bluuebunny/crossref_metadata_2025 huggingface dataset:
Steroid Sensitive Sites in the Avian Brain: Does the Distribution of the Estrogen Receptor α and β Types Provide Insight into Their Function?
Authors: Ball Gregory F. , Bernard Daniel J. , Foidart Agnès , Lakaye Bernard , Balthazart Jacques
Published: April 2003

Studies in avian species have often been useful in elucidating basic concepts relevant to the regulation of reproductive behaviors by sex steroid hormones. Once a link between a steroid hormone and a behavioral response has been established, one can use the localization of steroid hormone receptors in the brain to facilitate the identification of neural circuits that control behavior. The recent identification of a second type of estrogen receptor called estrogen receptor β or ERβ has raised new issues about the action of steroid hormones in the brain. A hypothesis has been proposed by Kuiper et al. [1998] based on studies in mammalian species suggesting that ERα (the name given to the ER that was previously described) is important for reproduction while ERβ is more important for non-reproductive functions. In this paper we apply this hypothesis more generally by examining possible functions of ERβ in avian species. We have initiated studies of the ERβ in the brain of two avian species, the Japanese quail (Coturnix japonica) and the European starling (Sturnus vulgaris). ERβ was cloned in both species and the mRNA for this receptor type was localized in the brain employing in situ hybridization histochemistry methods. In both species ERβ was found to be diffusely present in telencephalic areas consistent with a role for this receptor subtype in cognitive functions. However, ERβ mRNA was also found in many brain areas that are traditionally thought to be important in the regulation of reproductive functions such as the preoptic region, the bed nucleus of the stria terminalis and the nucleus taeniae. Of the two receptor types, only mRNA for ERα was observed in the telencephalic vocal control nucleus HVc of male starlings. Steroid receptors in this nucleus are thought to be an example of an evolutionary specialization that has evolved to coordinate the production of courtship vocalizations with other aspects of reproduction. The lack of ERβ mRNA expression in HVc is consistent with the hypothesis that ERα is preferentially involved in reproductive behaviors while ERβ is involved in the steroid regulation of other neural functions. However, the widespread occurrence of ERβ in other nuclei involved in reproductive function suggests that one must be cautious about the general applicability of the above hypothesis until more is known about ERβ function in these other nuclei.
Steroid Hormones Use Non-Genomic Mechanisms to Control Brain Functions and Behaviors: A Review of Evidence
Authors: Moore Frank L. , Evans Simon J.
Published: April 2003

Progestins, estrogens, androgens, and corticosteroids are capable of modifying brain functions and behaviors by mechanisms that involve the classic genomic model for steroid action. However, experimental evidence indicates that some responses to steroid hormones use non-classical, non-genomic mechanisms. This paper reviews the evidence that steroids can bind to receptors in the plasma membrane, activate cell signaling pathways, and regulate responses on a time scale of seconds or a few minutes. The existence of these alternative regulatory pathways for steroid hormones should make endocrinologists and neurobiologists change how they think about steroid hormones. It is no longer valid to assume that minute-to-minute changes in steroid concentrations are not regulating biologically important, short-term responses, or that the only steroids with biological functions are the ones that bind with high affinity to intracellular steroid receptors.
Nitric Oxide Synthase Expression in the Opossum Superior Colliculus: A Histochemical, Immunohistochemical and Biochemical Study
Authors: Giraldi-Guimarães Arthur , Tenório Frank , Brüning Gerold , Mayer Bernd , Mendez-Otero Rosalia , Cavalcante Leny A.
Published: April 2003

The expression of neuronal nitric oxide synthase (nNOS) in the superior colliculus (SC) of the opossum Didelphis marsupialis was studied by NADPH diaphorase (NADPH-d) histochemistry and nNOS immunohistochemistry. In addition, the activity of nNOS was quantified by measurement of [3H]-L-arginine conversion to [3H]-L-citrulline in tissue extracts from SC superficial layers in opossums and rats. Our results show that the number of NADPH-d stained cells was small and virtually identical in stratum opticum (SO) and stratum griseum superficiale (SGS) and their staining was very light, particularly in SGS. Neuropil staining was heavier in the stratum zonale (SZ) than in SGS or SO. The intermediate and deep layers contained heavily stained cells and moderate neuropil staining. Surprisingly, nNOS-immunoreactive cells were far more numerous than NADPH-d+ cells in every layer. The production of [3H]-L-citrulline from [3H]-L-arginine in tissue extracts enriched in superficial layers indicated that nNOS specific activity is as high in the opossum as in the rat. Our results suggest that the location of nNOS-expressing neurons in retino-receptive layers may be related to inter-specific differences in the processing of visual information.
Neural Connections of the Anterior Hypothalamus and Agonistic Behavior in Golden Hamsters
Authors: Delville Yvon , De Vries Geert J. , Ferris Craig F.
Published: April 2003

In male golden hamsters, offensive aggression is regulated by an interaction between arginine-vasopressin and serotonin at the level of the anterior hypothalamus. The present studies were conducted to study a neural network underlying this interaction. The connections of the anterior hypothalamus were examined by retrograde and anterograde tracing in adult male hamsters. Several limbic areas were found to contain both types of tracing suggesting reciprocal connections with the anterior hypothalamus. Their functional significance relating to the consummation of aggression was tested by comparing neuronal activity (examined through quantification of c-Fos-immunolabeling) in two groups of animals. Experimental animals were sacrificed after attacking an intruder. Control animals were sacrificed after exposure to a woodblock carrying the odor of an intruder that elicited behaviors related to offensive aggression without its consummation. An increased density of Fos-immunoreactivity was found in experimental animals within the medial amygdaloid nucleus, ventrolateral hypothalamus, bed nucleus of the stria terminalis and dorsolateral part of the midbrain central gray. These data suggest that these areas are integrated in a neural network centered on the anterior hypothalamus and involved in the consummation of offensive aggression. Finally, c-Fos-immunoreactivity was combined with labeling of serotonin and vasopressin neurons to identify sub-populations particularly associated with offensive aggression. Vasopressin neurons in the nucleus circularis and medial division of the supraoptic nucleus showed increased neuronal activity in the fighters, supporting their role in the control of offensive aggression.
Attractors: Architects of Network Organization?
Authors: Mpitsos George J.
Published: April 2003

An attractor is defined here informally as a state of activity toward which a system settles. The settling or relaxation process dissipates the effects produced by external perturbations. In neural systems the relaxation process occurs temporally in the responses of each neuron and spatially across the network such that the activity settles into a subset of the available connections. Within limits, the set of neurons toward which the coordinated neural firing settles can be different from one time to another, and a given set of neurons can generate different types of attractor activity, depending on how the input environment activates the network. Findings such as these indicate that though information resides in the details of neuroanatomic structure, the expression of this information is in the dynamics of attractors. As such, attractors are sources of information that can be used not only in adaptive behavior, but also to effect the neural architecture that generates the attractor. The discussion here focuses on the latter possibility. A conjecture is offered to show that the relaxation dynamic of an attractor may ‘guide’ activity-dependent learning processes in such a way that synaptic strengths, firing thresholds, the physical connections between neurons, and the size of the network are automatically set in an optimal, interrelated fashion. This inter-relatedness among network parameters would not be expected from more classical, ‘switchboard’ approaches to neural integration. The ideas are discussed within the context of ‘pulse-propagated networks’ or equivalently as ‘spike-activated networks’ in which the specific order in time intervals between action potentials carries important information for cooperative activity to emerge among neurons in a network. Though the proposed ideas are forward-looking, being based on preliminary work in biological and artificial networks, they are testable in biological neural networks reconstructed from identified neurons in cell culture and in simulation models of them.
Use of Spectral Turbulence Analysis for the Identification of Patients at High Risk for Ventricular Fibrillation and Sudden Death in Patients with Hypertrophic Cardiomyopathy
Authors: Englund Anders , Hnatkova Kate , Kulakowski Piotr , Elliot Perry M. , Malik Malek , McKenna William J.
Published: April 2003

Hypertrophic cardiomyopathy carries an increased risk of sudden death. The aim of the present study was to assess the predictive value of the signal-averaged ECG, analysed in the time domain and using a new method, spectral turbulence analysis, for the identification of high-risk patients. Two-hundred and forty-six patients with hypertrophic cardiomyopathy were studied. During a mean follow-up of 68 ± 17 months, 17 patients died suddenly. Patients with sudden death (SD) and/or a history of ventricular fibrillation (VF; n = 25) were compared to patients without SD/VF (n = 221) and to patients without any recognised risk factors for SD (n = 82). There were no differences in mean values of the time domain or spectral turbulence parameters analysed between patients in the SD/VF group and the patients without SD/VF or in the low-risk group. It is concluded that the clinical usefulness of the signal-averaged ECG, analysed in the time domain or as spectral turbulence analysis, is limited in identifying high-risk patients with hypertrophic cardiomyopathy.
Accuracy of Two-Dimensional Echocardiographic Planimetry of the Mitral Valve Area before and after Balloon Valvuloplasty
Authors: Shiran Avinoam , Goldstein Steven A. , Ellahham Samer , Mintz Gary S. , Pichard Augusto D. , Pinnow Ellen , Lindsay Jr. Joseph
Published: April 2003

The purpose of this study was to assess the accuracy of planimetry after percutaneous balloon mitral valvuloplasty (PBMV). The mitral valve area (MVA) was estimated in 34 patients before and after PBMV, using two-dimensional echocardiographic planimetry, Doppler pressure half-time (PHT), and the Gorlin formula. There was no significant difference in the correlation of planimetry and PHT before (r = 0.53, p = 0.001) and after PBMV (r = 0.56, p < 0.001). A similar correlation was found between planimetry and the Gorlin formula (r = 0.44, p = 0.01 before PBMV, r = 0.37, p = 0.03 after PBMV). The concordance between planimetry, PHT, and the Gorlin formula in classifying patients into mild, moderate, or severe mitral stenosis was not worse after PBMV. Planimetry-derived MVA was not less accurate after PBMV than before PBMV. However, the correlation between the two echocardiographic measurements and the Gorlin formula was only moderate.
Influence of Body Composition on Electrocardiographic Identification of Left Ventricular Hypertrophy in Adolescents
Authors: Sugita Seiko , Takada Kazuo , Hayano Jun-ichiro
Published: April 2003

We investigated the influence of body composition on electrocardiographic (ECG) detection of left ventricular (LV) hypertrophy in 894 high-school students. The percent body fat and LV mass were estimated by bioelectrical impedance and echocardiography, respectively. There was no significant difference in LV mass among subjects classified according to the percent body fat. The cutoff ECG amplitudes (RV5 and SV1+RV5) for detection of LV hypertrophy (LV mass ≥90th percentile in both boys and girls) with 90% specificity were highest in the low-fat group and lowest in the high-fat group. When the effects of the percent body fat on ECG amplitudes were taken into account, the sensitivity of the ECG for detection of LV hypertrophy improved from 32.7 to 38.2% in boys; however, no improvement was observed in girls (from 33.3 to 30.6%). Evaluation of the percent body fat may improve the efficacy of ECG detection of LV hypertrophy in adolescent boys, but the usefulness of this method may be limited in girls.
Effects of Losartan Titrated to Losartan/Hydrochlorothiazide and Amlodipine on Left Ventricular Mass in Patients with Mild-to-Moderate Hypertension
Authors: Martina B. , Dieterle T. , Weinbacher M. , Battegay E.
Published: April 2003

To study the effects of the angiotensin II receptor antagonist Losartan and Amlodipine on left ventricular mass (LVM), we performed blood pressure measurements and transthoracic echocardiographies at baseline. After a 4-week placebo run-in period, 25 patients with mild-to-moderate essential hypertension were randomly allocated to active treatment with Losartan 50 mg titrated to Losartan 50 mg/hydrochlorothiazide (HCT) 12.5 mg (n = 11) or Amlodipine 5 mg titrated to 10 mg (n = 14) for 16 weeks. After treatment, blood pressure decreased significantly in both groups. LVM and LVM index (mean ± SD/median) in the Losartan group at baseline were 311 ± 101/288 g and 163 ± 55/150 g/m2 and decreased significantly to 252 ± 25/255 g and 133 ± 22/128 g/m2 (p = 0.003 for LVM; p = 0.01 for LVM index) after 16 weeks of active treatment. In the Amlodipine group LVM and LVM index decreased from 259 ± 47/243 g and 136 ± 25/ 131 g/m2 to 240 ± 42/234 g and 126 ± 24/123 g/m2 (n.s.). In conclusion, LVM decreased significantly as early as 16 weeks after initiation of antihypertensive treatment with the Angiotensin II antagonist Losartan.
Plasma Apolipoprotein B Levels Predict Platelet-Dependent Thrombosis in Patients with Coronary Artery Disease
Authors: Shechter Michael , Bairey Merz C. Noel , Paul-Labrador Maura J. , Shah Prediman K. , Kaul Sanjay
Published: April 2003

Elevated plasma apolipoprotein B is a known risk factor for atherosclerotic coronary artery disease (CAD), however its relationship to arterial thrombosis is unexplored. We prospectively assessed apolipoprotein B and platelet-dependent thrombosis (PDT) in 42 CAD patients (37 men, 5 women, mean age 68 ± 9 years), by exposing porcine aortic media to their flowing unanticoagulated venous blood for 5 min using an ex vivo perfusion (Badimon) chamber. PDT was significantly correlated with apolipoprotein B (r = 0.41, p = 0.009), intracellular magnesium levels (r = –0.46, p = 0.003) fasting blood glucose (r = 0.47, p = 0.002), and total cholesterol (r = 0.43, p = 0.006). PDT did not correlate with serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-I or fibrinogen levels. These findings suggest that the positive relationship of elevated apolipoprotein B to CAD may be, in part, related to its prothrombotic effects.
Monitoring of Extracellular Aspartate Aminotransferase and Troponin T by Microdialysis during and after Cardioplegic Heart Arrest
Authors: Kennergren Charles , Mantovani Vittorio , Lönnroth Peter , Nyström Britta , Berglin Eva , Hamberger Anders
Published: April 2003

This study aims at developing per- and postopertive surveillance of the myocardium and focuses on ischemic damage following cardioplegic heart arrest. Levels of troponin T and total aspartate aminotransferase (ASAT) were analyzed in the myocardial interstitium of 10 patients with ischemic heart disease (IHD) who underwent coronary bypass surgery and in 12 patients with nonischemic heart disease (N-IHD) who underwent valvular surgery. Fluid from the myocardial interstitium of the anterior and the lateral wall of the heart was sampled by microdialysis probes that were implanted during surgery and extracted percutaneously 70–100 h later. There were no adverse reactions, and the equipment did not interfere with the surgical procedures. The peak in troponin T serum levels that occurred 4 h after cardiac arrest was preceded by a peak in troponin T levels in the microdialysates from the interstitium that occurred 1 h earlier. The concentration of troponin T in the microdialysate peak was 300 times higher than in the serum peak. The increase in serum ASAT levels during the first 7 h after cardiac arrest corresponded in time with a decrease in interstitial ASAT levels, which had already reached a maximum during cardiac arrest. The microdialysate/serum concentration ratio was considerably smaller for ASAT than for troponin T. Interstitial peak levels of troponin T correlated positively and significantly with peak levels of ASAT. Of the 22 patients, 15 had no postoperative events according to clinical outcome, ECG and serum tests. Fourteen of these had low to normal levels of interstitial ASAT and troponin T. Conversely, atrial fibrillation and/or premature atrial contractions were recorded in 8/22 patients, 7 of whom had elevated interstitial ASAT and/or troponin T concentrations in one or both of the sampled heart regions. The N-IHD patients had higher levels of troponin T in the interstitium 20–70 h following cardioplegia, while the peak levels did not differ between the groups. In conclusion, microdialysis sampling of troponin T and ASAT is safe and allows a highly sensitive analysis of the ischemic trauma exerted by the cardioplegic arrest.
A Case of Constrictive Pericarditis with Local Thickening of the Pericardium without Manifest Ventricular Interdependence
Authors: Hasuda Toshio , Satoh Toru , Yamada Naoaki , Sakamaki Fumio , Kyotani Shingo , Nakanishi Norifumi , Kosakai Yoshio
Published: April 2003

This is the first case report of postsurgical constrictive pericarditis confined to the left ventricle in which the majority of diagnosis tests were not indicative of the disease. A 50-year-old woman with a past history of mitral valve replacement was admitted for right heart failure. Cardiac catheterization showed impaired diastolic filling but lacked the characteristic ventricular interdependence recently reported to be specific for the disease, without manifest radiological appearance of pericardial thickening. However, a new technique using magnetic resonance tagging cine revealed pericardial adhesion, limited to the left ventricle, which was confirmed during pericardiectomy. After the surgery, right heart failure and diastolic filling abnormality disappeared with restoration of normal heart pressures.
Cardiac Dysfunction and Long-Term Prognosis in Patients with Nonobstructive Hypertrophic Cardiomyopathy and Abnormal 123I-15- (p-Iodophenyl)-3(R,S)-Methylpentadecanoic Acid Myocardial Scintigraphy
Authors: Shimizu Masami , Ino Hidekazu , Okeie Kazuyasu , Emoto Yorito , Yamaguchi Masato , Yasuda Toshihiko , Fujino Noboru , Fujii Hiroyuki , Fujita Shinichiro , Mabuchi Tomohito , Nakajima Kenichi , Taki Junichi , Mabuchi Hiroshi
Published: April 2003

To evaluate the relationship between myocardial scintigraphic abnormalities based on 123I-radioiodinated 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) uptake and cardiac function and the relationship between these abnormalities and long-term prognosis in patients with hypertrophic cardiomyopathy (HCM), 27 patients with nonobstructive HCM underwent BMIPP myocardial scintigraphic study, echocardiography, and exercise radionuclide study. Based on the extent of BMIPP scintigraphic defects, the patients were divided into two groups: Group A (n = 19) patients had no or small defects, and group B (n = 8) patients had moderate to large defects. Cardiac events were recorded over an average period of 64 months. The left ventricular end-diastolic and end-systolic dimensions were significantly greater in group B than in group A. The fractional shortening in group B was less than in group A (p = 0.0002). The BMIPP score and fractional shortening at rest correlated significantly (p < 0.05). The BMIPP score and the change in ejection fraction between rest and peak exercise correlated significantly (p < 0.05). While only 1 cardiac event occurred in the 19 patients in group A during a mean follow-up period of 64 months, 6 cardiac events occurred in the 8 patients in group B. The 84-month event-free survival rate was 94.4% in group A and 14.6% in group B (p < 0.01). These results suggest that patients with HCM and moderate to large defects as assessed by BMIPP myocardial scintigraphy have decreased cardiac function and a poor prognosis.
Increased Blood Vascular Endothelial Growth Factor Levels in Patients with Acute Myocardial Infarction
Authors: Ogawa Hisao , Suefuji Hisakazu , Soejima Hirofumi , Nishiyama Koichi , Misumi Kenji , Takazoe Keiji , Miyamoto Shinzo , Kajiwara Ichiro , Sumida Hitoshi , Sakamoto Tomohiro , Yoshimura Michihiro , Kugiyama Kiyotaka , Yasue Hirofumi , Matsuo Katsuhiko
Published: April 2003

Vascular endothelial growth factor (VEGF) is a growth factor for vascular endothelial cells in vitro. The present study was designed to determine whether serum VEGF levels increase in patients with acute myocardial infarction (AMI) compared with patients with stable exertional angina and control subjects, and to examine the serial changes of serum VEGF levels in patients with AMI. We examined serum VEGF levels by using antibody prepared from serum immunized with human VEGF121. The serum VEGF level (pg/ml) was higher (p < 0.0001) on admission in the patients with AMI (177 ± 19) than in those with stable exertional angina (61 ± 7) and control subjects (62 ± 6). The serum VEGF level (pg/ml) of the patients with AMI was 177 ± 19 on admission, 125 ± 9 on day 3, 137 ± 11 on day 5, 242 ± 18 at 1 week, and 258 ± 22 at 2 weeks after admission. The value was higher on admission than on day 3 after admission (p = 0.014), the values were higher at 1 week and 2 weeks than on admission, on day 3, and 5 (p < 0.01). Furthermore, there were correlations between peak VEGF levels at 1 week or 2 weeks after admission and peak creatine kinase levels. The increase of VEGF on admission in the patients with AMI may be due to the hypoxia of acute myocardial ischemia. The elevation at 1 week and 2 weeks from the onset may cause the development of collateral circulation in relation to the healing of the infarction site.
Cardiac Involvement in Primary Myopathies
Authors: Finsterer J. , Stöllberger C.
Published: April 2003

Simultaneous or temporarily staggered affection of both the skeletal as well as the cardiac muscle (cardiac involvement, CI) is a frequent finding in primary myopathies (MPs). CI leads to impulse generation defects, impulse conduction defects, thickened myocardium, left ventriculalr hypertrabeculation, dilatation of the cardiac cavities, secondary valve insufficiency, reduction of coronary vasodilative reserve, intracardial thrombus formation, and heart failure with systolic and diastolic dysfunction. CI has been found in Duchenne muscular dystrophy (MD), Becker MD, Emery-Dreifuss MD, facioscapulohumeral MD, sarcoglycanopathies, myotubular congenital MD, myotonic dystrophies type 1 and 2, proximal myotonic myopathy, myoadenylate deaminase deficiency, glycogenosis type II, III, IV, VII and IX, carnitine deficiency, mitochondriopathy, desmin MP, nemaline MP, central core disease, multicore MP, congenital fiber-type disproportion MP, Barth syndrome, McLeod syndrome and Bethlem MP. Patients with any of the above-mentioned myopathies should be cardiologically investigated as soon as their diagnosis is established, since sufficient cardiac therapy improves CI in MPs and since management of these patients is influenced by the degree of CI.
Early Reperfusion Assessment and Repeated Thrombolysis in Acute Myocardial Infarction Estimated by Repeated Standard Electrocardiography
Authors: Gill Sabine , Haastrup Benedikte , Haghfelt Torben , Dellborg Mikael , Clemmensen Peter M.
Published: April 2003

Thrombolytic therapy with streptokinase (SK) in acute myocardial infarction (AMI) does not result in early reperfusion in approximately 25% of patients. We hypothesized that early repeated thrombolysis with rt-PA in patients with early failed reperfusion would result in myocardial reperfusion. Fifty-nine AMI patients with a symptom delay of <6 h, treated with SK were included. ECG was taken on admission and after 90 and 180 min. An ST recovery of ≥25% at 90 min was interpreted as successful reperfusion. Sixteen patients had failed reperfusion at 90 min and were randomized to repeated thrombolysis with rt-PA or placebo. At 180 min from SK start, ST recovery was higher in the placebo group than in the rt-PA group (71 vs. 40%, p = 0.05). No serious bleeding complications were observed. Due to the limited sample size it was not possible to draw prominent conclusions.
Transurethral Prostatectomy in Patients with Preoperative Bacteriuria: Double-Blind Study with Oral Fleroxacin and Cefalexin
Authors: Viitanen Jouko , Malminiemi Kimmo , Kallio Jukka , Puolakka Veli-Matti , Rajala Pertti , Tammela Teuvo L.J.
Published: April 2003

We compared oral fleroxacin and cefalexin in the prevention of postoperative infectious complications after transurethral prostatectomy (TURP) in patients with preoperative bacteriuria. 95 patients underwent TURP due to benign prostatic hyperplasia with preoperative bacteriuria . The therapy consisted of 7 days of oral fleroxacin 400 mg once a day or cefalexin 500 mg three times daily. After 2 weeks, 62% of the urine samples were sterile in the fleroxacin group but only 37% in the cefalexin group (p = 0.047). Patients in the cefalexin group had also statistically significantly more symptoms of urinary tract infections. After 6 weeks, the bacterial eradication rate was 53% in the fleroxacin group and 37% in the cefalexin group. There were no septicemias. TURP can be performed with reasonable safety with this oral anbiotic therapy.
Therapeutic Effects of an Injectable New Quinolone, Pazufloxacin, against Polymicrobial Infections in the Uterine Endometritis Model
Authors: Mikamo Hiroshige , Kawazoe Kyoko , Sato Yasumasa , Tamaya Teruhiko
Published: April 2003

Polymicrobial infections with aerobes and anaerobes are common in female genital tract infections. We evaluated the efficacy of an injectable new quinolone, pazufloxacin, using a uterine endometritis model. Rats were infected with a mixed inoculation of Escherichia coli plus Bacteroides fragilis (MIC of pazufloxacin and ceftazidime: E. coli: 0.05 and 1.56 µg/ml, respectively, B. fragilis: 3.13 and 3.13 µg/ml, respectively). After inoculating 107 cfu/rat of each organism, pazufloxacin or ceftazidime (10 or 20 mg/kg, respectively, i.v., b.i.d., 3 days) was administered and compared with the nontreated group. The viable cell counts of the uterine corpus and uterine cervix in pazufloxacin-treated and ceftazidime-treated groups were decreased, compared with the nontreated group. The viable cell counts of the adnexa in the pazufloxacin-treated group were significantly decreased, compared with the ceftazidime-treated group. These results suggest that pazufloxacin would be useful for the treatment of polymicrobial infections, especially adnexitis.
Antifungal Activity of D0870 against Murine Infections and Its Mechanism of Action
Authors: Yamada Hidehiko , Tsuda Toshihiko , Watanabe Taiji , Kusakabe Satoshi , Mochizuki Hidenori
Published: April 2003

We evaluated the in vivo antifungal activity of D0870, a new triazole agent, in comparison with that of fluconazole in two murine infection models. The therapeutic mechanism of D0870 in these models was also investigated in vitro. In a pulmonary infection with Cryptococcus neoformans in immunosuppressed mice, D0870 at 10–100 mg/kg significantly reduced viable counts in lungs infected with C. neoformans to 1/10–1,000 of the control on day 14, whereas fluconazole, only at 100 mg/kg, showed a significant reduction in the viable counts and was less active than D0870 at 10 mg/kg. D0870 at 3–30 mg/kg also showed excellent therapeutic efficacy against murine vaginal candidiasis and completely eliminated viable yeasts from the vaginal cavity, whereas positive cultures were found in 20% of mice treated with 30 mg fluconazole/kg. At pH 7 and 37°C, D0870 was active against C. neoformans in synthetic amino acid medium, fungal or sabouraud dextrose broth. By reducing the pH of the medium, the in vitro anticryptococcal activity of D0870 was enhanced and found to be fungicidal under all culture conditions at pH 4–5. D0870 also showed a stronger fungistatic activity against Candida albicans at pH 4. These results suggest that D0870 may exhibit a potent activity against these two murine infections by exerting an excellent antifungal activity at the infection sites thought to be acidic environments.
Prospective Comparison of Ceftriaxone and Cefotaxime for the Short-Term Treatment of Bacterial Meningitis in Children
Authors: Scholz H. , Hofmann T. , Noack R. , Edwards D.J. , Stoeckel K.
Published: April 2003

The effectiveness and safety of ceftriaxone and cefotaxime in the short-term treatment of primary bacterial meningitis were compared using a prospective, randomized, multicenter study design. Children between the ages of 6 weeks and 16 years received either ceftriaxone as a single dose (100 mg/kg on the first day followed by 75 mg/kg/day) or cefotaxime as four divided doses (200 mg/kg/day) for 4–7 days. A total of 82 patients (44 ceftriaxone, 38 cefotaxime) with documented bacteria in the CSF were studied. In patients receiving ceftriaxone, full recovery occurred in 79.5% while a further 13.7% recovered with neurologic sequelae. Full recovery was observed in 71.1% of children treated with cefotaxime with sequelae in a further 23.6% (no statistically significant differences between drugs). The time to clinical improvement and resolution of fever (3–4 days) was also similar for both drugs. All but 1 of the 82 patients studied had negative CSF cultures within 24 h of the beginning of therapy consistent with the excellent penetration into the CSF (trough concentrations of 2.7 mg/l for both drugs at the end of therapy). No differences were observed in the incidence of clinically significant adverse events. Ceftriaxone and cefotaxime are both effective in the treatment of bacterial meningitis. Ceftriaxone offers an advantage in ease of administration since it is administered as a single daily dose.
Antibiotic Susceptibility of Stenotrophomonas (Xanthomonas) maltophilia: Comparative (NCCLS Criteria) Evaluation of Antimicrobial Drugs with the Agar Dilution and the Agar Disk Diffusion (Bauer-Kirby) Tests
Authors: Traub Walter H. , Leonhard Birgit , Bauer Dierk
Published: April 2003

Ninety-six clinical isolates of Stenotrophomonas maltophilia were examined with the agar dilution method for susceptibility to 19 antimicrobial drugs. Doxycycline, cotrimoxazole, timentin, ofloxacin, fosfomycin, and piperacillin + tazobactam, in that order, inhibited the majority of strains. All isolates were resistant to nitrofurantoin. Concurrent disk susceptibility (Bauer-Kirby method) testing, using currently valid NCCLS interpretative criteria for Pseudomonas aeruginosa, uncovered a significant incidence of very major (category I), major (category II), and minor (categories III and IV) discrepancies for aminoglycosides, cephalosporins, chloramphenicol, and piperacillin + tazobactam and ticarcillin + clavulanic acid. Therefore, new interpretative criteria indicative of intermediate (I) susceptibility of S. maltophilia to these various antibiotics were proposed. In addition, new intermediate susceptibility criteria were proposed for the two β-lactam-β-lactamase inhibitor combinations. It was recommended to exclude ciprofloxacin from test batteries against this microorganism due to the wide scatter of minimal inhibitory concentration values and diameters of inhibition zones; the same was true for polymyxin B. It is hoped that the proposed modified, species- specific criteria will improve the clinical utility of laboratory-generated disk antibiograms with respect to the inherently multiple antibiotic-resistant, opportunistic pathogen S. maltophilia.
Inhibition of Glycolysis and Respiration of Sarcoma-180 Cells by Echitamine Chloride
Authors: Saraswathi V. , Ramamoorthy N. , Subramaniam S. , Mathuram V. , Gunasekaran P. , Govindasamy S.
Published: April 2003

Malignant tumors are known to exhibit high rates of glycolytic activity leading to high production of lactic acid. Hence, neoplastic cells have elevated activity of enzymes responsible for glycolysis. Echitamine chloride, an indole alkaloid extracted from the bark of Alstonia scholaris, has been reported to have a highly promising anticancer activity against fibrosarcoma in rats. In the present study, the effect of echitamine chloride on energy metabolism of S-180 cells is investigated to have a better understanding on the mode of action of echitamine chloride. The effect of echitamine chloride on the mitochondrial and cellular respiration of S-180 cells was studied. Also, the effects on glucose utilization, pyruvate utilization and lactate formation were studied on whole S-180 cells and S-180 cell-free homogenate. The levels of glycolytic enzymes such as hexokinase and lactate dehydrogenase were estimated in which particular emphasis has been laid on hexokinase which occurs both in cytosolic and particulate forms in neoplastic cells. Hence the differential effect of echitamine chloride on the levels of total, cytosolic and particulate hexokinase has been investigated. In conclusion, echitamine chloride affects both cellular and mitochondrial respiration, leading to reduction of the cellular energy pool and thereby resulting in the loss of viability of S-180 cells.
Surveillance of Pseudomonas aeruginosa in Intensive Care Units: Clusters of Nosocomial Cross-Infection and Encounter of a Multiple-Antibiotic Resistant Strain
Authors: Traub Walter H. , Scheidhauer Ralf , Leonhard Birgit , Bauer Dierk
Published: April 2003

Serogrouping (determination of O antigens) and bacteriocin typing (based on susceptibility to one or more of 18 bacteriocins) were employed to survey 210 isolates of Pseudomonas aeruginosa from 201 patients in 8 intensive care units (ICU) during an observation period of 18 months. Eighty-eight isolates (41.9%) were nonserogroupable (NT); most common were serogroups O1, O9, O11, and O3. All except 5 isolates (97.6%) were bacteriocin-typable. However, phenotypic variation of bacteriocin susceptibility, in particular the receptor for bacteriocin No. 13, rendered this typing method presumptive as well. Bacteriocin susceptibility profiles were not predictive of serogroup and vice versa. Workup of 19 isolates from 9 patients disclosed phenotypic variation of antibiotic susceptibility in 3 patients, superinfection by a different strain in 4 patients, and persistence (3 months) of the same strain in 2 patients, respectively. Serotyping and bacteriocin susceptibility test data revealed 15 clusters of putative cross-infection of 2 patients each, 8 clusters involving 3 patients each, one outbreak (serogroup NT, bacteriocin profile 777736) involving 4 patients in the pediatric ICU, one outbreak due to a multiple-antibiotic resistant (MAR) strain in the surgical ICU (4 patients, serogroup O12, bacteriocin profile 30400), and two putative outbreaks in the pneumonology ICU involving 6 patients (serogroup NT, bacteriocin profile 777726) and 9 patients (serogroup NT, bacteriocin profile 777736). Pulsed-field gel electrophoresis (PFGE) macrorestriction analysis (SpeI, XbaI) confirmed the pediatric and surgical ICU strains as singular strains. However, the two putative outbreaks in the pneumonology ICU were due to one particular strain which had infected 13 of the 15 patients as determined with the PFGE genotypic method. Isolates comprising the MAR strain of P. aeruginosa were susceptible only to amikacin, fosfomycin, and polymyxin B; the isolates varied in susceptibility to aztreonam and ceftazidime. This MAR strain was susceptible to the bactericidal activity of 65 vol% of fresh defibrinated human blood from donors B, L, and T. Either amikacin (16 µg/ml) or fosfomycin (8 µg/ml) plus blood and amikacin (8 µg/ml) combined with fosfomycin (8 µg/ml) with and without blood consistently killed isolates of the MAR strain, which thus was amenable to antibiotic therapy.
In vitro Activity of Loracarbef against TEM Extended-Spectrum β-Lactamase-Producing Escherichia coli Strains andIts Interaction with the Enzymes
Authors: Prinarakis E.E. , Tzouvelekis L.S. , Legakis N.J.
Published: April 2003

The in vitro activity of loracarbef was evaluated against Escherichia coli strains producing TEM extended-spectrum β-lactamases (ESBLs). The MICs of loracarbef were lower than those of cefaclor and cephalothin. The antibiotic was active (MICs ≤2 mg/l) against strains producing TEM-6, TEM-8, TEM-10, TEM-16, TEM-26 and TEM-28 β-lactamases. The MICs for TEM-3-, TEM-5- and TEM-24-producing strains were higher (≥ 16 mg/l). Hydrolysis studies indicated that the latter β-lactamases inactivated loracarbef more efficiently than the remaining TEM-type ESBLs examined.
Effect of the 5α-Reductase Inhibitor PNU 156765, Alone or in Combination with Flutamide, in the Dunning R3327 Prostatic Carcinoma Model in Rats
Authors: Zaccheo Tiziana , Giudici Donata , Panzeri Achille , di Salle Enrico
Published: April 2003

The efficacy of treatment with the 5α-reductase inhibitor PNU 156765 (FCE 28260) was investigated in the Dunning R3327 prostatic tumor in rats. The compound, given orally at the doses of 10 and 50 mg/kg/day, for 8 weeks, reduced the growth of established tumors by 49–50%, an effect similar to that of flutamide at 5 mg/kg/day (46% inhibition). In a further experiment, the combination of PNU 156765 10 mg/kg/day and flutamide 5 mg/kg/day resulted in greater inhibition than either treatment alone (70 vs. 20% in PNU-156765-treated and 51% in flutamide-treated groups). The effect of the combination was similar to that of castration (75% inhibition). Ventral prostate weight was more markedly reduced by PNU 156765 than by flutamide, and combined treatment was as effective as castration. Prostatic dihydrotestosterone content was markedly reduced by PNU 156765 while prostatic testosterone increased. Concomitant treatment with flutamide antagonized the testosterone increase induced by PNU 156765. These data indicate a role for 5α-reductase inhibitors in the therapy of prostate cancer, in combination with antiandrogens, in order to achieve adequate androgen blockade with minimal side effects.
Bactericidal Effect of Levofloxacin on Strains with Equal Susceptibility in anin vitro Urinary Bladder Model
Authors: Takahashi Satoshi , Sano Masato , Nishimura Masahiro , Matsukawa Masanori , Mikami Midori , Hirose Takaoki , Tsukamoto Taiji
Published: April 2003

The in vitro bactericidal effects of therapeutic concentrations of levofloxacin (LVFX) on clinical isolates of Pseudomonas aeruginosa and Enterococcus faecalis were assessed. Starting from 107 CFU/ml, the bacterial count was determined serially during the exposure to LVFX present at concentrations automatically simulated to its clinically achievable urinary levels at the recommended dosage (100 mg 3 times daily). An isolate of P. aeruginosa for which the MIC of LVFX was 16 µg/ml was completely eradicated after 10 h of exposure to LVFX. On the other hand, 40 h of exposure to LVFX were required for complete eradication of an isolate of E. faecalis with equal susceptibility, although the bacterial count was rapidly reduced to 102 CFU/ml in the early phase of the exposure. It was concluded that LVFX exerts a more potent bactericidal effect on P. aeruginosa than on E. faecalis despite a similar susceptibility of these organisms to LVFX.
Erythromycin Resistance in Group A Beta Hemolytic Streptococcus
Authors: Esposito S. , Noviello S. , Ianniello F. , D’Errico G.
Published: April 2003

The incidence of erythromycin resistance and the phenotypic pattern of resistance have been studied in 130 group A β-hemolytic streptococcus (GABHS) strains, isolated from throat swab obtained in children affected by acute pharyngotonsillitis. A total of 56 (43%) GABHS strains of 130 were resistant to erythromycin. Among these 56 strains, we found that 7 (12.5%), 18 (32.1%) and 31 (55.3%) showed the cMLS, iMLS and M phenotype, respectively. The iMLS and M phenotypes appear to be the most widely represented ones. Their low level of resistance to macrolides could allow the use of the more recent macrolides characterized by higher tissue concentration which could overcome such a resistance.
Effects of Cefepime, Cefixime and Ceftibuten on Murine Gut Colonization by Candida albicans
Authors: Maraki S. , Barbounakis E. , Chatzinikolaou I. , Anatoliotakis N. , Plataki M. , Tselentis Y. , Samonis G.
Published: April 2003

Crl:CD1(ICR) BR mice were fed chow containing Candida albicans or regular chow. Both groups were subsequently given either antibiotics or normal saline. Stool cultures were performed before, at the end of treatment and 1 week after treatment, to determine the effect on the stool yeast concentration. Candida-colonized mice treated with cefepime, cefixime or ceftibuten had higher (however not significantly) counts of the yeast in their stools than control Candida-fed mice treated with saline. A group of Candida-fed mice were treated with ceftriaxone, which is known to increase the yeast stool concentration significantly and served as positive control. Mice fed regular chow and treated with the study drugs or saline did not have any yeasts in their stools. Dissemination of Candida did not occur.
Establishment and Characterization of Cisplatin-Resistant Human Epidermoid Carcinoma Cell Line, A431 Cell
Authors: Mese Hiroshi , Sasaki Akira , Alcalde Rafael E. , Nakayama Shuko , Matsumura Tomohiro
Published: April 2003

Cisplatin, cis-diamminedichloroplatinum(II) (CDDP) is one of the most important anticancer agents, initially producing good responses in various tumors. However, resistance to this drug often develops in various tumors, and additional administration decreases its chemotherapeutic efficacy. The precise mechanism of acquisition of resistance to this drug is still uncertain. However in the present study, we established two CDDP-resistant sublines A431/CDDP1 and A431/CDDP2 from human epidermoid carcinoma cell line A431. These resistant sublines were constituted by exposing A431 cells to a gradually increasing dose of CDDP (A431/CDDP1), and by mutagenic induction with mutagen (A431/CDDP2). A431/CDDP1 and A431/CDDP2 have developed 3.1 and 2.7 times more resistance to CDDP than the original A431 cell in terms of IC50. The two CDDP-resistant sublines showed cross-resistance to the CDDP analogue, carboplatin (CBDCA), but not to other chemotherapeutic drugs such as Adriamycin (ADR) and 5-fluorouracil (5-FU). These CDDP-resistant sublines were transplanted into nude mice to demonstrate the resistance to CDDP treatment in vivo. According to the in vitro assay, the mechanism of resistance in A431/CDDP1 and A431/CDDP2 seems to be based on a reduction of intracellular accumulation of CDDP, because their platinum concentration, which is the major component of CDDP, significantly declined. The established CDDP-resistant sublines may be used in further trials to improve the understanding of the mechanisms of resistance to CDDP.
Pharmacokinetics of Cefodizime in Patients with Various Degrees of Renal Failure
Authors: Loffreda A. , Lampa E. , Lucarelli C. , Amorena M. , Contaldi C. , Calderaro V. , Rossi F.
Published: April 2003

The pharmacokinetics of cefodizime, a new expanded-spectrum cephalosporin for parenteral use, was studied in 45 subjects with various degrees of renal failure. Patients were divided into five groups according to the following creatinine clearances: group I >80 ml/min; group II <80–30 ml/min; group III <30–15 ml/min; group IV <15–5 ml/min and group V <5 ml/min. Cefodizime was administered as a 1 g i.v. bolus. Plasma and urinary concentrations of cefodizime were determined by high-performance liquid chromatography, using for detection UV absorbance. The following pharmacokinetic parameters were calculated: maximum plasma concentration (C5 min), area under the plasma concentration-time curve (AUC), terminal half-life (T1/2), terminal rate constant (λ-z), total clearance (Clt), volume of distribution (Vd), mean residence time (MRT), urine data-derived terminal half-life (T1/2 r), renal clearance (Clr). The results of this study showed that renal failure induced changes in cefodizime pharmacokinetics. Our data demonstrated a close correlation between degree of renal impairment and pharmacokinetic changes. The maximum plasma concentration (C5 min) was higher in patients with renal failure; T1/2 was increased; AUC also increased from 470.40 ± 17.80 mg·h/l in the control group to 1,562.30 ± 170.8 mg·h/l in group V. Moreover, no side effect was observed after treatment with 1 g i.v. of cefodizime. Although renal failure induces significant changes of cefodizime pharmacokinetics, the drug was well tolerated and only in patients with severe renal insufficiency we advise to monitor the interval dose of cefodizime or adjust doses to renal function.
In vitro Activity of Trovafloxacin (CP 99,219), a New Fluoroquinolone against Hospital Isolates
Authors: Ling T.K.W. , Liu E.Y.M. , Cheng A.F.B.
Published: April 2003

The susceptibility of 492 Enterobacteriaceae, 227 other gram-negative bacteria, 448 gram-positive bacteria and 108 anaerobic organisms was determined by the agar dilution method against trovafloxacin and other antibiotics. Trovafloxacin was highly active against most of the Enterobacteriaceae including Enterobacter spp. and Citrobacter spp. [minimum inhibitory concentration (MIC)90 <1 mg/l], Acinetobacter spp. and Pseudomonas aeruginosa (MIC90 = 0.25 and 2 mg/l, respectively). The antimicrobial activity was extended to the gram-positive bacteria including streptococci, Streptococcus pneumoniae, coagulase-negative staphylococci and methicillin-sensitive Staphylococcus aureus with MIC90 <1 mg/l. Enterococci and methicillin-resistant S. aureus were inhibited (MIC90 = 2 mg/l; sparfloxacin and ciprofloxacin were 16 and 64 mg/l, respectively). Almost all anaerobic organisms were inhibited by trovafloxacin (MIC90 = 1 mg/l).
A New Fluoroquinolone Derivative Exhibits Inhibitory Activity against Human Immunodeficiency Virus Type 1 Replication
Authors: Kashiwase Hiroto , Momota Kenji , Ohmine Toshinori , Komai Tomoaki , Kimura Tomio , Katsube Tetsushi , Nishigaki Takashi , Kimura Satoshi , Shimada Kaoru , Furukawa Hidehiko
Published: April 2003

The inhibitory activity of several fluoroquinolone antibiotics against human immunodeficiency virus type 1 (HIV-1) replication was investigated. R-71762, (±) 9-fluoro-3-fluoromethyl-2,3-dihydro-10-[4-(2-pyridyl)-1-piperazinyl]-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, protected MT-4 cells from HIV-1-induced cytopathic effects. Furthermore, the compound inhibited virus replication both in acutely and in chronically HIV-1-infected cells. On the other hand, ofloxacin, levofloxacin, ciprofloxacin, norfloxacin and enoxacin, that were previously reported to be protective against HIV-1-induced cytopathic effects, did not show any protective activity in our assay system. These results indicate that R-71762 is a novel inhibitor of HIV-1 replication and is effective even in HIV-1 chronically infected cells.