bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Chronic Therapy with Proteolytic Enzymes on Hypertension-Induced Renal Injury in the Rat Model of Goldblatt Hypertension
Authors: Šebeková Katarina , Dämmrich Jobst , Fierlbeck Wolfgang , Krivosiková Zora , Pączek Leszek , Heidland August 
Published: April 2003

This study investigated the possible beneficial effect of intraperitoneal proteolytic enzyme administration on the development of hypertension-induced renal injury in the rat model of 2-kidney 1-clip (2K1C) Goldblatt hypertension. Male Wistar rats (120–150 g) underwent either sham surgery (control, n = 5) or clipping of the left renal artery. From day one 2K1C rats were randomized into 2 groups, placebo treatment (n = 7), and proteolytic enzyme treatment (n = 9). To the verum group a fixed mixture of trypsin (2.42 mg), bromelain (4.54 mg), and rutin (5.04 mg) dissolved in 2 ml of sterile 0.9% NaCl was administered intraperitoneally daily, while the placebo group received only vehicle. Rats were pair-fed. The duration of the study was 7 weeks. All 2K1C rats developed hypertension and the mean values of systolic blood pressure (SBP) did not differ significantly between the groups at any time recorded (SBP at sacrifice: controls 122.0 ± 8.5 mm Hg; placebo 191.4 ± 7.6 mm Hg; enzyme 180.5 ± 6.5 mm Hg). Enzyme treatment prevented the rise in proteinuria (controls 12.4 ± 2.6 mg/24 h; placebo 19.7 ± 3.9 mg/24 h; enzyme 12.2 ± 1.3 mg/24 h; p < 0.05) and ameliorated the increase in serum urea concentrations. Histomorphologically, signs of malignant nephrosclerosis were not found in control rats, while they were present in 4/7 (57%) of placebo-treated rats, but only in 1/9 (11%) of the enzyme-treated group. The volume fraction of renocortical interstitium was increased in both 2K1C groups in comparison with controls; however, enzyme treatment decreased the accumulation of interstitial tissue significantly (–22%) compared to placebo treatment. Cellular infiltration with mononuclear cells was also lower in the protease-treated group. To summarize, in the rat model of 2K1C hypertension, systemic treatment with proteases ameliorates the severity of nephrosclerosis and tubulointerstitial fibrosis in the non-clipped kidney, as well as proteinuria, without affecting high blood pressure.
Biochemical Parameters, Nutritional Status and Efficiency of Dialysis in CAPD and CCPD Patients
Authors: Gao Hubin , Lew SusieQ. , Bosch JuanP. 
Published: April 2003

<i>Background/Aims:</i> Several studies indicate that small solute transport is influenced by peritoneal dialysate volume and dwell time. This study focuses on the clinical impact of peritoneal dialysis modality, continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD). <i>Methods:</i> We studied 18 patients on CAPD and 11 on CCPD for 18 months and assessed biochemical parameters, nutritional status and efficiency of dialysis at 6-month intervals. <i>Results:</i> Four-hour D/P urea and creatinine ratios were similar in both CAPD and CCPD patients. However, 24-hour D/P urea and creatinine ratios were significantly higher in CAPD than in CCPD patients (0.9 ± 0.1 vs. 0.8 ± 0.2 and 0.8 ± 0.1 vs. 0.6 ± 0.2, p < 0.05 and p < 0.01, respectively). The dialysate urea nitrogen concentration was significantly different between the two groups (65 ± 14 mg/dl in CAPD, 48 ± 13 mg/dl in CCPD; p < 0.05). Total weekly Kt/V and total weekly creatinine clearance were not significantly different between CAPD and CCPD patients at 18 months (1.6 ± 0.4 vs. 1.7 ± 0.3 and 52 ± 21 vs. 50 ± 12 liters, respectively). Two-way ANOVA with a post-hoc Bonferroni-Dunn test showed serum potassium concentration was significantly lower in CCPD patients at 18 months (3.8 ± 0.5 mEq/l, p < 0.05), and significant increases in triglyceride levels in the CAPD groups by 18 months (301 ± 286 mg/dl, p < 0.05). <i>Conclusion:</i> This study demonstrates that the mean serum triglyceride level increases in CAPD patients over time, and the mean serum potassium concentration decreases in CCPD patients at 18 months. Dialysis adequacy and nutritional status are not significantly different between the two peritoneal dialysis modalities, CAPD and CCPD. We suggest the peritoneal dialysis prescription for CAPD or CCPD with respect to volume and frequency of exchanges be individualized to achieve adequate of therapy.
Serum Ionized Magnesium Levels in Type 2 Diabetic Patients with Microalbuminuria or Clinical Proteinuria
Authors: Corsonello Andrea , Ientile Riccardo , Buemi Michele , Cucinotta Domenico , Mauro Vittorio Nicita , Macaione Salvatore , Corica Francesco 
Published: April 2003

<i>Background/Aims:</i> The association between microalbuminuria and magnesium depletion is a controversial issue, and serum ionized magnesium levels have not been previously studied in patients with different grades of diabetic nephropathy. Therefore, the aim of this study was to evaluate circulating ionized magnesium concentrations in patients with non-insulin-dependent diabetes mellitus (NIDDM) and incipient or overt diabetic nephropathy. <i>Methods:</i> We measured fasting plasma glucose, creatinine, creatinine clearance estimate, total cholesterol and triglycerides, and serum ionized magnesium (ion-selective electrodes, ISE) in 30 NIDDM patients with urinary albumin excretion rate (UAER) <20 μg/min (normoalbuminuria), 30 NIDDM patients with microalbuminuria (20 < UAER < 200 μg/min), 30 NIDDM patients with clinical proteinuria (UAER >200 μg/min), and 20 healthy subjects. <i>Results:</i> Serum ionized magnesium levels were significantly reduced in diabetic patients when compared to control subjects (0.39 ± 0.06 vs. 0.58 ± 0.05 mmol/l, p < 0.001). Moreover, diabetic patients with microalbuminuria or clinical proteinuria showed a significant decrease in serum ionized magnesium with respect to normoalbuminuria group (normoalbuminuria: 0.45 ± 0.02 mmol/l; microalbuminuria: 0.36 ± 0.05 mmol/l, p < 0.001; clinical proteinuria: 0.35 ± 0.04 mmol/l, p < 0.001). Serum ionized magnesium showed a significant negative correlation with plasma HbA1c and triglycerides in both microalbuminuria and clinical proteinuria groups. Multiple linear regression analysis showed that circulating ionized magnesium levels decrease together with the increase of plasma HbA1c and triglycerides in NIDDM patients with incipient or overt nephropathy, also after adjusting for age, sex, BMI, diabetes duration, systolic and diastolic blood pressure, hypoglycemic therapy, plasma creatinine, creatinine clearance, plasma cholesterol and fasting glucose. <i>Conclusions:</i> Microalbuminuria and clinical proteinuria, as well as poor glycometabolic control and hypertriglyceridemia, are associated to relevant alterations in magnesium metabolism, and the measurement of serum ionized magnesium seems to represent a useful biochemical tool for the study of magnesium disturbances in patients with different grades of diabetic nephropathy.
Gene Transfer into Rat Renal Cells Using Adeno-Associated Virus Vectors
Authors: Shimpo Masahisa , Ikeda Uichi , Maeda Yoshikazu , Ueno Shuichi , Ikeda Michiyo , Minota Seiji , Takizawa Toshihiro , Urabe Masashi , Kume Akihiro , Monahan John , Ozawa Keiya , Shimada Kazuyuki 
Published: April 2003

Adeno-associated virus (AAV) vectors have a number of attractive features, including lack of cytotoxicity, ability to transduce nondividing cells, and long-term transgene expression. We investigated whether rat renal cells could be efficiently transduced with AAV vectors. Rat glomerular mesangial cells were transduced with AAV-lacZ vector containing β-galactosidase gene in vitro, and the expression of β-galactosidase was evaluated by X-gal staining and ELISA. For ex vivo experiments, sections of rat kidneys were incubated with AAV-lacZ, and then evaluated by X-gal histochemical staining. The level of β-galactosidase expression in cultured rat mesangial cells increased in a dose-dependent manner (ranging from 1 × 10<sup>5</sup> to 5 × 10<sup>6</sup> particles/cell). When transduced with 5 × 10<sup>6</sup> vector particles/cell of AAV-lacZ, about 50% of mesangial cells were stained positively with X-gal, and the level of β-galactosidase expression reached 9.9 ± 1.5 ng/mg protein. Expression was detectable during the culture period for at least 7 days. X-gal histochemical examination of the ex vivo transduced renal tissue revealed tubular cell and interstitial tissue staining. However, gene transfer was not clearly observed in glomeruli. These findings suggest that AAV vectors have the potential for gene therapy of renal diseases.
Predictors of the Development of Hyperkalemia in Patients Using Angiotensin-Converting Enzyme Inhibitors
Authors: Ahuja Tejinder S. , Freeman Jr. Daniel , Mahnken Jonathan D. , Agraharkar Mahendra , Siddiqui Mohammad , Memon Amir 
Published: April 2003

<i>Background/Aims:</i> Angiotensin-converting enzyme inhibitors (ACEI) are the antihypertensives of choice in patients with chronic renal failure (CRF). ACEI by decreasing the synthesis of aldosterone, the main regulator of serum potassium, predispose to the development of hyperkalemia. Although hyperkalemia with administration of ACEI is uncommon in patients with a normal renal function, a preexisting abnormality in potassium hemostasis, as seen in patients with chronic renal failure, may increase the risk of hyperkalemia. <i>Method:</i> To determine the predictors of development of hyperkalemia (K >5.1 mEq/l) in patients on ACEI, we retrospectively reviewed medical records of 119 patients followed in our renal clinic. <i>Results:</i> The mean age of the patients was 56 ± (SD) 13 (range 20–84) years. Sixty-three percent were males, and 37% were females. Sixty-seven percent had a history of diabetes. Eighty five percent of the patients had CRF [creatinine clearance (CrCl) <80 ml/min]. The baseline serum Cr was 2.3 ± 1.2 (range 0.6–6.9) mg/dl, and the CrCl was 50 ± 27.5 ml/min. Of the 119 patients 46 (38.6%) developed hyperkalemia (mean K 5.68 ± 0.3, range 5.2–6.7 mEq/l). Ninety-six percent of the patients who developed hyperkalemia had CRF, and 84% were diabetics. Pearson product-moment correlation revealed a significant positive correlation of hyperkalemia with Cr and a negative correlation of hyperkalemia with CrCl and HCO<sub>3</sub> (Cr: r = 0.42, p < 0.0001; CrCl: r = –0.34, p < 0.0001; HCO<sub>3</sub>: r = –0.41, p < 0.0001). Multivariate logistic regression analysis revealed diabetes and serum creatinine to be the main predictors of hyperkalemia. In 31 patients hyperkalemia resolved either with a low-potassium (2 g/day) diet or with diet and a decrease in the dose of ACEI. In 15 patients ACEI had to be discontinued due to persistent hyperkalemia. <i>Conclusions:</i> We conclude that hyperkalemia is common in patients with CRF on ACEI. The majority of the patients who develop hyperkalemia on ACEI have CRF and diabetes. A large number of patients with CRF require discontinuation of ACEI due to hyperkalemia and are deprived of their renoprotective effects.
Lactic Acidosis in the Setting of Antiretroviral Therapy for the Acquired Immunodeficiency Syndrome
Authors: Shaer Andrea J. , Rastegar Asghar 
Published: April 2003

Type B lactic acidosis, a rare but often fatal disorder, has been reported in 21 AIDS patients on antiretroviral therapy (ART). We present an AIDS patient with severe and prolonged lactic acidosis on stavudine and lamivudine. The lactic acidosis occurred in the absence of mitochondrial myopathy, hepatomegaly, or liver failure. This is the second report of lactic acidosis in a patient on stavudine and lamivudine. This patient recovered after aggressive supportive therapy including intravenous alkali and fluid administration as well as continuous venovenous hemodiafiltration. A single dose of dichloroacetate (DCA) was associated with a decrease in the serum lactate level by 20%, which persisted for more than 24 h. Seventeen months after recovery, the patient was rechallenged with ART without recurrence of lactic acidosis. We review and summarize all reported cases of patients with ART-associated lactic acidosis reported in the English literature.
Speech Sound Representation, Perception, and Plasticity: A Neurophysiologic Perspective
Authors: Kraus Nina , McGee Therese J. , Koch Dawn Burton 
Published: April 2003

Historically, auditory research has focused predominately upon how relatively simple acoustic signals are represented in the neuronal responses of the auditory periphery. However, in order to understand the neurophysiology underlying speech perception, the ultimate objective is to discover how speech sounds are represented in the central auditory system and to relate that representation to the perception of speech as a meaningful acoustic signal. This paper reviews three areas that pertain to the central auditory representation of speech: (1) the differences in neural representation of speech sounds at different levels of the auditory system; (2) the relation between the representation of sound in the auditory pathway and the perception/misperception of speech, and (3) the training-related plasticity of speech sound neural representation and speech perception.
Optical Imaging of Intrinsic Signals in Chinchilla Auditory Cortex
Authors: Harrison Robert V. , Harel Noam , Kakigi Akinobu , Raveh Eyal , Mount Richard J. 
Published: April 2003

We have assessed sound frequency and intensity responses in primary auditory cortex of the (ketamine) anesthetized chinchilla using optical imaging of intrinsic signals. Temporal cortex was exposed via a 10-mm craniotomy and a windowed chamber was mounted. A 4-second period of gated tones (10 ms rise/fall; 50 ms plateau; 10/s) was presented to the contralateral ear at levels between 0 and 80 dB SPL. The cortical surface was illuminated with 540 nm light and video images captured in 0.5-second bins for 7.5 s (Imager 2001; Optical Imaging). Intrinsic signals were first apparent 0.5–1 s after stimulus onset, and were maximal after 3–4 s; they decayed over several seconds. The cortical area in which intrinsic activity was detected corresponded closely with electrophysiologically defined AI cortex. Intrinsic signals can reliably be detected to stimuli at 30–40 dB SPL, and in general, the area of intrinsic signal activity tends to expand with increasing stimulation level. Using stimulation levels of 80 dB SPL, we show that low-frequency stimuli (0.5–1 kHz) evoke intrinsic signals in anterior areas whilst posterior areas are activated by high-frequency stimuli (e.g. 16 kHz). Thus a low- to high-frequency tonotopic organization is seen along this axis.
Presence of Tinnitus Indicated by Variable Spontaneous Otoacoustic Emissions
Authors: Ceranic Borka J. , Prasher Deepak K. , Luxon Linda M. 
Published: April 2003

Spontaneous otoacoustic emissions (SOAE) have been widely studied in normal subjects, and there is evidence of their high frequency stability in repeated recordings. A study to determine the frequency stability of SOAE in 53 of 100 consecutive patients, who presented with tinnitus and in whom SOAE were recordable, was undertaken. Patients were divided into five aetiologically homogeneous subgroups: (i) those with normal hearing and no identified pathology, (ii) those with sensorineural hearing loss of unknown origin, (iii) those with normal hearing, but complaining of tinnitus related to head injury, (iv) those with endolymphatic hydrops, and (v) those with noise exposure. The control group consisted of 20 subjects, selected on the basis of recordable SOAE from 38 volunteers with normal hearing and no tinnitus. The prevalence of SOAE and their inter-session frequency stability (reproducibility and relative frequency shift) were analysed. In contrast to the controls, the tinnitus group had significantly increased frequency variability of SOAE (lower reproducibility and increased relative frequency shift). The prevalence of subjects with SOAE was not notably different between the controls and subjects with tinnitus, if the tinnitus group was considered in toto, but a striking 100% prevalence of bilaterally present SOAE was observed in the tinnitus subgroup with head injury.
Serum C<sub>24</sub> Bile Acids in the Developing Human Fetus
Authors: Courillon Florence , Gerhardt Marie-Françoise , Myara Anne , Daffos Fernand , Forestier François , Trivin François 
Published: April 2003

The C<sub>24</sub> bile acids (BA) in the serum of 22 healthy human fetuses between weeks 20 and 37 of gestation were determined by capillary GC-MS. Fetal blood samples were taken in utero from the umbilical cord monitored by echography. There was no correlation between total bile acids (TBA) and gestational age. The TBA concentration was 5.14 ± 2.13 µ<i>M</i>. Primary BA (cholic acid and chenodeoxycholic acid) were the main BA (66.78 ± 13.47%) with chenodeoxycholic acid being the main one. There were low concentrations of secondary BA (deoxycholic acid and lithocholic acid) (10.28 ± 7.85%), which formed by intestinal bacterial 7α-dehydroxylation of primary BA in the adult, despite the germ-free gut. The tertiary BA (ursodeoxycholic acid) was also detected (12.06 ± 9.64%). There was 6α-hydroxylation of chenodeoxycholic acid and of lithocholic acid to produce hyocholic acid and hyodeoxycholic acid respectively. Two 1β-hydroxylated BA were detected at different times of gestation. Cholic acid was rarely found in the 6α- and 1β-hydroxylated forms. These additional hydroxylations could help to protect the fetal liver against the accumulation of cytotoxic bile acids at a time when other detoxification pathways are poorly developed. Traces of unsaturated bile acids like 3β-hydroxy-5-cholenoic acid were detected, showing that 27-hydroxylation of cholesterol does occur.
Effect of Phenobarbital on Bilirubin Metabolism in Rat Brain
Authors: Hansen Thor Willy Ruud , Tommarello Steve 
Published: April 2003

Bilirubin is metabolized by brain mitochondrial membranes. This activity increases with postnatal age, is higher in glia than in neurons, and is subject to genetic variability. The rates of oxidation are such that this mechanism probably contributes meaningfully to clearance of bilirubin from brain. Phenobarbital is a well-known inducer of bilirubin-metabolizing enzymes in the liver. Previous incomplete data had suggested that phenobarbital treatment might also affect bilirubin metabolism in brain. We studied the clearance of bilirubin from brain (branch 1) as well as the oxidation of bilirubin by brain mitochondrial membranes (branch 2) following pretreatment of young adult SPRD rats with phenobarbital 75 mg/kg i.p. daily for 7 days; controls received solvent only. On day 8, rats in branch 1 (n = 8 in both phenobarbital-treated and control groups) were anesthetized and 50 mg/kg bilirubin was infused i.v. over 5 min. Rats were sacrificed after 60 min and brain bilirubin determined by acid chloroform extraction. In branch 2 (n = 7 in both groups) rats were sacrificed with i.p. pentobarbital, brains were homogenized in 0.32 <i>M</i> sucrose and mitochondria separated out by differential centrifugation. The mitochondrial membrane suspension was added to a 10-µmol/l bilirubin solution, and the rate of bilirubin oxidation was measured at 440 nm. As expected following phenobarbital treatment, serum bilirubin was slightly lower in phenobarbital-treated vs. control rats [126 ± 32 vs. 140 ± 21 µmol/l (mean ± SD); p = 0.3]. Brain bilirubin values were also lower in the phenobarbital-treated rats (0.44 ± 0.06 vs. 0.52 ± 0.08 nmol/g, p = 0.044). As the lower brain bilirubin values in phenobarbital-treated rats could be due entirely to lower serum bilirubin values, we compared the brain:serum bilirubin ratios in the two groups. These were not different (0.0063 ± 0.0016 vs. 0.0064 ± 0011). The rate of bilirubin oxidation was significantly lower in phenobarbital-treated vs. control rats (256 ± 10 vs. 286 ± 26 pmol/min/mg protein, p = 0.023). We conclude that phenobarbital inhibits bilirubin metabolism in brain. However, albeit statistically significant, the difference is small and may not be biologically meaningful. Thus, pretreatment with phenobarbital had no effect on overall brain bilirubin clearance rate. We speculate that phenobarbital treatment may be neither helpful nor harmful relative to the neurotoxic effects of bilirubin in infants with already established jaundice.
A Single Dose of Antenatal Betamethasone Enhances Isoprenaline and Prostaglandin E<sub>2</sub>-Induced Relaxation of Preterm Ovine Pulmonary Arteries
Authors: Gao Yuansheng , Tolsa Jean-Francois , Shen Hai , Raj J.Usha 
Published: April 2003

β-Adrenergic agonists and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) play an important role in perinatal pulmonary circulation. We have determined the effect of antenatal glucocorticoid treatment on isoprenaline- and PGE<sub>2</sub>-mediated relaxation of pulmonary arteries of newborn preterm lambs. Ovine fetuses (121 days of gestation; term = 150 days) received a single intramuscular dose of betamethasone (0.5 mg/kg) or saline. Fifteen hours after the injection, the lambs were delivered, ventilated for 3 h, and sacrificed. The fourth-generation pulmonary arteries were dissected and cut into rings for study. In endothelin-1-preconstricted vessels, isoprenaline, PGE<sub>2</sub>, and forskolin (an activator of adenylyl cyclase) induced greater relaxations of pulmonary arteries of betamethasone-treated lambs than those of controls. 8-Bromo-cyclic adenosine monophosphate, a cell membrane permeable analogue of cyclic adenosine monophosphate, caused similar relaxation of all vessels. When stimulated with isoprenaline and PGE<sub>2</sub>, the adenylyl cyclase activity of crude membrane preparations of pulmonary arteries treated with betamethasone was greater than that of controls. These results show that single-dose antenatal betamethasone treatment enhances relaxation of pulmonary arteries of preterm lambs induced by isoprenaline and PGE<sub>2</sub> and that an enhanced adenylyl cyclase activity contributes to the effect of betamethasone on pulmonary arteries of preterm lambs.
Growth Hormone, Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3 Are Regulated Differently in Small-for-Gestational-Age and Appropriate-for-Gestational-Age Neonates
Authors: Cance-Rouzaud A. , Laborie S. , Bieth E. , Tricoire J. , Rolland M. , Grandjean H. , Rochiccioli P. , Tauber M. 
Published: April 2003

Growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were measured in 90 neonates during the first 5 days of life. Twenty-six small-for-gestational-age (SGA) neonates were compared with 64 appropriate-for-gestational-age (AGA) neonates. There were no differences in nutritional status between the 2 groups. Mean GH levels were significantly higher in the SGA group (53.4 ± 30.8 vs. 39.9 ± 23.3 µg/l; p < 0.05). In both groups GH levels correlated with birth weight (expressed as SDS) but not with gestational age. IGF-I levels were significantly lower in SGA neonates (6.6 ± 4.0 vs. 11.7 ± 8.2 ng/ml; p < 0.01). In SGA neonates with short stature, IGF-I levels were lower and GH levels were higher than in normal stature SGA neonates. IGFBP-3 levels were significantly lower in SGA neonates than in AGA neonates (0.72 ± 0.40 vs. 0.98 ± 0.43 µg/l; p < 0.01). IGF-I and IGFBP-3 correlated with gestational age in AGA but not in SGA neonates and there was no correlation with birth weight in either group. Our data provide evidence for a graduation in the severity of impact of fetal ‘malnutrition’ on the somatotropic axis and on intrauterine growth. The most severe state (SGA with short stature) was associated with a GH-resistance syndrome, characterized by very low IGF-I levels and high GH levels.