bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between Surfactant and Ventilatory Support in Newborns with Primary Surfactant Deficiency
Authors: Plavka Richard , Keszler Martin
Published: July 2003

The interaction between exogenous surfactant and various modes of ventilatory support in terms of timing, quality and quantity can influence both short- and long-term outcomes of immature infants. Alterations to the pulmonary surfactant system can occur with all forms of mechanical ventilation. Experimental data suggest possible interaction between ventilatory support and exogenous surfactant even during the first breaths in the delivery room. The adverse effect on surfactant function at this time can increase the need for and duration of ventilatory support. The logical approach to ventilatory support is to be minimally aggressive with optimal recruitment of the lungs to avoid ventilator-induced lung injury. Nasal continuous positive airway pressure (CPAP) in combination with early prophylactic surfactant administration may be an effective and less damaging method capable of reducing the need of artificial ventilation, but its benefit has not been proven in extremely preterm infants less than 28 weeks’ gestation. Because of unproven efficacy of nasal CPAP in extremely premature infants, the population most at risk for adverse pulmonary and neurologic outcome, this paper focuses on the comparison of conventional and high-frequency oscillatory ventilation (HFOV) with respect to alteration of surfactant function, and short- and long-term outcomes, in both human and experimental trials. Though the two most recent large clinical trials provide reassurance with respect to the safety of first-intention high-frequency ventilation, the reduction in the risk of chronic lung disease appears to be only modest or absent. Recent laboratory investigations suggest that the key element of HFOV, namely optimization of volume, can, under some circumstances, be replicated with low tidal volume conventional ventilation and high positive end-expiratory pressure. Recent introduction of patient-triggered volume-targeted conventional ventilation into clinical practice offers the promise of a practical means of providing gentle conventional ventilation capable of minimizing ventilator-induced lung injury. Ultimately, well-designed comparative clinical trials with long-term outcomes are essential to accurately quantify risks and benefits of any new approach to mechanical ventilation. Without such data, these experimental results should not be extrapolated into clinical practice, because of the multifactorial pathophysiology of the development of chronic pulmonary disease in extremely premature infants and the risk of unanticipated adverse effects.
Current Dilemmas in Postnatal Steroid Therapy for Chronic Lung Disease in Preterm Infants
Authors: Shinwell Eric S.
Published: July 2003

Postnatal steroid therapy has been widely used for the prevention and treatment of chronic lung disease in preterm infants. Recently, evidence has accumulated to suggest that the risks of therapy may outweigh the possible benefits. In 2002, the American Academy of Pediatrics and the Canadian Paediatric Society issued guidelines for steroid use. While clarifying a confusing situation, these guidelines have given rise to much controversy. This review will summarize current information on the clinical trials of steroids and also consider the issues surrounding the guidelines.
Efficacy of 8-Bromoguanosine against Murine Cutaneous Leishmaniasis Induced with Leishmania amazonensis
Authors: Barão Sandra Cristina , Giorgio Selma
Published: July 2003

Background and Methods: In this study, we investigated the effect of 8-bromoguanosine (8Brguo), an immunostimulatory compound, in a murine model of experimental cutaneous leishmaniasis. Results: The results indicated that treatment by intraperitoneal administration of 8Brguo (150 mg/kg once daily for 1 week and thereafter once weekly for 1 month) diluted in Tween-80 produces an effect similar to that of treatment with the classical antimonial drug, Glucantime, in Leishmania amazonensis-infected CBA/J mice. While complete cure did not occur, animals treated with the nucleoside had small lesions in the infected footpad and delayed surface ulceration. Studies involving examination of serum glutamic pyruvic transaminase activity, concentration of urea, blood pathology and histology of the spleen, kidney and liver showed no apparent toxicity of the nucleoside in treated mice. Conclusion: The protective in vivo effect during murine leishmaniasis as well as the lack of apparent toxicity of 8Brguo as attested by blood/serum pathology and histology from treated mice encourage further studies of C8-substituted guanine ribonucleosides, such as 8Brguo, as new leishmanial drugs and as modifiers of the immunological response to combat infections with intracellular pathogens.
Effect of Linezolid on the Phagocytic Functions of Human Polymorphonuclear Leukocytes
Authors: Ballesta Sofía , Pascual Álvaro , García Isabel , Perea Evelio J.
Published: July 2003

The effect of linezolid on the phagocytic and bactericidal functions of human polymorphonuclear neutrophils (PMN) against gram-positive cocci was evaluated. Preincubation (30 min; 37°C) of PMN with different concentrations of linezolid (2, 10 and 20 mg/l) did not significantly affect the phagocytosis of either Staphylococcus aureus (methicillin susceptible and resistant) or Enterococcus faecalis (vancomycin susceptible and resistant). Overnight exposure of vancomycin-resistant E. faecalis to 1/4 minimum inhibitory concentrations (MIC) of linezolid slightly increased phagocytosis by PMN. Preincubation of the other three strains with 1/4 MIC of linezolid did not affect phagocytosis by these cells. Preincubation of PMN (30 min; 37°C) using different extracellular concentrations of linezolid (2, 10 and 20 mg/l) did not affect their production of either superoxide or hydrogen peroxide radicals. In conclusion, linezolid did not affect the phagocytic and bactericidal functions of human PMN.
The Penetration of Moxifloxacin into the Pancreas of Male Rats in Experimental Acute Necrotizing Pancreatitis
Authors: Wacke Rainer , Park Sora , Mundkowski Ralf G. , Block Norma , Kuhn-Thiel Alexandra , Drewelow Bernd
Published: July 2003

Infectious complications of acute necrotizing pancreatitis (ANP) determine the extent of multiorgan failure and account for 80% of deaths. Prophylactic use of antibiotics can reduce the incidence of these complications. However, the actual indication as well as choice of drug remains a controversial matter. We examined the penetration of moxifloxacin, a new broad-spectrum fluoroquinolone, in healthy and inflamed pancreatic tissue in rats after inducing ANP. The concentration of moxifloxacin in pancreatic tissue and serum was determined 10, 30, 60 and 240 min after the administration of moxifloxacin (5 mg/kg, i.v.). Mean serum concentrations 10 min after administration in rats with ANP were 1,886 ng/ml versus 1,805 ng/ml in healthy controls, and these values decreased to 350 versus 222 ng/ml, respectively, after 240 min. Corresponding concentrations in pancreatic tissue were in the mean 2–3 times higher.
Target Affinities of Faropenem to and Its Impact on the Morphology of Gram-Positive and Gram-Negative Bacteria
Authors: Dalhoff A. , Nasu T. , Okamoto K.
Published: July 2003

Faropenem is a new oral β-lactam antibiotic unique from carbapenems and other available β-lactams. Determinants of the in vitro activity of β-lactam antibiotics include affinity to penicillin-binding proteins (PBPs) and β-lactamase stability. In this study, the binding affinity of faropenem to various PBPs and its impact on the morphology of Staphylococcus aureus and Escherichia coli were evaluated. In general, faropenem demonstrated high binding affinity to high-molecular-weight PBPs but low affinity to low-molecular-weight PBPs. In S. aureus and Streptococcus pneumoniae, faropenem exhibited high binding affinity to PBP1, followed by PBP3 and PBP2. In E. coli, faropenem showed the highest affinity for PBP2, followed by PBP1A, PBP1B, PBP3 and PBP4. In Proteus vulgaris, binding was highest to PBP4, followed by PBP1A, PBP2 and PBP3. In Serratia marcescens, faropenem bound preferentially to PBP2 and PBP4. Exposure of S. aureus to faropenem at minimum inhibitory concentrations (MICs) of 1/8 or 1/4 resulted in irregular septum formation. At 1× MIC or higher, a larger number of lysed cells were observed. Exposure of E. coli to 1/8× MIC or 1/4× MIC also induced changes in cellular shape; the normal rod-shaped form changed to a spherical form in a time-dependent manner. After exposure of E. coli to 1× MIC for 2 h, bulging-shaped E. coli cells were observed and after 4 h of exposure cell lysis was demonstrated. In the presence of 4× MIC, spheroplast-like forms and cell lysis were observed. The morphological changes triggered by faropenem are in agreement with the PBP binding affinities reported. Thus, the high binding affinities of faropenem to PBPs from gram-negative and gram-positive bacteria are mirrored by its pronounced and concentration-dependent bactericidal effect.
Comparative in vitro Activity of Three Fluoroquinolones against Clinical Isolates by E Test
Authors: Madhusudhan Kunapuli T. , Counts Carolyn , Lody Cecilia , Carter Ophelia , Dodson Sarah , Ojha Neelam
Published: July 2003

The in vitro susceptibility of levofloxacin, ciprofloxacin and moxifloxacin against several gram-positive and gram-negative clinical isolates was tested by E test. We found that the MIC50 and MIC90 values against all members of the Enterobacteriaceae family except Serratia were <0.5 mg/l for ciprofloxacin and levofloxacin (MIC range 0.006–32 mg/l) based on the in vitro susceptibility data. The susceptibility rates for ciprofloxacin and levofloxacin were more than 85% for Escherichia coli, Citrobacter, Enterobacter cloacae, Enterobacter aerogenes and Klebsiella pneumoniae, although Serratia and Acinetobacter exhibited more or less similar susceptibility rates (about 80%). Pseudomonas aeruginosa demonstrated significant resistance to fluoroquinolones (MIC90 >32 mg/l) and decreased bactericidal rates (<65%) to levofloxacin and ciprofloxacin. Respiratory pathogens such as Streptococcus pneumoniae and Haemophilus influenzae were highly susceptible (100%) to levofloxacin and moxifloxacin. The ineffectiveness of fluoroquinolones for treating coagulase-positive Staphylococcus aureus was demonstrated by poor in vitro susceptibility rates with levofloxacin (52%) and moxifloxacin (57%). Coagulase-negative staphylococci demonstrated significantly decreased bactericidal rates to levofloxacin (21%), while the in vitro susceptibility to moxifloxacin was higher (66%) than that to levofloxacin. We propose that the beneficial effect of inclusion of any of these three fluoroquinolones in treating Enterococcus infections is marginal, as demonstrated by significantly reduced susceptibility rates (<32%). These data demonstrate the utility of fluoroquinoles to treat several gram-negative bacterial infections (with the exception of Acinetobacter and P. aeruginosa), as well as S. pneumoniae and H. influenzae.
Antimicrobials as Potential Adjunctive Agents in the Treatment of Biofilm Infection with Staphylococcus epidermidis
Authors: Peck Kyong Ran , Kim Shin Woo , Jung Sook-In , Kim Yeon-Sook , Oh Won Sup , Lee Ji Young , Jin Joung Hwa , Kim Sungmin , Song Jae-Hoon , Kobayashi Hiroyuki
Published: July 2003

Background: This study was performed to evaluate the interaction of erythromycin or rifampin with vancomycin against Staphylococcus epidermidis biofilms. Methods: Biofilm-forming S. epidermidis strains (ATCC 35983, 35984) and polyurethane (PU) sheets were incubated for the formation of bacterial biofilms. Biofilms on PU sheets were treated with various antibiotic regimens. The number of viable bacteria on the sheets was counted. Results: While erythromycin or vancomycin alone did not significantly reduce the biofilm bacterial concentration, the combination of vancomycin and erythromycin resulted in a clear reduction in bacterial concentration compared with the single agents. Rifampin was the most active single agent against biofilm-forming S. epidermidis, while the combination of rifampin and vancomycin showed further reduction in bacterial concentration. Conclusions: These data suggest that the combination of erythromycin or rifampin and vancomycin is more effective than vancomycin alone in the treatment of biofilm infections caused by biofilm-forming S. epidermidis.
Oxaliplatin with Weekly Bolus 5-Fluorouracil and Leucovorin in Pretreated Advanced Colorectal Cancer Patients: A Phase II Study
Authors: Yang Tsai-Shen , Chen Jinn-Shium , Tang Reiping , Chiang Jy-Ming , Hsieh Pau-Shiu , Yeh Chien-Yu , Changchien Chung-Rong
Published: July 2003

Background: The purpose of this study was to determine the efficacy and toxicity of oxaliplatin in combination with weekly bolus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with 5-FU-pretreated advanced colorectal cancer. Methods: A total of 39 patients with documented 5-FU-resistant advanced colorectal cancer were enrolled. All 39 patients had previously received weekly high-dose 5-FU/LV (2,600 mg/m2 5-FU plus 100 mg/m2 LV as 24-hour infusion) as first-line chemotherapy for metastatic disease. Oxaliplatin (85 mg/m2) was delivered as an intravenous infusion over 2 h on days 1 and 15, while 5-FU (500 mg/m2) and LV (20 mg/m2) were administered as an intravenous bolus on days 1, 8 and 15. One treatment course consisted of 3 consecutive weeks of therapy followed by a 1-week rest. Results: In an intent-to-treat analysis, the objective response rate for the 39 patients was 20.5% (95% confidence interval, 7.2–33.8%). The disease was stable in 19 patients (48.7%), and progressive in 11 (28.2%). The median survival for all 39 patients was 8.9 months. The median time to progression was 5.0 months. Grade 3/4 neutropenia occurred in only 1 patient (2.6%), and grade 2 and 3/4 peripheral neuropathy occurred in 10 (25.6%) and 5 (12.8%) patients, respectively. Conclusion: Oxaliplatin in combination with weekly bolus 5-FU/LV is also active in patients with advanced colorectal cancer where first-line treatment has failed.
Combination Chemotherapy with Irinotecan and Ifosfamide as Second-Line Treatment of Refractory or Sensitive Relapsed Small Cell Lung Cancer: A Phase II Study
Authors: Ichiki Masao , Gohara Rumi , Rikimaru Toru , Kitajima Takao , Fujiki Rei , Shimada Akiko , Aizawa Hisamichi
Published: July 2003

This phase II study was conducted to investigate the efficacy and safety of irinotecan (CPT-11) and ifosfamide as second-line chemotherapy for relapsed small cell lung cancer (SCLC). Eligibility criteria included histologically or cytologically confirmed SCLC, prior chemotherapy including platinum + etoposide, and measurable or evaluable disease. CPT-11 (80 mg/m2) was administered intravenously on days 1, 8 and 15, while ifosfamide (1.5 g/m2) was given on days 1 through 3 every 4 weeks. Thirty-four patients (29 men) with a median age of 69 years (range 42–77) and a median Eastern Cooperative Oncology Group (ECOG) performance status of 1 (range 0–2) were enrolled. The response rate was 52.9% (95% confidence interval: 29.8–64.9%) with 2 complete responses and 16 partial responses. Our analyses of prognostic factors showed risk factors assessed before receiving second-line chemotherapy, which were the number of metastatic sites, performance status and the type of relapse. WHO grade 3–4 neutropenia was recorded in 52.9% of the patients, grade 3 diarrhea in 5.9%. The combination of CPT-11 and ifosfamide demonstrated clinical efficacy in relapsed SCLC with a favorable toxicity profile, particularly for performance status 0–1 and sensitive cases with only one metastatic site.
Ampicillin, Gentamicin and Teicoplanin as Antimicrobial Therapy for Recurrent Streptococcus agalactiae and Enterococcus faecalis Endocarditis in an Intravenous Drug Abuser with HIV Infection
Authors: Calza Leonardo , Manfredi Roberto , Marinacci Ginevra , Fortunato Lorenza , Chiodo Francesco
Published: July 2003

Infective endocarditis associated with human immunodeficiency virus (HIV) infection occurs almost exclusively in intravenous (i.v.) drug users and usually involves the tricuspid valve, with an increased mortality rate among patients with a severe degree of immunosuppression. The first reported case of recurrent tricuspid endocarditis sustained by Streptococcus agalactiae and Enterococcus faecalis in an i.v. drug addict during HIV infection is presented. Antimicrobial therapy with i.v. ampicillin, gentamicin and teicoplanin led to complete clinical and echocardiographical recovery.
Lung, Pleural and Colon Actinomycosis in an Immunocompromised Patient: A Rare Form of Presentation
Authors: Charalabopoulos K. , Charalabopoulos A.K. , Papalimneou V. , Ioachim E. , Constantopoulos S.H.
Published: July 2003

Actinomycosis is caused by gram-positive filamentous organisms of the genus Actinomyces, which may spread through trauma. Most commonly, it is a cervicofacial disease due to dental infection or a thoracic disease secondary to aspiration of foreign bodies. Primary abdominal infection usually follows some form of mucosal disruption. Any organ of the human body may be involved so that a wide range of symptoms may be present. We report a rare form of actinomycosis involving the lung, pleura and colon concomitantly in an immunocompromised patient. A fine needle aspiration from a lung lesion detected the characteristic sulfur granules, and a pleural effusion culture confirmed the diagnosis. Clinical manifestations and treatment are discussed. Actinomycetes are rarely opportunistic agents in immunocompromised patients; thus the disease deserves special attention in those patients.
Downregulation of Superoxide Dismutase Activity and Gene Expression in Cultured Rat Brain Astrocytes after Incubation with Vitamin C
Authors: Kao Pai-Feng , Lee Wen-Sen , Liu Ju-Chi , Chan Paul , Tsai Jen-Chen , Hsu Yung-Ho , Chang Wen-Yin , Cheng Tzu-Hurng , Liao Shue-Sen
Published: July 2003

Reactive oxygen species have been linked with neuropathological changes in the central nervous system. Epidemiological studies supported the beneficial effect of supplementation of antioxidants. Superoxide dismutase (SOD) is an endogenous enzyme which can scavenge reactive oxygen species. This study investigated the effect of supplementation with ascorbic acid (vitamin C) on the changes of SOD in cultured neurological cells. Rat brain astrocytes (RBA-1 cells) were incubated with vitamin C and divided into four groups: a control group (without vitamin C) and three treatment groups with vitamin C at 40, 80, and 160 µmol/l. After short-term (2 days) and long-term (7 days) incubation, SOD activity, SOD mRNA level by Northern blotting, and SOD protein amounts by Western blotting were measured. After 2 days of incubation, vitamin C resulted in a decrease in the activity of SOD in a concentration-dependent manner (Mn-SOD from 14.8 ± 1.2 to 13.2 ± 0.5 U/mg protein and Cu/Zn-SOD from 64.8 ± 1.2 to 51.7 ± 0.9 U/mg protein; p < 0.05), and vitamin C also attenuated the Cu/Zn-SOD mRNA level from 100 to 86.3 ± 6.7%; p < 0.01), whereas the protein amounts of these two SODs remained unchanged. After 7 days of incubation with vitamin C, the SOD activity of RBA-1 cells decreased significantly (Mn-SOD from 14.9 ± 0.3 to 11.8 ± 0.3 U/mg protein and Cu/Zn SOD from 61.8 ± 1.8 to 54.6 ± 0.9 U/mg protein; p < 0.01), and the mRNA level was also attenuated (Mn-SOD from 100 to 86.8 ± 8.7% and Cu/Zn-SOD from 100 to 84.7 ± 4.8%; p < 0.01). These results suggest that 2 and 7 days of incubation with relatively high concentrations of vitamin C may downregulate activity and gene expression of SOD in cultured RBA-1 cells.
Effect of Endothelin on Bladder Contraction: Potential Role in Bladder Hyperactivity
Authors: Westfall Timothy D. , McCafferty Gerald P. , Pullen Mark , Ventre Jessica , Eybye Marianne , Jugus Malcolm J. , Brooks Stuart A. , Hieble J. Paul , Brooks David P.
Published: July 2003

In the present study, we demonstrate that the intravenous infusion of endothelin-1 (3 and 10 ng/kg/min) causes a decrease in the mean micturition volume of rats in addition to an increase in mean arterial pressure. These effects are blocked by both the ETA/ETB-non-selective and the ETA-selective endothelin antagonists SB 217242 and SB 247083 respectively (both 30 mg/kg). However, it was also observed that the ETB-selective agonist sarafotoxin 6c (3 and 10 ng/kg/min) had similar effects on both mean arterial pressure and micturition volume. Initial experiments indicated that spontaneously hypertensive rats have a much lower mean micturition volume than normal rats. Binding studies comparing the total number and ratio of ETA/ETB receptors in spontaneously hypertensive, Wister-Kyoto and Sprague-Dawley rats revealed no significant differences in receptor expression. However, the magnitude of the response to endothelin-1 was greater in spontaneously hypertensive versus normal rats.
Roles of Reactive Oxygen Species, NF-κB, and Peroxiredoxins in Glycochenodeoxycholic Acid-Induced Rat Hepatocytes Death
Authors: Chu Sang Hui , Lee-Kang Jihee , Lee Kweon-haeng , Lee Kyungeun
Published: July 2003

The aim of this study was to determine the roles of reactive oxygen species (ROS), NF-ĸB and antioxidants in glycochenodeoxycholic acid (GCDC, 0–400 µmol/l, 0.5– 3 h)-induced hepatocytes death. The differential uptake of ethidium bromide and acridine orange revealed that apoptotic death occurred dose-dependently in GCDC-treated hepatocytes whereas necrotic death was prominent especially at higher GCDC concentrations (≧200 µmol/l). ROS generation measured fluorometrically either by a confocal laser microscope or by a microplate fluorescence reader was increased dose-dependently. The dose-dependent NF-ĸB activation with the significant IĸB-α decrease preceded both hepatocyte cell death and the alteration of antioxidant enzymes. The Cu/Zn-SOD level among several antioxidants, we checked, remained unchanged. In contrast, the catalase level and its enzymatic activity were markedly decreased only at 400 µmol/l. The Prx I and Prx II, newly defined antioxidant enzymes reducing H2O2 levels were decreased at the 200 and 400 µmol/l. These observations point to ROS generation in the GCDC-treated hepatocyte as the proximate event that triggers NF-ĸB activation, IĸB-α proteolysis, Prx depletion, and finally cell death. And oxidative stress may be more related to necrotic cell death in GCDC-treated hepatocytes.
Effects of Endogenous Histamine on Seizure Development of Pentylenetetrazole-Induced Kindling in Rats
Authors: Zhang Li-San , Chen Zhong , Huang Yu-Wen , Hu Wei-Wei , Wei Er-Qing , Yanai Kazuhiko
Published: July 2003

This study was performed to investigate whether or not endogenous histamine can protect seizure development of pentylenetetrazole (PTZ)-induced kindling in rats. An intracerebroventricular (i.c.v.) injection with clobenpropit (5 and 10 µg), a representative H3-antagonist, significantly prolonged the onset of kindling and inhibited the seizure stages in a dose-dependent manner. Its action was significantly reversed by both immepip (2 µg, i.c.v.), an H3-agonist, and α-fluoromethylhistidine (α-FMH, 10 µg, i.c.v.), a selective histidine decarboxylase inhibitor. α-FMH (20 µg, i.c.v.) and pyrilamine (1 and 5 mg/kg i.p.), a classical H1-antagonist, markedly augmented the severity of seizure development of PTZ-induced kindling. Therefore, these results indicate that brain endogenous histamine plays a certain protective role on seizure development of PTZ-induced kindling in rats, and that its protective roles are mediated by H1-receptors.
P2Y1 Receptor Activation Enhances the Rate of Rat Pinealocyte-Induced Extracellular Acidification via a Calcium-Dependent Mechanism
Authors: Ferreira Zulma Silva , Garcia Célia Regina S. , Spray David C. , Markus Regina P.
Published: July 2003

Pineal gland G-protein coupled P2Y1 receptors potentiate noradrenaline-induced N′-acetylserotonin production, a long term response which occurs after 5 h incubation. In the current study we show that a short-term effect of stimulation of P2Y1 receptors is the increase in extracellular acidification rate (ECAR), which is mediated by an increase in intracellular calcium concentration ([Ca2+]i). The pD2 values for ATP (3.06 ± 0.12)-induced ECAR increase was significantly smaller (p < 0.01) than that for ADP (3.64 ± 0.18), 2MeSATP (3.56 ± 0.02) and 2MeSADP (3.65 ± 0.13). The selective P2Y1 receptor antagonists A3′P-5′P and A3′P-5′PS inhibited the increase in ECAR-induced by ADP. Clamping [Ca2+]i with BAPTA (30 and 50 µmol/l) led to inhibition of ADP-induced increase in ECAR. Agonist and antagonist data indicate P2Y1 activation leads to a [Ca2+]i-dependent acidification of the extracellular medium.
The cAMP Pathway Sensitizes VR1 Expressed in Oocytes from Xenopus laevis and in CHO Cells
Authors: Vulcu Sebastian D. , Rupp Johanna , Wiwie Caroline , Gillen Clemens , Jostock Ruth , Nawrath Hermann
Published: July 2003

The vanilloid receptor 1 (VR1) is a heat-activated cation channel which also responds to capsaicin and other chemical stimuli. Protein kinase C has a stimulatory effect on VR1 activity, either alone or after activation with capsaicin. The influence of the cAMP-signaling pathway on the effects of capsaicin is controversial. To clarify this, the actions of capsaicin and the modulatory effects of forskolin, pCPT-cAMP, and isobutylmethylxanthine were studied in Xenopus laevis oocytes expressing rat VR1 and in CHO cells expressing human VR1. Capsaicin activated the VR1 channel and increased the intracellular calcium concentration. The effects of capsaicin were enhanced by forskolin, pCPT-cAMP, and isobutylmethylxanthine. A modulatory function of the cAMP system on VR1 activation could, therefore, modulate heat sensation and pain.
Effects of Camonagrel, a Selective Inhibitor of Platelet Thromboxane Synthase, on the Platelet-Subendothelium Interaction
Authors: Villalobos M.A. , De La Cruz J.P. , Escalante R. , Arrebola M.M. , Guerrero A. , Sánchez de la Cuesta F.
Published: July 2003

The aim of this study was to compare the effects of a new thromboxane synthase inhibitor, camonagrel, on platelet aggregation and platelet-subendothelium interaction under flow conditions, in comparison with a standard thromboxane synthase inhibitor (dazoxiben) and a cyclooxygenase inhibitor (acetylsalicylic acid). With respect to platelet aggregation in whole blood, the 50% inhibitory concentrations (IC50) of camonagrel were between 318 and 797 µmol/l after induction with collagen and adenosine 5′-diphosphate, respectively. For inhibition of thromboxane B2 synthesis, the IC50 values were 868 ± 68 µmol/l; prostaglandin E2 was inhibited only by acetylsalicylic acid (IC50 for camonagrel >2,000 µmol/l), and the leukocyte 6-keto-PGF1α level was increased by camonagrel. The greatest reduction in percentage subendothelial surface occupied by platelets (mainly in the thrombi) after blood perfusion was seen after incubation with camonagrel in the range of concentrations that inhibited collagen-induced platelet aggregation. In conclusion, camonagrel reduced platelet-subendothelium interaction under flow conditions, showing this effect in a range of concentrations lower than in inhibition of platelet aggregation.
Effects of RS-601, a Novel Leukotriene D4/Thromboxane A2 Dual Receptor Antagonist, on Asthmatic Responses in Guinea Pigs
Authors: Yamada Takatoshi , Takahashi Yoshimasa , Ishizaki Masayuki , Musoh Keiichi , Ohashi Tetsuo , Tanaka Hiroyuki , Inagaki Naoki , Nagai Hiroichi
Published: July 2003

The effects of 4-[4-[5,5,6,6,6-pentafluoro-1-(4-fluorobenzene-sulfonamido)hexyl]phenyl]butyric acid (RS-601), a novel leukotriene D4 (LTD4)/thromboxane A2 (TxA2) dual receptor antagonist, on bronchial asthmatic responses in guinea pigs were examined. The effects were compared with those of pranlukast (LTD4 receptor antagonist) and S-1452 (TxA2 receptor antagonist). RS-601 inhibited the increase in airway resistance caused by LTD4 and TxA2 mimetic compound, U-46619, but not by histamine. RS-601 and pranlukast but not S-1452 inhibited an antigen-induced late asthmatic response. In addition, RS-601 inhibited an antigen-induced airway hyperresponsiveness (AHR), whereas pranlukast and S-1452 had no effect on the AHR. The antigen-induced increase in inflammatory cells in airway was not affected by all examined agents. Furthermore, bacterial lipopolysaccharide-induced AHR in guinea pigs was clearly suppressed by RS-601 but not by pranlukast and S-1452. The increase in airway inflammatory cells caused by lipopolysaccharide was not affected by all three drugs. These findings indicate that RS-601 has a potent antiasthmatic efficacy, especially on AHR, but does not affect accumulation of eosinophils in the airways.
Estradiol Relaxes Rat Aorta via Endothelium-Dependent and -Independent Mechanisms
Authors: Abou-Mohamed Gamal , Elmarakby Ahmed , Carrier Gerald O. , Catravas John D. , Caldwell Robert W. , White Richard E.
Published: July 2003

The effects of estrogen on arterial function are heterogeneous with respect to vessel and/or species. We have investigated 17β-estradiol-induced relaxation in isolated rat aorta with regard to the role of the vascular endothelium and ionic mechanisms. Estrogen induced a concentration-dependent relaxation of 46.5 ± 7.9% and 70.1 ± 12.2% (10–8 and 10–7M), which was reduced by endothelial denudation. Furthermore, L-nitroarginine methyl ester completely abrogated this effect; however, estradiol did not relax KCl-contracted rings. Tetraethyl ammonium (1 mmol/l) completely blocked estradiol-induced relaxation. Estradiol increased [cGMP] in isolated aortic rings via NO, but did not significantly affect NOS activity in endothelial cells. Thus, estrogen can relax rat aorta in vitro via both endothelium-dependent and -independent mechanisms involving the NO/cGMP and potassium channel signaling system.
Nutritionally Regulated Hormonal Factors in Prolonged Postnatal Growth Retardation and Its Associated Adverse Neurodevelopmental Outcome in Extreme Prematurity
Authors: Yeung Melinda Y. , Smyth John P.
Published: July 2003

Recent published data show that at hospital discharge, most infants born at <30 weeks of gestation would not achieve the median birth weight of the reference fetus at the same postconceptional age, and many would be less than the 10th centile. Estimating from the current recommendations of calorie and protein intakes, these infants accrue large deficits in intakes of protein and calorie during the first weeks of life. Postnatal growth retardation over a prolonged period of time is related to neurodevelopmental delays. While a total energy intake of 120 kcal/kg/day has generally been considered adequate, protein requirement in low gestation infants remains a matter for debate. Increasing the dietary protein:calorie ratio has previously been proposed as a strategy to enhance growth and to achieve a body composition similar to that of the reference fetus. Previous study data reveal that serum insulin-like growth factor I (IGF-I) concentration is positively correlated with protein intake, and nitrogen retention, in turn, is positively correlated with serum IGF-I concentration. Remarkably, elevated serum growth hormone but low serum IGF-I concentrations have been reported in low gestation infants and in infants with intrauterine growth retardation, suggesting IGF-I being a nutritionally regulated hormonal factor in the postnatal growth retardation. As neurodevelopment in extreme prematurity is likely affected by multiple factors, we hypothesize that a combined strategy of the previously proposed hormonal supplement with hydrocortisone and tri-iodothyronine together with increased dietary protein intake (progressively increasing from 1.5 g/kg/day intravenously administered amino acids immediately after birth, then 3.6 g/100 kcal at ≈125 kcal/kg/day when enterally fed till the infant reaches a body weight of ≧1.8 kg and at ≧50th centile weight of the reference fetus at the same postconceptional age) would likely be synergistic and more effective in improving neurodevelopmental outcome.
Effects of Antenatal Antibiotics on the Incidence and Bacteriological Profile of Early-Onset Neonatal Sepsis
Authors: Laugel V. , Kuhn P. , Beladdale J. , Donato L. , Escande B. , Astruc D. , Messer J.
Published: July 2003

Background: Recommendations for the use of antenatal antibiotics have been widely implemented in the past few years, notably to prevent group B streptococcal disease or to prolong pregnancy in the case of preterm premature rupture of the membranes. Objectives: We designed a retrospective study to assess the potential effects of this increasing use of antibiotics on the incidence and bacteriological profile of early-onset neonatal sepsis (EONS). Methods: All neonates referred to our department for suspected EONS from January 1 1995 through December 31 1999 were included. Antenatal antibiotic exposure together with clinical and microbiological data from the neonatal period were gathered and analyzed on a yearly basis. Results: Of the 485 newborns who met the inclusion criteria, there were 101 cases of culture-confirmed sepsis; 339 cases of suspected sepsis and 69 cases of confirmed sepsis involved children born in the hospital, among a total of 16,627 live births registered in our center over the study period. The overall incidence of EONS dropped from 6.8 to 0.6/1,000 births between 1995 and 1999 (p < 0.001), but the rate of group B streptococcal infection decreased much more rapidly than that of non-group B streptococcal infection. We observed a trend towards the emergence of ampicillin-resistant Escherichia coli strains, which were isolated in seven cases. Among E. coli infections, ampicillin resistance was statistically linked with antenatal antibiotic use (p = 0.025). We also delineated several risk factors associated with these infections. Conclusion: In our center, antenatal antibiotic treatment was effective in reducing the incidence of EONS, but this benefit may come at the cost of favoring the emergence of ampicillin-resistant organisms causing severe neonatal infections. Antenatal and postnatal antibiotic treatment strategies should take this adverse effect into account.
Predictive Power of Initial Severity of Pulmonary Disease for Subsequent Development of Bronchopulmonary Dysplasia
Authors: Srisuparp Pimol , Marks Jeremy D. , Khoshnood Babak , Schreiber Michael D.
Published: July 2003

Using retrospectively acquired data from 138 mechanically ventilated premature infants, logistic regression was used to determine the relationships between the risk of bronchopulmonary dysplasia (BPD) and indices of initial respiratory disease severity [oxygen index (OI) and alveolar-arterial pO2 difference (A-a DO2)]. Indices were calculated from the first arterial blood gas analysis after initial surfactant administration. Infants were also classified as having mild [OI <4 cm H2O·mm Hg–1, A-a DO2 <150 mm Hg (20 kPa)] or severe [OI ≧10 cm H2O·mm Hg–1, A-a DO2 ≧300 mm Hg (40 kPa)] respiratory disease, and the ability of this classification to predict subsequent BPD risk was calculated. OI and A-a DO2 were significantly higher in the BPD group. Logistic regression analysis showed that BPD risk increased linearly with both OI (9%/cm H2O·mm Hg–1) and A-a DO2 [16%/50 mm Hg (16%/6.7 kPa)]. However, the predictive power (receiver-operator characteristic) of these models was modest. Unexpectedly, 29% of infants with mild initial disease developed BPD. These data suggest that, while BPD prediction in infants with severe disease is straightforward, the identification of those few infants with mild to moderate disease destined to develop BPD remains problematic.
Prevention of Candida Colonization Prevents Infection in a Neonatal Unit
Authors: Borderon J.C. , Therizol-Ferly M. , Saliba E. , Laugier J. , Quentin R.
Published: July 2003

This study represents a 1-year surveillance period using our epidemiology-based principles published and successfully followed since 1979: weekly culture for yeasts of oral and anal swabs, treatment with oral nystatin of all colonized newborns, and good hygiene/handwashing. Colonization was demonstrated in 23 out of 791 newborns admitted from October 1998 to September 1999. Twenty-two strains of Candida were identified: 16 C. albicans, 2 C. parapsilosis, 3 C. glabrata, and 1 C. tropicalis. Symptoms were erythema of the buttocks in 6 colonized newborns. No other culture positive for Candida could be found. Previous contamination was the main source (previous stay in an intensive care unit, rarely maternal origin). Contamination in the unit was unlikely. Eradication of Candida could be observed within 1 week. These good results, controversial in the literature, were obtained following epidemiological conclusions and support our guidelines.
Blood Volume Assessment with Hemoglobin Subtype Analysis in Preterm Infants
Authors: Leipälä Jaana A. , Talme Marjo , Viitala Juha , Turpeinen Ursula , Fellman Vineta
Published: July 2003

The aim of the study was to assess plasma volume (PV) and red cell volume (RCV) in preterm infants with a liquid chromatographic hemoglobin subtype method (HbST) based on dilution of autologous fetal hemoglobin (HbF) by donor adult hemoglobin and measurement of the amount of HbF. PV determination with the indocyanine green dye dilution technique (ICG) was used as a reference method. Eight infants, median gestational age 29.8 weeks (range 27.6–30.9 weeks) and median birth weight 1,300 g (range 1,030–1,760 g), were studied at a median age of 3.0 days (range 1–6 days). RCV was 33.6 ± 12 ml/kg measured with ICG and 32.1 ± 5.2 ml/kg with HbST. PV was 47.0 ± 18 and 40.2 ± 6.6 ml/kg, respectively. There was a close correlation between the RCVs measured with the two techniques (Pearson correlation 0.83, p < 0.05). In conclusion, HbST provides a reliable and safe determination of RCV in preterm infants.
Maternal Diet with Diverse Omega–6/Omega–3 Ratio Affects the Brain Docosahexaenoic Acid Content of Growing Chickens
Authors: Ajuyah A.O. , Wang Y. , Sunwoo H. , Cherian G. , Sim J.S.
Published: July 2003

Eggs with diverse ω–6/ω–3 ratio produced by feeding breeder hens a wheat-soybean meal-basal diet containing 5% (wt/wt) sunflower oil (Hω6), 5% fish oil (Hω3) or 2.5% sunflower oil plus 2.5% fish oil (Mω3ω6) were incubated. The hatched chicks were fed a docosahexaenoic acid (DHA)-deficient diet up to 6 weeks of age. The fatty acid composition of chick brain was determined on 0, 2, 4 and 6 weeks and brain weight was taken on day 0 and day 42. The ω–6/ω–3 ratios were 37.12, 4.21 and 0.98 for the maternal diet; 28.36, 2.83 and 0.89 for the egg yolk; 1.94, 0.48 and 0.18 for hatched chick brain (p < 0.05). At 2 weeks of age, the ω–6/ω–3 ratios were 1.88, 0.81 and 0.60 for chicks hatched from hens fed Hω6, Mω3ω6 and Hω3 diets, respectively. The brain DHA contents at 0 and 2 weeks of age were Hω3 > Mω3ω6 < Hω6 (p < 0.05) and at 4 and 6 weeks of age Hω3 = Mω3ω6 > Hω6. Dietary C18:3ω3 in the starter and finisher diet did not increase brain DHA (p > 0.05). The significant increase in the content of C22:5ω3 at 6 weeks of age in group 1 birds with a concomitant reduction in DHA suggests a weak delta-4 desaturation but an effective delta-6 and delta-5 desaturation similar to human infants. Considering the role of DHA in early brain development and growth, the maternal supply of DHA during growth might be of importance when fed a DHA-deficient neonatal diet.
Positive End-Expiratory Pressure Modulates Perfluorochemical Evaporation from the Lungs
Authors: Trevisanuto D. , Jeng M.J. , Weis C.M. , Fox W.W. , Wolfson M.R. , Shaffer T.H.
Published: July 2003

To study the effects of positive end-expiratory pressure (PEEP) level on perfluorochemical (PFC) elimination profiles (EL), 6 ml/kg of perflubron were instilled into healthy anesthetized rabbits. The ventilation strategy was to maintain constant minute ventilation (300 ml/kg/min) and mean airway pressure (7–8 cm H2O) while randomly changing the PEEP levels from 5 to 0, 1, 3, and 10 cm H2O, each for a period of 15 min. The PFC content in the expired gas was measured and the EL was calculated. There was a significant reduction in the EL when decreasing the PEEP levels from 5 to 0 cm H2O, but no differences were seen when the PEEP was increased from 5 to 10 cm H2O. The results indicate that PEEP levels influence PFC elimination profiles; therefore, the measurement of the EL and PEEP levels should be considered when optimizing supplemental PFCs during partial liquid ventilation.
Ontogenetic Expression of Estrogen and Progesterone Receptors in the Mouse Lung
Authors: Beyer Cordian , Küppers Eva , Karolczak Magdalena , Trotter Andreas
Published: July 2003

In the mammalian lung, estrogen and progesterone seem to be import for the morphological and functional maturation. Despite this, only sparse information is available on the onset and ontogenic expression of estrogen receptors (ER) and progesterone receptors (PR) in the perinatal lung. The expression patterns of the two known nuclear isoforms ER-α and ER-β and the PR were analyzed in the pre- and postnatal lungs of BALB/c mice. Steroid receptor mRNA expression of all three receptors were highest in the prenatal lung and declined thereafter to significantly lower levels in the postnatal and adult lung. The ontogenetic pattern of ER and PR expression supports the view that both gonadal steroids are pivotal for prenatal lung maturation and development.
Prolonged Mechanical Ventilation Induces Pulmonary Inflammation in Preterm Infants
Authors: Schultz Christian , Tautz Juliane , Reiss Irwin , Möller Jens Christian
Published: July 2003

Lung inflammation plays an important role in the pathogenesis of chronic lung disease in preterm infants. To test the hypothesis that prolonged mechanical ventilation induces pulmonary inflammation, we analyzed pro- and anti-inflammatory mediators in bronchoalveolar lavage fluid obtained from ventilated preterm infants having respiratory distress syndrome. Our results show a strong correlation between the duration of mechanical ventilation and the amount of proinflammatory mediators. However, the anti-inflammatory cytokine interleukin 10 remained stable during the whole period of mechanical ventilation. These data support the hypothesis that prolonged mechanical ventilation contributes to the development of chronic lung disease by the induction of lung inflammation without adequate stimulation of the counterregulatory cytokine interleukin 10 in preterm infants with respiratory distress syndrome.
Maternal and Umbilical Cord Serum Leptin Concentrations in Small-for-Gestational-Age and in Appropriate-for-Gestational-Age Neonates: A Maternal, Fetal, or Placental Contribution?
Authors: Grisaru-Granovsky S. , Eitan R. , Algur N. , Schimmel M.S. , Diamant Y.Z. , Samueloff A.
Published: July 2003

Leptin is secreted during pregnancy by the placenta and by the maternal and fetal adipose tissues. The leptin levels mainly reflect the amount of fat stored and thus are indicative of the energy balance, i.e., small-for-gestational-age (SGA) neonates represent the negative metabolic balance of in utero starved babies. We chose to compare maternal and umbilical cord leptin levels in pregnancies complicated by asymmetrical SGA versus those with appropriate-for-gestational-age (AGA) neonates as well as a model of multifetal growth concordant gestations in order to establish through the ‘leptin link’ the relative contributions of mother, fetus, and placenta to fetal weight. We found that the maternal leptin levels at delivery correlated poorly with the maternal weight gain/body mass index and with neonatal birth weight. Furthermore, the umbilical cord leptin levels correlated well with neonatal and placental weights in the AGA group but not in the SGA group. As in AGA singleton pregnancies, in multifetal uncomplicated pregnancies, the umbilical cord leptin levels correlated well with the birth weight of individuals, regardless of the status of the twin or triplet in the set. Thus, we speculated that in SGA neonates the birth weight represents the lean body weight and the low adipose tissue content (as opposed to the AGA neonates who have a substantial adipose tissue content) and, therefore, reflects mainly the basic placental contribution.
Transient Expression of Human Herpesvirus-8 (Kaposi’s Sarcoma-Associated Herpesvirus) ORF50 Enhances HIV-1 Replication
Authors: Caselli Elisabetta , Galvan Monica , Cassai Enzo , Di Luca Dario
Published: July 2003

Objective: Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi’s sarcoma, the most common neoplasm in patients with acquired immunodeficiency syndrome. Current evidence indicates that activation of viral replication may be critical to the development of the disease. A key factor in the induction of HHV-8 lytic replication is ORF50, an immediate-early gene encoding a transactivating protein necessary for viral reactivation. We recently reported that ORF50 synergizes with HIV-1 tat at a post-transcriptional level. To study the effects of these molecular interactions upon HIV replication and biology, cell lines of different origin were transiently transfected with ORF50 and subsequently infected with HIV. Methods: Jurkat, BCBL-1 and A172 cells were transfected with ORF50 and subsequently infected with different MOI of HIV. The development of infection was evaluated by analyzing p24 antigen release, production of infectious HIV particles and the presence and transcription of HIV proviral DNA. Results: ORF50 induced increased levels of HIV replication and production in CD4+ Jurkat T cells. Transfection of ORF50 into nonsusceptible B and glial cells (BCBL-1 and A172, respectively) increased cell susceptibility to infection and resulted in transient permissiveness to HIV replication. Conclusions: HIV replication can be significantly affected by the presence of HHV-8. Expression of ORF50 increases the efficiency of HIV infection in different cell types. This potentially could result in enhanced HIV spread within the infected organism and faster progression of the disease.
Analysis of Background Factors and Evaluation of a Population at High Risk of Hepatocellular Carcinoma
Authors: Miyazawa Kouji , Moriyama Mitsuhiko , Mikuni Morio , Matsumura Hiroshi , Aoki Hiroshi , Shimizu Toshihiro , Yamagami Hiroaki , Kaneko Miki , Shioda Atsuo , Tanaka Naohide , Arakawa Yasuyuki
Published: July 2003

Objective: We investigated the background clinical factors of patients with hepatocellular carcinoma (HCC) diagnosed at our institute and, from these results, determined those factors important for evaluation of a population at high risk of HCC. Methods: This study comprised 250 patients diagnosed with HCC from 1990 through 1995 in the Nihon University Itabashi Hospital. Background clinical factors, such as the results of blood chemistry at the time of the first angiography, were examined. Results: Markers of viral hepatitis in the 250 cases were as follows: type B (B-HCC), 29 (11.6%), type C (C-HCC), 201 (80.4%); type B+C, 3 (1.2%), and non-B, non-C (NBNC-HCC), 17 (6.8%). Approximately 35% of B-HCC and NBNC-HCC cases, but only 6% of C-HCC cases, exhibited platelet counts (PLT) equal to or more than 200,000/ml. On the other hand, 56.5% of the C-HCC cases exhibited PLT less than 100,000/ml, in contrast to less than 30% of the B-HCC and NBNC-HCC cases. Irrespective of the etiology of HCC, male sex and a history of smoking were characteristic risk factors. The percentages of abnormal results in combinations of tests in the B-HCC, C-HCC and NBNC-HCC subsets were: 69, 97 and 70% in the aspartate aminotransferase (AST) + PLT group (group A); 83, 98 and 70% in the group A + alanine aminotransferase (ALT) group (group B), and 86, 98 and 100% in the group B + γ-glutamyl transpeptidase (γ-GTP) group (group C), respectively. When hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCV-Ab) were also taken into account, abnormal results were found in every case in all of the HCC groups. Conclusion: C-HCC was found predominantly in cases with liver cirrhosis, whereas B-HCC and NBNC-HCC were observed more frequently in cases without liver cirrhosis. Testing for HBsAg and HCV-Ab, in addition to AST, ALT, PLT and γ-GTP, is considered necessary when screening for HCC.