bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrathecal Treatment for Spasticity
Authors: Miles John
Published: April 2003

Although initially to be treated by oral spasmolytics, established spasticity is being increasingly recognised as needing direct pharmacotherapy to the spinal cord by the intrathecal route using drug delivery systems. Although the spasticity is mainly of spinal origin due to trauma or multiple sclerosis (M.S.), it can emanate from the brain as in cerebral palsy in children and require the same direct treatment. Drug delivery systems are now proven to be safe, clinically reliable, and cost effective and should be considered earlier in the disease process.
Regional Cerebral Blood Flow Changes in Patients with Intractable Obsessive Compulsive Disorders Treated by Limbic Leukotomy
Authors: Kim Moon-Chan , Lee Tae-Kyu , Son Byung-Chul , Choi Chang Rak , Lee Chul
Published: April 2003

The object of this study is to assess the changes in regional cerebral blood flow (rCBF) following stereotactic limbic leukotomy in patients with medically intractable Obsessive-Compulsive Disorder (OCD). Technetium-99-Hexa Methyl Propylene Amine Oxime (99mTc-HMPAO) Single Photon Emission Computed Tomography (SPECT) data obtained before and after limbic leukotomy were subjected to image fusion with MRI images. Eight samples were obtained from healthy voluteers. After localization of the ROI (Region Of Interest) in anatomical area, rCBF measurements were obtained by METLAB. The results of this study show a change of rCBF following limbic leukotomy in intractable OCD. Postoperative 99mTc-HMPAO SPECT findings implicate the medial frontal cortex, cingulate and striatum, which culd be linked to limbic leukotomy that blocks the functional connection of corticolimbic loop.
Protective Effect of Spinal Cord Stimulation on Experimental Early Cerebral Vasospasm
Authors: Visocchi M. , Di Rocco F. , Meglio M.
Published: April 2003

In this study we investigate the effects of cervical spinal cord stimulation (cSCS) on experimental ‘early spasm’ in rabbits as described in personal previous experience (Acta Neurochir 2001;143:177–185). Twenty-four adult red Burgundy rabbits wearing a cervical epidural electrode underwent cerebral blood flow (CBF) and functional monitoring of early basilar spasm before and during cSCS. CBF changes, as a consequence of cSCS, occurred in 20 control animals. No CBF changes, consistent with no basilar artery vasospasm, occurred after subarachnoid haemorrhage (SAH) up to the end of the experiments in all the stimulated animals. The role of reversible functional sympathectomy in mediating the effect of spinal cord stimulation on early spasm is discussed. cSCS is able to prevent ‘early spasm’ due to SAH in all the animals studied, independently from the occurrence and the sign of stimulation induced CBF variations.
Vasoactive Intestinal Polypeptide and Gastrin-Releasing Peptide Attenuate Hepatic Microvasculatory Disturbances following Intestinal Ischemia and Reperfusion
Authors: Leister Ingo , Mbachu Ebenzar M. , Post Stefan , Samel Stefan T. , Stojanovic Tomislav , Gutt Carsten N. , Becker Heinz , Markus Peter M.
Published: April 2003

Background/Aims: In addition to the primarily affected small bowel, intestinal ischemia and reperfusion (IIR) also leads to a marked decrease in hepatic microcirculation. The aim was to determine the potentially protective effect of the vasoactive hormones vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP) on hepatic microcirculation following IIR. Methods: Using a rat model, three animal groups were subjected to 40 min of intestinal ischemia, two of which were infused with either VIP or GRP (n = 12 each). Following reperfusion, hepatic intravital microscopy was performed. Portal venous perfusion, activities of serum glutamate pyruvate transaminase and alkaline phosphatase, mucosal injury in the small intestine and the expression of antioxidant enzymes glutathione peroxidase, copper-zinc-superoxide dismutase (Cu-Zn-SOD), glutathione reductase and catalase (CAT) in the liver were investigated. Results: Infusion of either VIP or GRP improved hepatic microcirculation and bile flow when compared with the untreated IIR group. VIP and GRP increased portal venous blood flow during reperfusion. VIP reduced the extent of mucosal damage resulting from IIR. GRP caused a decrease in expression of CAT and Cu-Zn-SOD, whereas VIP simply reduced CAT expression. Conclusion: This study indicates that vasoactive hormones may attenuate intestinal and hepatic injuries and circulatory disturbances following IIR.
Nitric Oxide Releasing Aspirin Protects the Gastric Mucosa against Stress and Promotes Healing of Stress-Induced Gastric Mucosal Damage: Role of Heat Shock Protein 70
Authors: Konturek Peter C. , Brzozowski Tomasz , Ptak Agata , Kania Joanna , Kwiecień Sławomir , Hahn Eckhart G. , Konturek Stanisław J.
Published: April 2003

Background/Aim: Nitric oxide (NO) releasing nonsteroidal anti-inflammatory drugs do not cause gastric mucosal damage, despite inhibition of the cyclooxygenase activity to a similar extent as conventional nonsteroidal anti-inflammatory drugs that induce such damage. We compared the effects of native aspirin (ASA) with those of NO-releasing ASA (NO-ASA) on the development and healing of acute gastric lesions induced by water immersion and restraint stress (WRS) and the mucosal expression of heat shock protein 70 (HSP70). Methods: Wistar rats received: (1) vehicle; (2) ASA (40 mg/kg i.g), and (3) NO-ASA (2.5–40 mg/kg i.g.), followed 0.5 h later by 3.5 h of WRS with or without glyceryl trinitrate, the donor of NO, and carboxy-PTIO, a NO scavenger. Healing of WRS lesions was assessed 0–24 h after termination of WRS. Number of gastric lesions, gastric mucosal blood flow (GBF), malondialdehyde (MDA) content, and RT-PCR expression of HSP70 mRNA were determined. Results: WRS caused typical bleeding erosions that were aggravated by aspirin and this was accompanied by a fall in the GBF and a significant rise in the mucosal MDA concentrations. In contrast, NO-ASA, which raised significantly the luminal content of NOx, reduced number of WRS lesions and mucosal MDA levels while increasing significantly the GBF. These protective and hyperemic effects of NO-ASA against WRS lesions were mimicked by addition of glyceryl trinitrate to native ASA and significantly attenuated by carboxy-PTIO added to NO-ASA. HSP70 mRNA was significantly upregulated by WRS, and this was significantly attenuated by ASA, but not by NO-ASA. NO-ASA decreased significantly the MDA content and induced overexpression of HSP70 mRNA during healing of WRS lesions.Conclusion: NO-ASA exhibits mucosal protective and healing effects against WRS-induced gastric lesions due to the release of NO, which induces gastric hyperemia, and the attenuation of lipid peroxidation and counteracts the inhibition of HSP70 expression induced by native ASA.
Possible Modulatory Role of Nitric Oxide in Lung Toxicity Induced in Rats by Chronic Administration of Bleomycin
Authors: El-Khatib Aiman S.
Published: April 2003

Background: The present study was undertaken to evaluate whether stimulation or inhibition of nitric oxide (NO) synthesis could affect lung toxicity induced by chronic administration of bleomycin (BLM). L-arginine (ARG) and NG-nitro-L-arginine methyl ester (L-NAME) were employed as NO precursor and NO synthesis inhibitor, respectively. Methods: BLM was administered intraperitoneally to male Wistar rats at a dose of 15 mg/kg, 3 times a week, for a total period of 4 weeks. ARG (500 mg/kg/day) and L-NAME (100 mg/kg/day) were given in drinking water, the treatments commenced with BLM and continued up to the end of the experiment. Appropriate controls were performed. Results: BLM treatment resulted in a pronounced fall in the average body weight of animals, together with a rise in the lung weight/body weight ratio. In the lung tissue, elevated levels of hydroxyproline (HP) and lipid peroxides (LP) as well as decreased activity of angiotensin converting enzyme (ACE) further evidenced the toxicity. Pulmonary level of NO end products, nitrite and nitrate, tended to rise but did not reach a significant level. Glutathione (GSH) content and GSH-peroxidase activity measured in the lung remained unaltered. In animals given concurrent treatment of BLM and ARG, a remarkable rise in the pulmonary level of nitrite and nitrate was observed. Average body weight was still decreased when compared with the untreated control group, but the decrease was significantly less than that observed in the BLM group. In addition, ARG decreased the extent of BLM-induced elevations of lung HP and LP levels. Meanwhile, ARG failed to significantly affect the BLM-evoked decrease in pulmonary ACE activity and increase in lung weight/body weight ratio. In animals given simultaneous treatment of BLM and L-NAME, noticeable reductions in the pulmonary levels of nitrite/nitrate and GSH were detected. BLM-induced decrease in body weight and increase in lung weight/body weight ratio were accentuated by L-NAME co-treatment. Furthermore, administration of L-NAME led to more profound elevations in lung HP and LP levels, without affecting the decrease in pulmonary ACE activity elicited by BLM. Conclusion: In principle, the present findings indicate that the lung toxicity exerted by chronic administration of BLM is alleviated by ARG, but exacerbated by L-NAME supplementation. This could indicate a possible protective role of NO.
Activation of Human Mast Cells through Stem Cell Factor Receptor (KIT) Is Associated with Expression of bcl-2
Authors: Baghestanian Mehrdad , Jordan John-Hendrik , Kiener Hans P. , Bevec Dorian , Agis Hermine , Fritsch Gerhard , Müller Michael R. , Bankl Hans Christian , Schernthaner Gerit-Holger , Lechner Klaus , Valent Peter
Published: April 2003

Background: Mast cells (MCs) are multifunctional effector cells of the immune system. These cells originate from pluripotent hemopoietic progenitors. In contrast to basophils and other leukocytes, MCs exhibit a remarkably long life span (years) in vivo. Although a role for stem cell factor (SCF) and SCF receptor (KIT) in long-term survival of MCs has been proposed, the underlying biochemical mechanisms remain unknown. Materials and Methods:We have examined expression of ‘survival-related’ molecules of the bcl-2 family including bcl-2 and bcl-xL, in primary human MCs and the human MC line HMC-1. Primary MCs were isolated from dispersed lung tissue by cell sorting using an antibody against KIT. mRNA expression was analyzed by RT-PCR and Northern blotting. Results: As assessed by RT-PCR, purified unstimulated lung MCs (>98% pure) exhibited KIT- and bcl-xL mRNA, but did not express bcl-2 mRNA. However, exposure of lung MCS to SCF (100 ng/ml) for 8 h resulted in expression of bcl-2 mRNA. Corresponding results were obtained by immunocytochemistry. In fact, exposure of MC to SCF resulted in expression of the bcl-2 protein whereas unstimulated MCs displayed only the bcl-xL protein without expressing the bcl-2 protein. The human MC leukemia cell line HMC-1, which contains a mutated and intrinsically activated SCF receptor, showed constitutive expression of both bcl-2 and bcl-xL at the mRNA and protein level. Conclusion: Our data show that human MCs can express members of the bcl-2 family. It is hypothesized that bcl-xL plays a role in KIT-independent growth of MCs, whereas bcl-2 may be involved in KIT-dependent functions of MCs.
A High-Molecular-Weight Mite Antigen (HM1) Fraction Aggravates Airway Hyperresponsiveness of Allergic Mice to House Dusts and Whole Mite Cultures
Authors: Tategaki Airo , Kawamoto Seiji , Okuda Takahide , Aki Tsunehiro , Yasueda Hiroshi , Suzuki Osamu , Ono Kazuhisa , Shigeta Seiko
Published: April 2003

Background: The house dust mite Dermatophagoides farinae is the most common aeroallergen causing human allergic asthma. Previously, we demonstrated that a high-molecular-weight allergenic fraction (HM1), which was abundant in D. farinae extracts, induced a proliferative response of T cells from healthy donors. The induction was mediated through the activation of macrophages without MHC class II restriction. In this study, we investigate whether HM1 influences the development of airway inflammation in murine models of asthma. Methods: BALB/c mice were injected twice intraperitoneally with D. farinae fecal extract (Dff) at an interval of 5 days. They were exposed daily to aerosolized antigen (group 1: Dff, group 2: HM1, group 3: HM1-depleted Dff and group 4: PBS) for 10 days. The effect of HM1 on their airway inflammation was evaluated by measuring acetylcholine-induced airway hyperresponsiveness and inflammatory cell infiltration in lung tissue. Results: The inhalation of the whole fecal extract or the HM1 fraction induced airway hyperresponsiveness which was detectable after 24 h and was maintained for as long as 120 h. The inhalation of extract depleted of the HM1 fraction induced hyperresponsiveness measured at 24 h but this was not maintained for 120 h. Macrophage infiltration was significantly prolonged in mice inhaling the whole extract and the HM1 fraction compared to the HM1-depleted extract. Conclusion: The inhalation of the high-molecular-weight HM1 fraction of D. farinae prolonged airway hyperresponsiveness and macrophage inflammation in a mouse model of hypersensitivity. The results indicate that the HM1 fraction which can induce T cell proliferation through macrophage activation may play a role in the duration of airway responsiveness.
In vitro Human Plasma Leucine5-Enkephalin Degradation Is Inhibited by a Select Number of Drugs with the Phenothiazine Molecule in Their Chemical Structure
Authors: Mosnaim Aron D. , Puente Javier , Saavedra Rolando , Diamond Seymour , Wolf Marion E.
Published: April 2003

A number of drugs with the phenothiazine molecule in their chemical structure inhibit in a dose-dependent manner human plasmatic aminopeptidase leucine5-enkephalin (LEU) metabolism. Half-life peptide degradation was significantly increased by thioridazine > fluphenazine > As-1397 [10-(α-diethylaminopropionyl)phenothiazine] ≧ promethazine ≧ chlorpromazine (final drug conc. 10–4M); t1/2 (± SD) 21.2 ± 1.1, 19.6 ± 1.0, 17.2 ± 0.9, 17.1 ± 1.0, and 17.1 ± 1.1 min, respectively. Control and bacitracin (known aminopeptidase inhibitor) values were 11.8 ± 1.0 and 31.3 ± 1.7 min, respectively. These drugs significantly decreased (listed in the same order) LEU degradation initial velocity; Iv (± SD) 0.77 ± 0.2, 0.82 ± 0.2, 0.92 ± 0.3, 0.93 ± 0.2, 0.94 ± 0.3 pg LEU/min, respectively. Control and bacitracin 1.10 ± 0.3 and 0.20 ± 0.1 pg LEU/min, respectively. Values represent results from 5 samples, each obtained by pooling 6 individual plasmas (4 male and 2 female; n = 30 healthy, drug-free volunteers). However, neither the phenothiazines ethopropazine, methotrimeprazine, prochlorperazine and trifluoperazine nor the various commonly used heterocyclic antipsychotics tested, e.g., molindone, loxapine, clozapine, haloperidol, sulpiride and thiothixene inhibited plasma LEU degradation kinetics. Our results failed to show correlations between chemical structure, antipsychotic properties and ability to inhibit plasmatic aminopeptidase LEU degradation. Whereas, presence of the phenothiazine molecule appears to be necessary for enzyme inhibition, only five out of nine substituted phenothiazines tested exhibited this effect. Furthermore, there was a lack of correlation between phenothiazines antipsychotic properties and their capacity to inhibit aminopeptidase activity, a property shown by promethazine (antihistaminic) and As-1397 (selective butyrylcholinesterase inhibitor) but lacking in prochlorperazine and trifluoperazine. Our results provide information which could lead to the rational design of agents capable to modulate the bioavailability of enkephalin and other endogenous aminopeptidase-degraded peptides believed to be involved in the etiology and/or pathophysiology associated with various disease conditions. Whether their development could find useful pharmacological applications remains to be explored.
A Novel Assay to Measure the Calcium Flux in Human Basophils: Effects of Chemokines and Nerve Growth Factor
Authors: Heinemann Akos , Ofner Martina , Amann Rainer , Peskar Bernhard A.
Published: April 2003

The calcium flux in human basophils was measured by flow cytometry. Peripheral blood mononuclear cells were labeled with anti-CD123 and anti-HLA-DR antibodies, loaded with fluo-3 acetoxymethyl ester (2 µmol/l) in the presence of probenecid (2.5 µmol/l) and Pluronic F-127 (0.02%) for 20 min, and equilibrated with Ca2+ (1.8 mmol/l) and Mg2+ (1 mmol/l) for 5 min. The levels of intracellular free calcium were monitored as changes in fluorescence. Cross-linking of surface IgE on basophils with anti-IgE antibodies caused effective calcium flux in atopic, but not in healthy, donors. Concentration-dependent responses to monocyte chemoattractant protein 1 (MCP-1), eotaxin, macrophage inflammatory protein 1 alpha (MIP-1α), and C5a (0.3–10 nmol/l) were observed in all subjects, with a rank order of potency of C5a = MCP-1 > eotaxin > MIP-1α. In contrast, the rank order of potency in causing basophil shape change (i.e., increase in forward scatter) was eotaxin > C5a > MCP-1 > MIP-1α. Nerve growth factor (NGF; 15 nmol/l) did not induce calcium flux in basophils, and pretreatment of cells with a low concentration of NGF (0.3 nmol/l), which has previously been shown to prime basophils for mediator release, had no effect on the calcium response to subsequent stimulation with C5a. We conclude that calcium mobilization is differentially involved in signaling to chemoattractants in basophils and that it is correlated with the agonist’s efficacy to induce mediator release. The data also suggest that priming of basophil responses by NGF does not rely on enhanced calcium mobilization.
Autosomal Dominant Polycystic Kidney Disease – Clinical and Genetic Aspects
Authors: Bogdanova Nadja , Markoff Arseni , Horst Jürgen
Published: April 2003

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited disorders in humans. It accounts for 8–10% of the cases of end-stage renal disease worldwide, thus representing a serious medical, economical and social problem. ADPKD is in fact a systemic disorder, characterized with the development of cysts in the ductal organs (mainly the kidneys and the liver), also with gastrointestinal and cardiovascular abnormalities. In the last decade there was significant progress in uncovering the genetic foundations and in understanding of the pathogenic mechanisms leading to the renal impairment. This review will retrace the current knowledge about the epidemiology, pathogenesis, genetics, genetic and clinical heterogeneity, diagnostics and treatment of ADPKD.
Ginsenosides Protect Apical Transporters of Cultured Proximal Tubule Cells from Dysfunctions Induced by H2O2
Authors: Han Ho Jae , Yoon Byung Cheol , Park Soo Hyun , Park Ji Yeong , Oh Young Joon , Lee Yun Jung , Park Kwon Moo
Published: April 2003

Oxidative stress has been implicated as a primary cause of renal failure in certain renal diseases. Indeed, renal proximal tubule is a very sensitive site to oxidative stress and retains functionally fully characterized transporters. It has been reported that ginsenosides have a beneficial effect on diverse diseases including oxidative stress. However, the protective effect of ginsenosides on oxidative stress has not been elucidated in renal proximal tubule cells. Thus, we examined the effect of ginsenosides on oxidative stress-induced alteration of apical transporters and its related mechanism in renal proximal tubule cells. In the present study, hydrogen peroxide (H2O2) (>10–5M) inhibited α-methyl-D-glucopyranoside uptake in a dose-dependent manner (p < 0.05). It also inhibited Pi and Na+ uptake. At a concentration of 20 µg/ml, total ginsenosides significantly reduced H2O2-induced inhibition of apical transporters. In contrast, protopanaxadiol (PD) and protopanaxatriol (PT) saponins exhibited a less preventive effect than total ginsenosides (p < 0.05). Furthermore, we examined its action mechanism. H2O2 increased lipid peroxide formation, arachidonic acid (AA) release, and Ca2+ uptake. These effects on H2O2 were significantly prevented by total ginsenosides and PD or PT sanponins. However, total ginsenosides appear to be more protective than PD and PT saponins (p < 0.05). In conclusion, ginsenosides prevented H2O2-induced inhibition of apical transporters via a decrease in oxidative stress, AA release, and Ca2+ uptake in primary cultured renal proximal tubule cells.
‘Safe’ Hyperbilirubinemia Is Associated with Altered Neonatal Behavior
Authors: Mansi G. , De Maio C. , Araimo G. , Rotta I. , Crivaro V. , Sarno M. , Raimondi F. , Paludetto R.
Published: April 2003

Treatment of neonatal jaundice is currently recommended for higher bilirubinemia levels than before. Using the Brazelton Neonatal Behavior Assessment Scale, we found that a series of 28 healthy, untreated, term neonates with moderate bilirubinemia scored significantly less than an equal number of appropriately matched controls with low bilirubinemia for visual and auditory items, both inanimate and animate. Also, a greater lability of state, a lower self-quieting ability and more frequent tremors were found in the jaundiced group. We conclude that hyperbilirubinemia per se, even in the concentration range where phototherapy is not currently recommended, can give rise to alterations in neonatal behavior.
Is Theory of Mind in Schizophrenia More Strongly Associated with Clinical and Social Functioning than with Neurocognitive Deficits?
Authors: Roncone Rita , Falloon Ian R.H. , Mazza Monica , De Risio Alessandro , Pollice Rocco , Necozione Stefano , Morosini PierLuigi , Casacchia Massimo
Published: April 2003

This paper examines the correlations between ‘Theory of Mind’ (ToM) and neurocognitive performance, together with clinical and social functioning, in out-patients with schizophrenic disorders. It was hypothesised that, since the ability to make inferences about the environment and about other peoples’ mental states is a key ingredient of social competence, the assessment of ToM would correlate more strongly with current social functioning than with more traditional neurocognitive measures. ‘Independent raters’ assessed Theory of Mind, neurocognitive and clinical variables as well as community functioning in 44 subjects with schizophrenia. The neuropsychological measures were more closely associated with community functioning than with psychiatric symptoms. These associations remained evident when the effects of intelligence were controlled. Patients with a higher level of competence in making social inferences had better overall community functioning than those who showed less ability in this aspect of social cognition. In a regression model, the capacity to comprehend other people’s mental states (ToM-2) was among the best predictors of global social functioning, together with recent onset of illness, good verbal fluency and low levels of negative and positive symptoms. These results are consistent with other recent findings. ToM measures of social cognition may be a useful addition to neuropsychological assessment when developing programmes for reducing clinical impairments and improving the community functioning of subjects with schizophrenic disorders. Further studies are needed to verify the value of these measures as predictors of the successful application of specific psychosocial rehabilitation strategies.
Changes in Mini-Mental State Exam in Community-Dwelling Older Persons over 6 Years: Relationship to Health and Neuropsychological Measures
Authors: Eslinger Paul J. , Swan Gary E. , Carmelli Dorit
Published: April 2003

Although cognitive screening test scores change with advanced age, the significance of these changes (particularly decline in score) needs to be defined in terms of general health and neuropsychological functioning. Such analysis was undertaken in a subgroup of 287 healthy older men (mean age at baseline = 70.7 years) from the Western Collaborative Group Study, an ongoing cardiovascular and aging research project. Time from baseline to follow-up study averaged 6.0 years (SD = 0.5 years). Mini-Mental State Examination (MMSE) scores indicated that 15% of participants declined by three or more points (a 1+ standard deviation change among all change scores), 5% of participants improved by three or more points, and 80% of the sample remained within two points of their initial score. In health terms, decliners were significantly older, less active at follow-up, rated their health more poorly, and reported more depressive symptoms than non-decliners. Decliners also performed more poorly on several neuropsychological tests administered at follow-up. Results suggest that a decline of three or more points on the MMSE in community-dwelling, older persons without acute illness may signify important changes in health and cognition.
Chronic Fatigue Syndrome: What Role Does the Autonomic Nervous System Play in the Pathophysiology of This Complex Illness?
Authors: Gerrity Timothy R. , Bates Janet , Bell David S. , Chrousos George , Furst Gloria , Hedrick Terry , Hurwitz Barry , Kula Roger W. , Levine Susan M. , Moore Rebecca C. , Schondorf Ronald
Published: April 2003

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800,000 Americans of all ages, races and socioeconomic groups and both genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the autonomic nervous system (ANS). A symposium was organized in December 2000 to explore the possibility of an association between ANS dysfunction and CFS, with special emphasis on the interactions between ANS dysfunction and other abnormalities noted in the immune and endocrine systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting.
Recombinant Human Prolactin Improves Antitumor Effects of Murine Natural Killer Cells in vitro and in vivo
Authors: Sun Rui , Wei Haiming , Zhang Jianhua , Li Ailing , Zhang Weici , Tian Zhi-Gang
Published: April 2003

Objective: To verify the effect of prolactin on natural killer (NK) cells in vivo and its implications for NK cell immunotherapy. Methods: Recombinant human prolactin (rhPRL; 30 µg, i.p.) was administered to BALB/c mice and severe combined immunodeficiency (SCID) mice 1 day before harvesting splenocytes for 51Cr release assay to examine the effects of rhPRL on NK cells of normal mice. rhPRL (10 µg, i.p., every other day for a total of 5 injections) was administered to BALB/c mice after syngeneic bone marrow transplantation (SBMT) to determine its effects on NK cell reconstitution. CT26 tumor cells were injected into BALB/c mice intravenously on day 0, and interleukin (IL)-15-cocultured activated syngeneic NK cells (IL-15-NK) from SCID mice were intravenously injected into tumor-bearing BALB/c mice on day 1. The improvement of antimetastasis effects and survival of tumor-bearing mice by rhPRL were checked. Results: BALB/c and SCID mice receiving one rhPRL injection exhibited a significant increase in cellular cytotoxicity against YAC-1 target tumor cells; the specific lysis was enhanced from 12.5 to 17.3% in BALB/c mice and from 27.8 to 51.2% in SCID mice. BALB/c mice continuously receiving rhPRL injections exhibited significant increases in NK cell (DX5-positive) contents and cellularity in both the bone marrow and spleen in the SBMT model. The bone marrow NK cell contents were improved from 1.53 to 3.13% after rhPRL injection. NK cells from SCID mice were then cultured with recombinant human IL-15 (rhIL-15; 6,000 IU/ml), rhPRL (10 ng/ml) or rhIL-15 plus rhPRL for 25 days. The cytotoxicity and cellularity were enhanced by rhPRL when tested on day 10, when comparing the rhIL-15 plus rhPRL group with the rhIL-15 group or rhPRL group, respectively. In the adoptive cellular immunotherapy study, the IL-15-NK plus IL-15 plus rhPRL group showed significantly lower numbers of lung metastases and longer survival than the IL-15-NK plus IL-15 group; the mean survival interval was prolonged from 31.5 to 53.7 days. Conclusion: These results indicate that rhPRL is possibly an important regulator of NK cells and a potential biologic product for immunotherapy.
Bulimia and Impulsive Behaviour in Middle Adolescence
Authors: Kaltiala-Heino Riittakerttu , Rissanen Aila , Rimpelä Matti , Rantanen Päivi
Published: April 2003

Background: In clinical samples, bulimia seems to be associated with various dyscontrol behaviours suggesting weakness in impulse control. Population studies of adolescents, however, are needed. We evaluated the association between self-reported bulimic behaviour and a number of dyscontrol behaviours, namely bullying, truancy, excessive drinking and sexual disinhibition among adolescents aged 14–16. This is the first study on bulimia and impulsivity in a large non-selected adolescent population sample. Methods: A self-report questionnaire was administered to a representative population sample of 14- to 16-year-old adolescents (pupils of the 8th and the 9th grades of secondary school in four different regions in Finland). 4,453 girls and 4,334 boys aged 14–16 participated. The participation rate was 85.5%. Results: Bulimic behaviour was associated with bullying, truancy, excessive drinking and sexual disinhibition among both sexes. Odds ratios for bulimic-type eating pathology according to each of these behaviours varied between 1.7 and 4.1. The more dyscontrol behaviours occurred simultaneously, the more likely was bulimic-type eating pathology. Conclusions: There is an association between bulimic behaviour and dyscontrol behaviours in the general population of adolescent girls and boys.
The Distribution and Morphological Characteristics of Cholinergic Cells in the Brain of Monotremes as Revealed by ChAT Immunohistochemistry
Authors: Manger Paul R. , Fahringer Heidi M. , Pettigrew John D. , Siegel Jerome M.
Published: April 2003

The present study employs choline acetyltransferase (ChAT) immunohistochemistry to identify the cholinergic neuronal population in the central nervous system of the monotremes. Two of the three extant species of monotreme were studied: the platypus (Ornithorhynchus anatinus) and the short-beaked echidna (Tachyglossus aculeatus). The distribution of cholinergic cells in the brain of these two species was virtually identical. Distinct groups of cholinergic cells were observed in the striatum, basal forebrain, habenula, pontomesencephalon, cranial nerve motor nuclei, and spinal cord. In contrast to other tetrapods studied with this technique, we failed to find evidence for cholinergic cells in the hypothalamus, the parabigeminal nucleus (or nucleus isthmus), or the cerebral cortex. The lack of hypothalamic cholinergic neurons creates a hiatus in the continuous antero-posterior aggregation of cholinergic neurons seen in other tetrapods. This hiatus might be functionally related to the phenomenology of monotreme sleep and to the ontogeny of sleep in mammals, as juvenile placental mammals exhibit a similar combination of sleep elements to that found in adult monotremes.
Nitric Oxide Releases Calcitonin-Gene-Related Peptide from Rat Dura mater Encephali Promoting Increases in Meningeal Blood Flow
Authors: Strecker Thomas , Dux Mária , Messlinger Karl
Published: April 2003

Nitric oxide (NO) and calcitonin-gene-related peptide (CGRP) are implicated in the pathophysiology of vascular headaches. We studied the interaction of these two vasodilatory mediators in an animal model and suggest that NO may increase meningeal blood flow not only by its direct vasodilatory action but also by stimulating CGRP release. First, CGRP release from the rat cranial dura mater was measured in vitro using an enzyme immunoassay. Hemisected skulls with adhering dura mater were filled with synthetic interstitial fluid and stimulated with the NO donor diethylamine-NONOate (10–5–10–3M) or with NO gas (1,000 ppm), which caused concentration-dependent increases in CGRP release up to 166.8%. Second, meningeal blood flow was recorded in vivo in the exposed dura mater using laser Doppler flowmetry. Topical application of the NO donors NONOate, S-nitroso-N-acetylpenicillamine and N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino)-ethenamine (10–5–10–3M) caused concentration-dependent increases in blood flow. These increases were significantly reduced by local preliminary application of the CGRP receptor antagonist CGRP8–37 (10–4M). We conclude that NO stimulates the release of CGRP from dural afferents. The blood-flow-increasing effect of NO seems to be partly mediated by CGRP. The interaction of NO and CGRP may be relevant for the development of vascular headaches.
An ELISA Assay for the Detection of Factor VIII Antibodies – Comparison with the Conventional Bethesda Assay in a Large Cohort of Haemophilia Samples
Authors: Shetty Shrimati , Ghosh Kanjaksha , Mohanty Dipika
Published: April 2003

An enzyme-linked immunosorbent assay (ELISA) has been developed to measure factor VIII antibodies in haemophilia patients. The assay utilizes binding of the antibodies in the plasma to solid phase antigen, i.e. recombinant factor VIII which was subsequently detected by a human polyclonal IgG labelled with the alkaline phosphatase-p-nitrophenyl phosphate substrate system. Comparisons were made with the Bethesda assay for the quantitation of factor VIIII inhibitors. Dose response curves for the reference standards were consistently linear and reproducible. The assay was specific for factor VIII antibodies, showing a negative reaction for antibodies to other coagulation factors, antinuclear factors and antiphospholipid antibodies. Using this method, 312 samples from haemophilia A patients and 31 samples from healthy controls were screened for the presence of inhibitors and compared with the conventional Bethesda assay. Twenty-four cases were found to be positive for inhibitors in both the ELISA and Bethesda assay. Five additional cases were also found to be positive in the ELISA assay, which, however, were negative in Bethesda assay. One patient who was initially positive for factor VIII inhibitors both by the Bethesda assay and ELISA eventually became negative for the Bethesda assay (<0.5 BU/ml) but was still positive for the ELISA assay. The ELISA thus described had a specificity of 97.8% and a sensitivity of 100% when tested against a large cohort of haemophilia A samples.
In vitro Autoreactivity against Skin and Synovial Cells in Patients with Juvenile Idiopathic and Rheumatoid Arthritis
Authors: Stechova Katerina , Vavrincova Pavla , Chudoba Daniel , Frantlova Miroslava , Reitzova Helena , Sosna Antonin , Zimak Jaroslav , Lednicky Ladislav , Dickinson Anne Mary , Hromadnikova Ilona
Published: April 2003

In the present study we compared specific lysis of various autologous target cells in patients with juvenile idiopathic arthritis JIA; n = 8) or rheumatoid arthritis RA; n = 17) with those of healthy controls (n = 15). 51Cr-release cytotoxic assay with autologous peripheral blood mononuclear cells as effector cells was used. When compared with controls, effector cells of patients with JIA or RA were found to lyse significantly autologous synovial cells (p < 0.0005) and epidermal keratinocytes (p < 0.0005), however, no difference was found for autologous dermal fibroblasts.
Trypanosoma cruzi Infection Impairs the Endocytosis of Zymosan A by Cardiomyocytes
Authors: Soeiro M.N.C. , Mota R.A. , Batista D.G.J. , Pereira M.C.S. , Meirelles M.N.L.
Published: April 2003

Objective: We have previously reported that mannose receptors participate and are regulated during Trypanosoma cruzi cardiomyocyte (CM) infection. Our present aim is to characterize the endocytosis of mannosylated ligands like zymosan A (Zy) in uninfected and T. cruzi-infected CM. Methods: CM infected or not by T. cruzi wereincubated with Zy for different periods of time and their internalization was analyzed at light microscopy level. Fluorescent approaches were performed by treating Zy with concanavalin-A-TRITC and washing it exhaustively prior to incubation with CM. The cultures were further stained with phalloidin-FITC and DAPI for actin and DNA visualization, respectively. Results: CM internalized Zy particles in a time-dependent fashion. The ligand specificity was confirmed by the addition of mannan, which efficiently blocked the Zy endocytosis. Designed fluorescent approaches extended and confirmed the Zy internalization by striated cells. Infected cultures displayed impairment in Zy endocytosis, which seems to be directly related to host infection rates. Conclusions: Altogether, our results show the ability of CM to ingest large particles such as the mannosylated ligand Zy. During their infection with T. cruzi, there is a loss in Zy internalization possibly due to the negative modulation of mannose receptors.
Elution of IgA from Kidney Tissues Exhibiting Glomerular IgA Deposition and Analysis of Antibody Specificity
Authors: Ogawa Yayoi , Ishizu Akihiro , Ishikura Hiroshi , Yoshiki Takashi
Published: April 2003

Glomerular IgA deposits were eluted from renal biopsy specimens exhibiting IgA nephropathy (IgAN) by using a combination of citrate buffer and collagenase. Collagenase predigestion of the kidney tissues resulted in increased amounts of IgA eluted by citrate buffer, and the elusion procedure did not attenuate the antigen-binding ability of IgA antibody. When reactivity of the eluted IgA with bacteria components was examined by Western blotting, the most notable reaction was observed for Haemophilus influenzae lysates in the form of a 34 kD-band. The reactivity of IgA eluted from the kidney tissues against the H. influenzae 34 kD antigen was evident in 3 of 5 IgAN cases. However, similar reactivity was also evident in 2 of 6 non-IgAN hepatic diseases exhibiting a glomerular IgA deposition. These findings suggest that antibody specificity of IgA against H. influenzae itself may not be directly associated with glomerular injury, although anti-H. influenzae 34 kD IgA was deposited in the kidney, at least in part, by IgAN. Further investigations into the properties of IgA deposited in the glomerulus are needed. Our improved method for IgA elution from kidney tissues would be useful for analysing the pathogenesis of IgAN.
Effects of Hemoglobin on Pulmonary Arterial Pressure and Pulmonary Vascular Resistance in Patients with Chronic Emphysema
Authors: Nakamura Akira , Kasamatsu Norio , Hashizume Ikko , Shirai Takushi , Hanzawa Suguru , Momiki Shigeru , Sasaki Kazuyoshi , Kinoshita Masao , Okada Osamu , Tatsumi Koichiro , Kuriyama Takayuki
Published: April 2003

Background: The increase in viscosity caused by secondary polycythemia is thought to be one of the major causes of pulmonary hypertension secondary to chronic emphysema. However, very few clinical studies considered the relation between pulmonary hypertension and polycythemia in the case of chronic obstructive pulmonary disease. Objective: The purpose of this study is to elucidate the relative contribution of an increase in hemoglobin level (Hb) to mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR). Methods: We retrospectively investigated 41 patients with chronic emphysema who had undergone a right heart catheterization. Multiple-regression analysis and F test were performed to investigate both direct effects of Hb and PaO2 as independent variables on mPAP and PVR as dependent variables. Results: Significant correlations were found between PaO2 and mPAP (or PVR), or Hb and mPAP (or PVR), indicating that both Hb and PaO2 are contributory to mPAP and PVR. The F test demonstrated that Hb and PaO2 could directly affect the level of either mPAP or PVR. Conclusions: It was concluded that Hb had a direct effect on mPAP and PVR, independently of hypoxia in patients with chronic emphysema.
Review of Cases with Cystic Hydatid Lung Disease in a Tertiary Referral Hospital Located in an Endemic Region: A 10 Years’ Experience
Authors: Tor Meltem , Atasalihi Ali , Altuntas Nejat , Sulu Ebru , Senol Tuncer , Kir Altan , Baran Reha
Published: April 2003

Background: Echinococcus disease is endemic in sheep-and cattle-raising areas world wide. Its prevalence is also high in the Mediterranean region including Turkey. Objective: To determine the presentation, approach to surgical treatment and outcome of hydatid disease in an endemic region. Methods: From January 1989 to December 1998 288 patients, aged between 1 and 71 years with a mean age of 31 years (134 female, 154 male), were operated on for pulmonary hydatidosis. Clinical charts of the patients were reviewed retrospectively in a tertiary referral hospital. Results: Of 288 patients, 30 patients were asymptomatic, the rest (89%) were symptomatic, cough and chest pain being the most common symptoms. Fifty-three patients (18%) had associated liver hydatid cysts. Bilateral lung hydatid cysts were present in 18 patients (6%). Recurrent hydatid cysts were observed in 33 patients (11%). Seventy-seven patients (27%) presented with complicated hydatid cysts. Postoperative morbidity was observed in 3 patients [bronchopleural fistula (2), infection of the cyst space (1)] and postoperative mortality in 1 patient who presented with hydatid lung disease associated with liver and brain cysts. In the remaining 98.6%, no complications were noted. Conclusions: In conclusion, hydatidosis is still an important public health problem in Turkey and in an endemic country such as Turkey hydatid lung disease should be considered initially in a patient presenting with a corresponding chest roentgenogram and a compatible epidemiologic history. Surgery is indicated in all symptomatic and/or enlarging or infected cysts. When necessary lobectomy or wedge resection can be the procedure of choice. Single-stage combined resection is preferred in hydatid lung disease with associated liver hydatid cysts. Total postoperative complication and mortality rate is low and we recommend a close follow-up of the operated cases to diagnose postoperative recurrence early in its course.
Inhibitory Effect of N-Acetylcysteine on Adherence of Streptococcus pneumoniae and Haemophilus influenzae to Human Oropharyngeal Epithelial Cells in vitro
Authors: Riise Gerdt C. , Qvarfordt Ingemar , Larsson Sven , Eliasson Viktoria , Andersson Bengt A.
Published: April 2003

Background: Bacterial adherence to mucosal and epithelial cell structures is of importance for the persistence of bacteria in the airways. Cigarette smoking and chronic bronchitis are associated with increased bacterial adherence. N-Acetylcysteine (NAC) medication reduces the number of infectious exacerbations in patients with chronic bronchitis, and NAC medication has been associated with low intrabronchial bacterial numbers. Objective: We investigated whether NAC influences bacterial adherence as a possible mechanism behind its clinical effects. Methods: Highly adhering test strains of Streptococcus pneumoniae and Haemophilus influenzae were used to investigate the influence of four pharmacological compounds on adherence to oropharyngeal epithelial cells in vitro. Adhesion assays were performed both during short-term exposure to, as well as after long-time incubation with, NAC, lidocaine, hydrocortisone and terbutaline at concentrations not inhibiting bacterial growth. Results: Only NAC showed a significant inhibitory effect on adhesion of H. influenzae during short-term incubation. After long-term incubation, both NAC and hydrocortisone inhibited bacterial adhesion for both strains in a dose-dependent manner. When NAC’s effect on three different strains of S. pneumoniae and four strains of H. influenzae was studied, inhibition of bacterial adhesion was found for three strains of each species. Conclusions: NAC lowers bacterial adhesion in vitro to oropharyngeal epithelial cells in doses equivalent to that is being used clinically. This effect might be a contributory mechanism behind the reduction of infectious exacerbations in chronic bronchitis patients.
Update on Treatment of Variceal Hemorrhage
Authors: Wu Justin C.Y. , Sung Joseph J.Y.
Published: April 2003

Variceal hemorrhage accounts for one third of all deaths related to cirrhosis. To date, many modalities of treating variceal bleeding have been devised, including pharmacological therapy. Treatment of variceal hemorrhage includes resuscitation, initial hemostasis, and prevention of complications and recurrent bleeding. Intravenous vasoactive agents such as terlipressin, somatostatin, octreotide, or vapreotide should be administered in patients with suspected variceal bleeding. Endoscopic treatment remains the mainstay of treatment. Endoscopic variceal ligation is safer and more efficacious than sclerotherapy as initial treatment of bleeding esophageal varices, whereas cyanoacrylate injection is the endoscopic treatment of choice for gastric varices. An adjuvant vasoactive agent is useful for the prevention of early rebleeding. Prophylactic antibiotics are increasingly used for prevention of infection, notably spontaneous bacterial peritonitis. Follow-up endoscopic treatment is necessary in order to obliterate residual varices. The combination of a beta blocker and nitrate is an essential component of secondary prophylaxis for recurrent variceal bleeding. Transjugular intrahepatic portosystemic shunt or surgery offers the best salvage therapy in patients with failed hemostasis or breakthrough recurrent bleeding despite medical and endoscopic therapy. Endoscopic ultrasonography is useful in the prediction of recurrence of varices and facilitates visualization and guidance of further treatment of gastric varices. Despite advances in the treatment of variceal bleeding, liver function remains the determining factor of patient survival. Liver transplantation is the only definitive treatment that can alter the course of the disease.
Treatment of Benign Biliary Strictures in Chronic Pancreatitis by Self-Expandable Metal Stents
Authors: Kahl Stefan , Zimmermann Sandra , Glasbrenner Bernhard , Pross Matthias , Schulz Hans-Ulrich , McNamara Deirdre , Malfertheiner Peter
Published: April 2003

Aim: To determine the efficacy the value of self-expandable metal stents in patients with benign biliary strictures caused by chronic pancreatitis. Method: 61 patients with symptomatic common bile duct strictures caused by alcoholic chronic pancreatitis were treated by interventional endoscopy. Results: Initial endoscopic drainage was successful in all cases, with complete resolution of obstructive jaundice. Of 45 patients who needed definitive therapy after a 12-months interval of interventional endoscopy, 12 patients were treated with repeated plastic stent insertion (19.7%) or by surgery (n = 30; 49.2%). In 3 patients a self-expandable metal stent was inserted into the common bile duct (4.9%). In patients treated with metal stents, no symptoms of biliary obstruction occurred during a mean follow-up period of 37 (range 18–53) months. The long-term success rate of treatment with metal stents was 100%. Conclusions: Endoscopic drainage of biliary obstruction by self-expandable metal stents provides excellent long-term results. To identify patients who benefit most from self-expandable metal stent insertion, further, prospective randomized studies are necessary.