habits. Only one of the 18 items in the nutritional behaviour tested (‘I try to keep to the rules of healthy nutrition’) shows a highly significant positive correlation with healthy nutrition. There is a negative correlation between acceptability and healthy nutrition. The main conclusions indicate that nutritional consciousness and dietary habits of both adoles‐cents and adults, as well as the health value of food, must be improved.
The renowned cactus moth, Cactoblastis cactorum: its natural history and threat to native Opuntia floras in Mexico and the United States of America
Authors: Zimmermann H. G. , Moran V. C. , Hoffmann J. H.
Published: March 2003

Abstract. The cactus moth, Cactoblastis cactorum (Berg) (Phycitidae) is native to South America. It was released as a biological control agent against alien Opuntia‐cacti in Australia in the 1920s, then in southern Africa, and latterly on several islands, including those in the Caribbean. In 1989, the cactus moth was discovered in Florida, in the United States of America, where it is now threatening the survival of indigenous Opuntia species. In this paper we identify some of the attributes that have contributed to the success of C. cactorum as a weed biological control agent. Many of these same qualities account for the problems that C. cactorum has caused in Florida and predispose it as a major threat to the speciose, native Opuntia‐floras of Central and North America. An estimated 79 platyopuntia (prickly pear) species are at risk: 51 species endemic to Mexico; nine species endemic to the United States; and 19 species common to both countries. Many cultivated and wild Opuntia species, that are used in various ways, are also vulnerable to attack by C. cactorum, including at least 25 species in Mexico and three species in the United States, particularly the widely exploited and culturally important cultivars of O. ficus‐indica. Some control strategies are suggested that may minimize the risk and consequences of invasion by the cactus moth. The wider implications of this threat to the practice of weed biological control and to conservation are discussed.
Species richness of helminth parasites in Mexican amphibians and reptiles
Authors: Pérez‐Ponce de León Gerardo , García‐Prieto Luis , Razo‐Mendivil Ulises
Published: March 2003

Abstract.Amphibians and reptiles represent an important group of vertebrates in Mexico; on a global scale 10% of the biodiversity of these groups is found in the country, attaining extraordinarily high levels of endemism (60.7% and 53.7%, respectively). However, fewer than 20% of the known species of amphibians and reptiles in Mexico have been surveyed for helminths, so the inventory is far from complete. We assembled a data base that includes a total of 1246 records (entries) of which 460 correspond to helminths in amphibians and 786 to helminths in reptiles. In total, only 41 species of amphibians (14% of those occurring in Mexico) and only 118 species of reptiles (17% of those occurring in Mexico) have been studied for helminth parasites. From amphibians, 119 species of helminths belonging to 60 genera have been recorded, while 239 species of helminths representing 113 genera have been described from Mexican reptiles. One feature of the distribution of helminths of Mexican amphibians and reptiles is its asymmetry, as seen in representation of helminth groups, host groups and geographical range. However, such statistical asymmetry might be an artefact of sampling effort. Based on our data, we estimate that if all the herpetofauna of Mexico could be studied in the following years, approximately 827 additional species of helminths from amphibians and approximately 1403 from reptiles would be described.
Climate change and amphibian declines: is there a link?
Authors: Carey Cynthia , Alexander Michael A.
Published: March 2003

Abstract. Global climates have been changing, sometimes rapidly and dramatically, throughout the evolutionary history of amphibians. Therefore, existing amphibian species have been derived from those that have survived major climatic disturbances. Although recent global climate change has resulted in warming in many regions, temperatures in some areas to date have not changed measurably, or have even cooled. Declines of some amphibian populations have been correlated with climate events, but demonstrations of direct causal relationships need further research. Data are available indicating some indirect effect of climate change on the initiation of breeding activities of some amphibians that occur earlier than in previous springs, but the costs and benefits of these changes are just beginning to be investigated. Climate may also play an indirect role in facilitating epidemics of infectious disease. Regardless of the role that climate changes may have played in past and current amphibian declines, future shifts in climate, should they prove as dramatic as predicted, will certainly pose challenges for surviving amphibian populations and for successful recovery efforts of species that have suffered declines.
S15176 and S16950 interaction with Cyclosporin A antiproliferative effect on cultured human lymphocytes
Authors: Albengres Edith , Le Louët Hervé , D'Athis Philippe , Tillement Jean‐Paul
Published: March 2003

S15176 and S16950 are trimetazidine derivatives that antagonize more strongly than the parent drug mitochondrial toxicity, which leads to cellular hypoxia and nephrotoxicity in kidneys experimentally exposed to cyclosporin A. We have investigated whether every derivative might interact or not with the inhibitory effect of Cyclosporin A on the proliferation of cultured human lymphocytes. S15176 significantly increased the antilymphoproliferative effect of Cyclosporin A, whereas S15176 by itself neither displayed any antilymphoproliferative effect, nor did it induce any apoptotic process in cultured human lymphocytes. The effect of S16950 was not significant.
Effects of endothelin‐A receptor antagonism on bilateral renal function in renovascular hypertensive rats
Authors: Kassab Salah , Hamdy Hossam , AbdulGhaffar Tarik , Granger Joey P.
Published: March 2003

Recent studies indicated an enhanced expression of Endothelin (ET) in the kidney contralateral to the vascular clip in two‐kidney, one‐clip (2K‐1C) Goldblatt hypertension. We proposed that the enhanced intrarenal ET production might be responsible for altered haemodynamic and excretory capability of the unclipped kidney (UK) of 2K‐1C renovascular hypertensive rats. Therefore, we examined the changes in arterial pressure and split renal function in the clipped (CK) and UK simultaneously, in response to chronic administration of the selective ETA receptor blocker (A‐127722), given orally at a dose of 30 mg/kg/day for 3 weeks starting from the beginning of the 4th week of clipping. Systolic pressure averaged 177 ± 7 mmHg in control rats (n=15) and 164 ± 9 mmHg in treated rats (n=16) and the difference was not statistically different. Glomerular filtration rate (GFR), renal plasma flow (RPF) and renal vascular resistance (RVR) in the UK were not different between control and treated groups. Data were then analyzed by classifying rats as moderate hypertensives (MAP < 180 mmHg), and severe hypertensives (MAP > 180 mmHg). In the moderately hypertensive group, average MAP was 143 ± 5 mmHg and 138 ± 4 mmHg in control (n=9) and treated (n=10) groups, respectively. In the severely hypertensive group, average MAP was 192 ± 5 mmHg and 188 ± 5 mmHg in control (n=6) and treated (n=6) groups, respectively. GFR and RPF were significantly improved in the UK of only the severely hypertensives who received the antagonist. However, the ETA antagonist blunted the sodium loss in both CK and UK of severely hypertensive rats. We conclude that ETA receptors do not play a role in the progression of hypertension in 2K‐1C renovascular hypertensive rats. Yet, ETA receptors play an important role in altering renal hemodynamics of the unclipped kidneys in severe degrees of renovascular hypertension.
Binding of KRH‐594, an antagonist of the angiotensin II type 1 receptor, to cloned human and rat angiotensin II receptors
Authors: Inada Y. , Nakane* T. , Chiba S.
Published: March 2003

We studied the binding properties of KRH‐594, a new selective antagonist of angiotensin II (AII) type 1 (AT1) receptors, to rat liver membranes and to recombinant AT1 and AT2 receptors. Preincubation of rat liver membranes with KRH‐594 produced maximal inhibition of [125I]‐AII binding when the preincubation time was 1–2 h. Preincubation with KRH‐594 for 2 h decreased the Bmax value and increased the Kd value. For human AT1, human AT2, rat AT1A and rat AT1B receptors, the Ki values for KRH‐594 were 1.24, 9360, 0.67, and 1.02 nm, respectively. The rank order of Ki values for human AT1 receptors was KRH‐594 >> EXP3174 > candesartan=AII. The order of specificities for human AT1 and AT2 receptors was candesartan > EXP3174 > KRH‐594. Although a 2‐h preincubation of human AT2 receptors with KRH‐594 (30 µm) or CGP 42112 (a selective AT2 receptor antagonist; 0.3 nm) inhibited binding of [125I]‐AII, the suppression by KRH‐594 was not significant. These results indicate that KRH‐594 binds potently to AT1 receptors in an insurmountable manner, and that at a very high dose (30 µm) it may also bind to AT2 receptors, but in a surmountable manner.
Effect on cancer cell proliferation of palmitoylethanolamide, a fatty acid amide interacting with both the cannabinoid and vanilloid signalling systems
Authors: De Petrocellis Luciano , Bisogno Tiziana , Ligresti Alessia , Bifulco Maurizio , Melck Dominique , Di Marzo Vincenzo
Published: March 2003

Palmitoylethanolamide (PEA) is a bioactive fatty acid amide belonging to the class of N‐acyl‐ethanolamines (NAEs). This compound has been known since the 1950s for its anti‐inflammatory effects, but was re‐discovered only after the finding that another NAE, arachidonoyl‐ethanolamide (anandamide, AEA), could act as an endogenous ligand of cannabinoid receptors. Although a similar function for PEA has also been proposed, this compound does not activate the two cannabinoid receptor subtypes described to date. PEA and AEA are co‐synthesized by cells, and PEA might act as an ‘entourage’ compound for AEA, i.e. as an endogenous enhancer of AEA biological actions. Indeed, long‐term treatment of human breast cancer cells (HBCCs) with PEA downregulates the expression of the enzyme responsible for AEA degradation, the fatty acid amide hydrolase, thereby leading to an enhancement of AEA‐induced, and cannabinoid CB1 receptor‐mediated, cytostatic effect on HBCCs. AEA is also a full agonist for the receptors of another class of bioactive fatty acid amides, the N‐acyl‐vanillyl‐amines (e.g. capsaicin and olvanil). These sites of action are known as vanilloid receptors of type 1 (VR1). PEA enhances the VR1‐mediated effects of AEA and capsaicin on calcium influx into cells. These ‘entourage’ effects of PEA might be attributable to modulation of VR1 activity, and could underlie the enhancement by PEA, described here for the first time, of the antiproliferative effects of VR1 receptor agonists.
Influence of administration vehicles and drug formulations on the pharmacokinetic profile of lamotrigine in rats
Authors: Castel‐Branco M. M. , Figueiredo I. V. , Falcão A. C. , Macedo T. R. A. , Caramona M. M.
Published: March 2003

Given that administration vehicles and drug formulations can affect drug bioavailability, their influence on the pharmacokinetic profile of lamotrigine (LTG), a new‐generation anti‐epileptic drug, was studied in rats. Three different formulations administered intraperitoneally at a dose of 10 mg/kg were used: (1) LTG suspended in a 0.25% methylcelulose solution, (2) LTG dissolved in a 50% propylene glycol solution, and (3) LTG isethionate dissolved in distilled water. Plasma and brain homogenate levels were determined in order to evaluate vehicle‐dependent drug absorption. The results demonstrated rapid absorption of LTG when it was administered as an aqueous solution, in contrast to a slower and more erratic absorption after the injection of either the lipophilic solution or the suspension. A plasma peak was achieved 15 min post‐dose with the aqueous solution, with a brain peak being achieved 15 min later, while with the other formulations both plasma and brain homogenate peaks were reached 2 h after LTG administration. This study suggests that LTG isethionate dissolved in distilled water is the most suitable formulation for successful LTG pharmacokinetic studies in rats.
Assessment of fluid balance by measurement of skin tissue thickness during clinical anaesthesia
Authors: Klaus Stephan , Eichler Wolfgang , Heringlake Matthias , Schmucker Peter , Bahlmann Ludger
Published: March 2003

Study objective: To determine if measuring skin tissue thickness by a recently developed 10 MHz ultrasound scan may be used as a valuable parameter to guide fluid therapy and detect fluid shifts to the extravascular space during surgical procedures in addition to central venous pressure (CVP).

Study design: Prospective, clinical and observational study.

Setting: An operation theatre of the Ear Nose Throat (ENT) department of an university hospital.

Patients: Following approval by the local ethics committee 12 otherwise healthy male patients undergoing ENT surgery for oropharyngeal carcinoma were involved in this study. The patients stayed nil per os for 10 h before induction of anaesthesia.

Interventions/measurements: Crystalline fluids (Ringer's solution) were supplied at a constant rate of 10 ml kg–1 bw h–1. Patients were kept in the supine position during surgery, no further interventions were performed. Additional to routine monitoring, tissue thickness (TT) of proximal pre‐tibial skin and CVP were measured every 30 min, haematocrit was determined hourly for 5 h starting at t0.

Main results: Haematocrit constantly declined during the observation period, showing a significant difference in t0 after 120 min. The increase in TT was strongly correlated with intraoperative positive fluid balance (r=0·96), while the course of CVP did not reflect the amount of fluid application comparably.

Conclusions: Non‐invasive determinations of skin tissue thickness by the presented ultrasonic device appears to give additional information on fluid intake and distribution during clinical anaesthesia.
Do preceding vasoconstrictions influence the `inspiratory gasp test'?
Authors: Mueck‐Weymann M. , Rauh R.
Published: March 2003

Diabetic or other neuropathies can affect the autonomic innervations of vessels and heart. Using non‐invasive and inexpensive autonomic tests, one can detect autonomic neuropathy. One of these tests is the inspiratory gasp response (IGR). It appears as a short reduction of skin blood volume (SBV) following deep inspiration (DI). Unfortunately, because of a high degree of variability of the study results, the clinical merits of this test have been questioned. However, there remains vagueness about underlying mechanisms or pitfalls. The aim of the study was to identify preceding vasoconstrictor episodes as putative pitfalls in assessing IGR. With regard to the hypothesis that a preceding vasoconstrictor episode may affect the amplitude of the following one, we investigated SBV in fingertips of 25 healthy test subjects (14 females, 11 males; mean age 24 years), using the photoplethysmographic technique. After adaptation to environmental conditions the subjects were instructed to perform five DI in various time lags (90, 30, 20 and 180 s). We found that the shorter the time interval to a preceding IGR, the lower the amplitude of the following IGR. After an interval of 180 s, the amplitude increased again. We conclude that this newly observed phenomenon might explain the contradictory results of the IGR test found in some earlier studies. We suppose that reduced IGR may depend on alterations in peripheral norepinephrinergic transmission processes (e.g. emptying of norepinephrine reservoirs). In clinical studies it should be ruled out that a diagnostically assessed IGR is influenced by a preceding vasoconstrictor episode.
The quality of spirometric examinations in Finland: results from a national questionnaire survey
Authors: Piirilä Päivi , Pietinalho Anne , Loponen Minna , Naumanen Helga , Nurminen Markku , Siukola Aino , Korhonen Olli , Koskela Kaj , Sovijärvi Anssi
Published: March 2003

National treatment programmes for asthma and chronic obstructive pulmonary disease (COPD) have in the past few years increased the need for spirometry in Finland. The purpose of this study was to determine, by means of a national questionnaire survey, the quality and number of spirometric examinations performed in Finland in 1998, the year when the national COPD programme was initiated.

We estimated that 395 000–425 000 spirometric examinations were performed in Finland in 1998. The mean quality of spirometry was evaluated as moderate, and the quality index developed for this study indicated an average of scores of 67 (max 100), ranging between 43 and 88 in the whole country. The most common qualitative insufficiencies in spirometric examinations were found in preparation of the subject for the examination, performance of the examination, recognition of a successful spirometric curve and evaluation of reproducibility of the examination. Furthermore, the time reserved in the reports for performing the examination was often very short. However, in comparison with the previous questionnaire survey in Finland (in 1990), the quality of spirometry had markedly improved.
The validity of the Computer Science and Applications activity monitor for use in coronary artery disease patients during level walking
Authors: Ekelund Ulf , Tingström Pia , Kamwendo Kitty , Krantz Monica , Nylander Eva , Sjöström Michael , Bergdahl Björn
Published: March 2003

The principal aim of the present study was to examine the validity of the Computer Science and Applications (CSA) activity monitor during level walking in coronary artery disease (CAD) patients. As a secondary aim, we evaluated the usefulness of two previously published energy expenditure (EE) prediction equations. Thirty‐four subjects (29 men and five women), all with diagnosed CAD, volunteered to participate. Oxygen uptake (VO2) was measured by indirect calorimetry during walking on a motorized treadmill at three different speeds (3·2, 4·8 and 6·4 km h−1). Physical activity was measured simultaneously using the CSA activity monitor, secured directly to the skin on the lower back (i.e. lumbar vertebrae 4–5) with an elastic belt. The mean (±SD) activity counts were 1208 ± 429, 3258 ± 753 and 5351 ± 876 counts min−1, at the three speeds, respectively (P<0·001). Activity counts were significantly correlated to speed (r=0·92; P<0·001), VO2 (ml kg−1 min−1; r=0·87; P<0·001) and EE (kcal min−1; r=0·85, P<0·001). A stepwise linear regression analysis showed that activity counts and body weight together explained 75% of the variation in EE. Predicted EE from previously published equations differed significantly when used in this group of CAD patients. In conclusion, the CSA activity monitor is a valid instrument for assessing the intensity of physical activity during treadmill walking in CAD patients. Energy expenditure can be predicted from body weight and activity counts.
Ventilatory efficiency and rate of perceived exertion in obese and non‐obese children performing standardized exercise
Authors: Marinov B. , Kostianev S. , Turnovska T.
Published: March 2003

Sixty children, in the age span 6–17 years originally divided into two groups, matched by age, sex and height – 30 obese subjects [15 girls/15 boys; body mass index (BMI)=27·4 ± 4·5 m kg−2; ideal body weight (IBW) range=122–185%] and 30 controls (BMI=18·8 ± 2·7 m kg−2) performed incremental treadmill exercise test. Perceived exertion was assessed by means of Category‐Ratio Borg scale. The duration of the exercise for the children in the obesity group was significantly shorter than controls (P=0·010) but obese children have greater absolute values for oxygen uptake (VO2peak ml min−1=1907 ± 671 versus 1495 ± 562; P=0·013) and ventilatory variables (VE, VT), which adjusted for body mass decrease significantly (VO2/kg ml min−1 kg−1=29·2 ± 3·8 versus 33·6 ± 3·5; P<0·001). Among the various methods for ‘normalizing’ absolute values of VO2peak for body size, dividing it by body surface area (BSA) yielded the best results (VO2/BSA ml min−1 m−2=43·5 ± 4·6 versus 44·7 ± 5·6; P=0·335). The ventilatory efficiency determined either as a slope of VE versus VCO2 or as a simple ratio at anaerobic threshold did not differ between obese and non‐obese children in the incremental and recovery periods of exercise. There was a negative correlation of VE/VCO2 slope with age and anthropometric parameters. Obese children rated perceived exertion significantly higher than controls despite the standard workload (Borg score=6·2 ± 1·2 versus 5·2 ± 1·1; P=0·001). In conclusion, the absolute metabolic cost of exercise is higher in the obesity group compared with the control subjects. Both groups have similar ventilatory efficiency but an increased awareness of fatigue that furthermore limits their physical capacity.
Cardiovascular effects of ophthalmic 0·5% timolol aqueous solution and 0·1% timolol hydrogel
Authors: Niño J. , Tahvanainen K. , Uusitalo H. , Turjanmaa V. , Hutri‐Kähönen N. , Kaila T. , Ropo A. , Kuusela T. , Kähönen M.
Published: March 2003

The objective of this randomized, double‐masked, cross‐over study was to compare the cardiovascular effects of two glaucoma formulations, ophthalmic 0·5% timolol aqueous solution and 0·1% timolol hydrogel. Twenty‐four young healthy subjects received for 2 weeks either twice daily 0·5% timolol solution or once daily 0·1% timolol hydrogel. Heart rate (HR), blood pressure, atrio‐ventricular conduction (PR interval), corrected QT time (QTc) and heart rate variability (HRV) were measured in supine position and during head‐up tilted position. The mean peak concentrations of timolol in plasma were significantly higher after administration of 0·5% aqueous solution than after 0·1% hydrogel. A 0·5% timolol aqueous solution decreased HR on average by 3 bpm in supine position and by 7 bpm in head‐up tilted position while no significant effects were observed with 0·1% timolol hydrogel. During tilt test HR was significantly lower after administration of timolol aqueous solution than after timolol hydrogel (mean ± SD, 77 ± 11 bpm versus 86 ± 13 bpm, P < 0·05). Timolol aqueous solution slightly decreased QTc during tilt (5·9 ± 5·6 ms, P < 0·01). During tilt tests, timolol aqueous solution slightly increased atrio‐ventricular conduction (7·2 ms, P = 0·02). No significant differences were found in HRV. These results indicate that in healthy volunteers, ophthalmic 0·5% timolol aqueous solution produces more pronounced cardiac beta‐blocking effects than 0·1% timolol hydrogel.
The effect of equicaloric medium‐chain and long‐chain triglycerides on pancreas enzyme secretion
Authors: Symersky T. , Vu M. K. , Frölich M. , Biemond I. , Masclee A. A. M.
Published: March 2003

It has been shown previously that medium chain triglycerides (MCT) do not affect gallbladder emptying and cholecystokinin (CCK) release. The effect of MCT on exocrine pancreas secretion in humans is unknown. We have compared the effect of enteral administration of MCT versus long chain triglycerides (LCT) on exocrine pancreatic secretion. Eight healthy subjects (three female, five male; mean age 22 ± 1·9 years) participated in two experiments, performed in random order. Duodenal contents, obtained by aspiration, were used to calculated the output of pancreatic enzymes and bilirubin. An equicaloric amount of either MCT or LCT (2 kcal min−1) oil was continuously administered in the proximal jejunum for 2 h. Gallbladder volume was measured by ultrasonography and blood samples were drawn for determination of CCK. The experiments consisted of 1 h basal secretion, 2 h of continuous oil administration and 1 h poststimulation. During the LCT feeding the pancreatic enzyme secretion, bilirubin output, gallbladder emptying and CCK release increased significantly (P<0·05) over basal levels. MCT had no effect on pancreatic enzyme secretion nor gallbladder emptying or CCK release. We conclude that enteral administration of MCT in the proximal jejunum does not stimulate exocrine pancreatic secretion nor gallbladder contraction or CCK release, in contrast to an equicaloric amount of LCT.
Decreased actin solubility observed during ATP‐depletion is mimicked by severing agents but not depolymerizing agents in isolated and cultured proximal tubular cells
Authors: White Peter , Gu Luo , Chen Jing
Published: March 2003

The microvilli of the apical membrane of proximal tubule (PT) cells are supported by the underlying actin cytoskeleton. Ischaemic or anoxic ATP‐depletion leads to the disruption of the actin cytoskeleton, resulting in microvillar retraction and loss of membrane polarity. Using isolated PT cells, we have previously demonstrated that actin filaments (F‐actin) are likely severed during ATP‐depletion. A sequential extraction protocol revealed a decrease in actin solubility, resulting in the sequestration of a distinct F‐actin pool with the insoluble cellular complex in ATP‐depleted PT cells. We demonstrate here that decreased actin solubility is not only a reliable end‐marker of ATP‐depletion induced injury in freshly isolated PT cells, but also serves as a biochemical marker in the cultured proximal tubular cell line LLC‐PK1. In the present studies, we also investigated specific actin‐binding drugs to determine if they mimic the effects observed during energy depletion. Jasplakinolide (JP), a compound which binds F‐actin and prevents depolymerization, did not effect actin solubility during ATP‐depletion. Furthermore, swinholide A (SA), an F‐actin severing agent, resulted in decreased actin solubility, mimicking the effects of ATP‐depletion. Interestingly, latrunculin A (LA), an agent which depolymerizes F‐actin, did not reduce actin solubiltity, but rather resulted in an increase in digitonin‐soluble actin. Taken collectively, our results support previous work and suggest that disruption of the actin cytoskeleton during ATP‐depletion is mediated by F‐actin severing/fragmentation and not depolymerization. The differential effects of F‐actin disrupting agents and the consistencies observed in both models of ischaemic injury will provide a basis for a more detailed understanding of the pathological events of PT‐cell dysfunction.
PET imaging using a triple‐head gamma camera
Authors: Kuikka J. T. , Sohlberg A. , Husso‐Saastamoinen M.
Published: March 2003

Interest in clinical fluorodeoxyglucose (FDG) imaging with multiple‐head gamma cameras is growing. To improve sensitivity, triple‐head coincidence imaging has been proposed. We report our initial experiences with a triple‐head coincidence gamma camera with 19 mm sodium iodide crystal thickness. Several positron emission tomography‐image quality parameters were evaluated using a Carlson and line source phantom. The system sensitivity with two‐dimensional axial shields was 830 cps kBq−1 ml−1 and maximum noise equivalent count rate 1900 cps for an 18F‐activity of 50 MBq. The imaging resolution was in central axial 7·0 mm and in central transaxial 7·6 mm, respectively. The average scatter fraction in scattered media was 29%. Clinical brain, heart and whole body images studies with [18F]FDG were acquired and they show good correlation with the phantom image quality. As a conclusion, triple‐head coincidence gamma camera provides relatively high‐count rate imaging with good contrast and resolution.