Renal excretion of sucrose after transfusion of sucrose containing red cell concentrates

The elimination of sucrose from plasma and the urinary excretion after transfusions of 394 units of sucrose containing red cell concentrates (RCC) to 108 patients has been studied. 70 mmol sucrose corresponding 3 units of RCC were eliminated from the blood plasma to 90% within 3 hours and excreted by kidneys to 55-80% within 12 hours. The rate of excretion depended on the kidney function. The transfusion of RCC resuspended with the sucrose-rich CSD-AG preservation solution (80 mmol sucrose/l RCC) raised the hemoglobin concentration in patient's blood by 0.5-0.6 mmol/l related to 1 unit of RCC.     

Effects of dietary paraffin, squalane and sucrose polyester on residue disposition and elimination of hexachlorobenzene in rats

Previous studies have shown addition of light liquid paraffin to enhance the elimination of organochlorine xenobiotics. In the present study the effect of paraffin on the elimination of [¹⁴C]hexachlorobenzene (HCB) was compared with the effect of possible alternative compounds, squalane and sucrose polyester (SPE). Four groups of 7 rats were fed a diet containing 1.5 ppm [¹⁴C]HCB for 4 days followed by 10 days on HCB-free diet. Thereafter one group (control) remained on this diet whereas the other 3 groups received a diet supplemented with 8% (w/w) paraffin, squalane or SPE, respectively. Radioactivity in urine and faeces was measured daily and at the end of the experiment in samples of abdominal fat, muscle, liver, kidney and blood. Dietary treatment with either paraffin, squalane or SPE markedly enhanced faecal excretion of [¹⁴C]HCB, whereas urinary excretion was not affected. Both the time course as well as the extent of faecal [¹⁴C]HCB elimination were similar in the treated groups. After 3 weeks of treatment the amount of [¹⁴C]HCB excreted with faeces was about three times higher in treated animals than in controls. The half-life (t_1/2) of [¹⁴C]HCB elimination from the body was markedly decreased in treated animals (mean 34–38 days) compared to controls (110 days). [¹⁴C]HCB concentrations in some major tissues were significantly reduced to the same extent by all three dietary regimens. Thus squalane and SPE are as effective as paraffin in removing HCB from contaminated animals.     

An isotopic study of oxalate excretion in sheep.

Intravenously injected 14C labelled oxalate was rapidly removed from the blood stream via the kidney in 2 sheep, 75% being cleared within 8 h. Mean daily urinary oxalate excretions over 5 days were 21-2 and 27-5 mg and the derived plasma oxalate concentrations were 52-6 and 74-4 mug/100 ml, respectively. Oxalate was both filtered and secreted by the renal tubule with oxalate/inulin ratios varying from 1-11 to 1-57 in 6 normal sheep. A large increase in calcium excretion induced by calcium borogluconate infusion over 5 days was accompanied by a small but consistent increase in urinary oxalate excretion relative to calcium. Oxalate in blood was to be found mainly in the plasma, there being a small (8%) proporation within erythrocytes. This is lower than that reported for man, and yet in its excretion of oxalate via the kidney the sheep appears to closely resemble man and dog.     

Kidney pathology precedes and predicts the pathological cascade of cerebrovascular lesions in stroke prone rats

Introduction

Human cerebral small vessel disease (CSVD) has been hypothesized to be an age-dependent disease accompanied by similar vascular changes in other organs. SHRSP feature numerous vascular risk factors and may be a valid model of some aspects of human CSVD. Here we compare renal histopathological changes with the brain pathology of spontaneously hypertensive stroke-prone rats (SHRSP).

Material and Methods

We histologically investigated the brains and kidneys of 61 SHRSP at different stages of age (12 to 44 weeks). The brain pathology (aggregated erythrocytes in capillaries and arterioles, microbleeds, microthromboses) and the kidney pathology (aggregated erythrocytes within peritubular capillaries, tubular protein cylinders, glomerulosclerosis) were quantified separately. The prediction of the brain pathology by the kidney pathology was assessed by creating ROC-curves integrating the degree of kidney pathology and age of SHRSP.

Results

Both, brain and kidney pathology, show an age-dependency and proceed in definite stages whereas an aggregation of erythrocytes in capillaries and arterioles, we parsimoniously interpreted as stases, represent the initial finding in both organs. Thus, early renal tubulointerstitial damage characterized by rather few intravasal erythrocyte aggregations and tubular protein cylinders predicts the initial step of SHRSPs'' cerebral vascular pathology marked by accumulated erythrocytes. The combined increase of intravasal erythrocyte aggregations and protein cylinders accompanied by glomerulosclerosis and thrombotic renal microangiopathy in kidneys of older SHRSP predicts the final stages of SHRSPs'' cerebrovascular lesions marked by microbleeds and thrombotic infarcts.

Conclusion

Our results illustrate a close association between structural brain and kidney pathology and support the concept of small vessel disease to be an age-dependent systemic pathology. Further, an improved joined nephrologic and neurologic diagnostic may help to identify patients with CSVD at an early stage.     

Urinary Concentration of Monocyte Chemoattractant Protein-1 in Idiopathic Glomerulonephritis: A Long-Term Follow-Up Study

Background

Monocyte chemoattractant protein-1 (MCP-1), which is up regulated in kidney diseases, is considered a marker of kidney inflammation. We examined the value of urine MCP-1 in predicting the outcome in idiopathic glomerulonephritis.

Methods

Between 1993 and 2004, 165 patients (68 females) diagnosed with idiopathic proteinuric glomerulopathy and with serum creatinine <150 µmol/L at diagnosis were selected for the study. Urine concentrations of MCP-1 were analyzed by ELISA in early morning spot urine samples collected on the day of the diagnostic kidney biopsy. The patients were followed until 2009. The progression rate to end-stage kidney disease was calculated using Kaplan–Meier survival analysis. End-stage kidney disease (ESKD) was defined as the start of kidney replacement therapy during the study follow-up time.

Results

Patients with proliferative glomerulonephritis had significantly higher urinary MCP-1 excretion levels than those with non-proliferative glomerulonephritis (p<0.001). The percentage of patients whose kidney function deteriorated significantly was 39.0% in the high MCP-1 excretion group and 29.9% in the low MCP-1 excretion group. However, after adjustment for confounding variables such as glomerular filtration rate (GFR) and proteinuria, there was no significant association between urine MCP-1 concentration and progression to ESKD, (HR = 1.75, 95% CI = 0.64–4.75, p = 0.27).

Conclusion

Our findings indicate that progression to end-stage kidney disease in patients with idiopathic glomerulopathies is not associated with urine MCP-1 concentrations at the time of diagnosis.     

Fermented soybean-derived Touchi-extract with anti-diabetic effect via alpha-glucosidase inhibitory action in a long-term administration study with KKAy mice.

A water-soluble Touchi-extract (TE) exerts a potent inhibitory activity against rat intestinal alpha-glucosidase in foodstuffs, and elicited anti-glycemic effects in rats and humans with single-bolus oral administration. In the present study, genetically modified diabetic model KKAy mice were used to examine the long-term effects of TE. Eight-week-old male KKAy mice were fed with CE-2 chow containing 0.08 and 0.4% of TE for 60 days. In the latter group, fasting blood glucose levels decreased (6.68 +/- 0.41 mmol/L) significantly (p<0.05) after a 60-day ingestion period compared with controls (8.75 +/- 0.54 mmol/L). Moreover, postprandial blood glucose levels were also significantly reduced (16.79 +/- 2.28 mmol/L; p<0.01) after ingesting TE for only 30 days compared with controls (28.49 +/- 0.59 mmol/L). On oral TE treatment for 60 days, postprandial increases in the blood glucose level after oral loading of sucrose (2 g/kg) at 30 (p<0.05) and 60 (p<0.01) min were significantly depressed compared with controls. Indexes for serum lipids; viz., total cholesterol (p<0.05) and triglyceride (p<0.01) levels significantly decreased after TE ingestion. Indexes for hepatic functions, such as glutamic-oxaloacetic transaminase (p<0.01), glutamic-pyruvic transaminase and gama-glutamyl transpeptide levels, were similarly suppressed. Organ weights of the heart, kidney, jejunum, liver and spleen increased in control KKAy mice due to hyperinsulinemia. Interestingly, the respective organ weights decreased (p<0.05, 0.01) and the jejunum length was reduced (p<0.05) significantly in the TE-treated groups. All in all, TE demonstrated an anti-hyperglycemic effect and may have potential use in the management of non-insulin-dependent diabetic mellitus.     

Safety profile of Coartem®: the evidence base

Background

Dihydroartemisinin (DHA), a powerful anti-malarial drug, has been used as monotherapy and artemisinin-based combination therapy (ACT) for more than decades. So far, however, the tissue distribution and metabolic profile of DHA data are not available from animal and humans.

Methods

Pharmacokinetics, tissue distribution, mass balance, and elimination of [¹⁴C] DHA have been studieded in rats following a single intravenous administration. Protein binding was performed with rat and human plasma. Drug concentrations were obtained up to 192 hr from measurements of total radioactivity and drug concentration to determine the contribution by the parent and metabolites to the total dose of drug injected from whole blood, plasma, urine and faecal samples.

Results

Drug was widely distributed after 1 hr and rapidly declined at 24 hr in all tissues except spleen until 96 hrs. Only 0.81% of the total radioactivity was detected in rat brain tissue. DHA revealed a high binding capacity with both rat and human plasma proteins (76–82%). The concentration of total radioactivity in the plasma fraction was less than 25% of that in blood total. Metabolism of DHA was observed with high excretion via bile into intestines and approximately 89–95% dose of all conjugations were accounted for in blood, urine and faeces. However, the majority of elimination of [¹⁴C] DHA was through urinary excretion (52% dose). The mean terminal half-lives of plasma and blood radioactivity (75.57–122.13 h) were significantly prolonged compared with that of unchanged DHA (1.03 h).

Conclusion

In rat brain, the total concentration of [¹⁴C] was 2-fold higher than that in plasma, indicating the radioactivity could easily penetrate the brain-blood barrier. Total radioactivity distributed in RBC was about three- to four-fold higher than that in plasma, suggesting that the powerful anti-malarial potency of DHA in the treatment of blood stage malaria may relate to the high RBC binding. Biliary excretion and multiple concentration peaks of DHA have been demonstrated with high urinary excretion due to a most likely drug re-absorption in the intestines (enterohepatic circulation). The long lasting metabolites of DHA (> 192 hr) in the rats may be also related to the enterohepatic circulation.     

Tissue distribution, elimination, and metabolism of [3H]leukotriene C4 by the conscious marine toad, Bufo marinus.

Tissue distribution, elimination, and metabolism of 3H-labelled leukotriene (LT) C4 were studied in ureter-catheterized conscious marine toads, Bufo marinus. Six and 24 h after injection, organs containing the highest percent of injected radioactivity were small intestine, liver, and kidney. Radioactivity declined in these organs at 24 h by approximately threefold. Peak elimination time for radioactivity in the urine was between 2 and 4 h after the injection. During the 24-h collection period, 55.2 +/- 0.2% of the injected radioactivity was eliminated in the urine. Polar metabolites represented 40.3 +/- 1.1, 57.3 +/- 5.6, and 62.8 +/- 1.6% of the radioactivity at 2, 4, and 6 h, respectively. The primary urinary polar metabolite was 20-carboxy-LTE4, with 18-carboxydinor-LTE4 and 20-hydroxy-LTE4 also present. [3H]LTE4 decreased from 37.2 +/- 1.8% at 2 h to 15.8 +/- 3.3 and 15.0 +/- 2.1% of the radioactivity at 4 and 6 h, respectively. Bile radioactivity was low. N-Acetyl-LTE4 was not detected in urine or bile samples. Radioactivity in the pan water was 14.3 +/- 2.4 and 15.8 +/- 2.5% of the injected radioactivity, at 6 and 24 h, respectively, suggesting that the skin was a route for excretion of leukotrienes. The marine toad is an interesting model demonstrating both similarities and differences from mammals in distribution, elimination, and metabolism of peptide leukotrienes.     

Pharmacokinetics of semisynthetic cephalosporins for parenteral use on surgical patients]

Pharmacokinetics of 4 cephalosporanic antibiotics for parenteral use, i. e. cephaloridine, cephradine, cephazoline and cephacetryl was studied in surgical patients with normal function of the kidneys and liver. The first 3 drugs were well absorbed after intramuscular administration, their maximum serum levels being achieved during the first hour. High blood levels of cephacetryl were determined after its intravenous administration. When cephaloridine, cephradine and cephazoline were administered in equal doses, it was found that the first 2 drugs did not practically differ with respect to the values of the serum levels, the rate of elimination from the blood, the rate and level of excretion with the urine. Cephazoline was characterized by higher blood levels and slower elimination from the blood.     

The purine nucleotide cycle in the regulation of ammoniagenesis during induction and cessation of chronic acidosis in the rat kidney.

The effect of chronic acid feeding and its subsequent withdrawal was determined on the amounts of the metabolic intermediates and enzymic activities of the purine nucleotide cycle. Sprague-Dawley rats were given 1.5% (w/v) NH4Cl in their drinking water for 5 days. The renal excretion of NH3 rose 70-fold and the rats developed acidosis. The amount of renal IMP rose from a control value of 4.5 +/- 2.2 to 20.4 +/- 3.7nmol/g of kidney after 48h of acid feeding (P less than 0.001) and fell to normal within 48h of the recovery. Adenylosuccinate concentrations fell from a control value of 4.5 +/- 0.9nmol/g of kidney to 1.2 +/- 0.3nmol/g (P less than 0.005) by day 5 of acidosis and continued to fall to undetectable values by 48h after recovery. The amount of AMP remained constant through the acid-feeding and the recovery periods. The activity of adenylosuccinate synthetase, the rate-limiting enzyme of the purine nucleotide cycle, paralleled the rise and fall in NH3 excretion. The activities of phosphate-dependent glutaminase and glutamate dehydrogenase were elevated during the acid-feeding and the recovery period. Thus changes in the purine nucleotide cycle correlate with changes in NH3 excretion to a more parallel degree than does the activity of glutaminase or glutamate dehydrogenase.     

The biological fate in rats of vinyl chloride in relation to its oncogenicity.

The main eliminative route for [14C]vinyl chloride after oral, i.v. or i.p. administration to rats is pulmonary; both unchanged vinyl chloride and vinyl chloride-related CO2 are excreted by that route and the other [14C] metabolites via the kidneys. After intragastric administration, pulmonary output of unchanged vinyl chloride is proportional to the logarithm of reciprocal dose. Excretion patterns after i.v. and i.p. injections are predictable from the characteristics of excretion following oral administration. Pulmonary excretion of unchanged vinyl chloride after oral dosing is complete within 3-4 h, but pulmonary elimination of CO2 and renal excretion of metabolites occupies 3 days. In comparison, 99% of a small i.v. dose is excreted unchanged within 1 h of injection; 80% within 2 min. The rate of elimination of a single oral doses of [14C]vinyl chloride is uninfluenced by up to 60 days' chronic dosing with the unlabelled substance. The distribution volume of vinyl chloride as displayed by whole-animal autoradiography agrees with deductions from excretion data. Small localization of 14C in the para-auricular region of appropriate sections occurs in sectioned tubules, belonging possibly to the Zymbal glands. Biotransformation of vinyl chloride into S-(2-chloroethyl) cysteine and N-acetyl-S-(2-chloroethyl) cysteine occurs through addition of cysteine, and biotransformation into: (i) chloroacetic acid, thiodiglycollic acid and glutamic acid, and (ii) into formaldehyde (methionine, serine), CO2 and urea is explicable in terms of an associative reaction with molecular O2 involving a singlet oxygen bonded transition state in dynamic equilibrium with a cyclic peroxide ground state. There is no evidence for chloroethylene oxide formation.Thiodiglycollic acid is the major metabolite of chloroacetic acid in rats; more than 60% of the dose. The interaction of vinyl chloride and of its primary metabolites with the intermediates of mammalian metabolism is discussed in relation to the oncogenicity of that substance.     

An In Vitro Model of Skeletal Muscle Volume Regulation

Introduction

Hypertonic media causes cells to shrink due to water loss through aquaporin channels. After acute shrinkage, cells either regulate their volume or, alternatively, undergo a number of metabolic changes which ultimately lead to cell death. In many cell types, hypertonic shrinkage is followed by apoptosis. Due to the complex 3D morphology of skeletal muscle and the difficulty in obtaining isolated human tissue, we have begun skeletal muscle volume regulation studies using the human skeletal muscle cell line TE671RD. In this study we investigated whether hypertonic challenge of the human skeletal muscle cell line TE671RD triggered cell death or evoked a cell volume recovery response.

Methods

The cellular volume of TE671RD cells was calculated from the 2D surface area. Cell death was assessed by both the trypan blue live/dead assay and the TUNEL assay.

Results

Medium osmolality was increased by addition of up to 200mM sucrose. Addition of 200mM sucrose resulted in mean cell shrinkage of 44±1% after 30mins. At later time points (2 and 4 hrs) two separate cell subpopulations with differing mean cell volume became apparent. The first subpopulation (15±2% of the total cell number) continued to shrink whereas the second subpopulation had an increased cell volume. Cell death was observed in a small proportion of cells (approximately 6-8%).

Conclusion

We have established that a substantial proportion of TE671RD cells respond to hypertonic challenge with RVI, but that these cells are resistant to hypertonicity triggered cell death.     

Asymmetrical dimethylarginine plasma clearance persists after acute total nephrectomy in rats

Elevated plasma concentrations of symmetrical dimethylarginine (SDMA) and asymmetrical dimethylarginine (ADMA) are repeatedly associated with kidney failure. Both ADMA and SDMA can be excreted in urine. We tested whether renal excretion is necessary for acute, short-term maintenance of plasma ADMA and SDMA. Sprague-Dawley rats underwent sham operation, bilateral nephrectomy (NPX), ureteral ligation, or ureteral section under isoflurane anesthesia. Tail-snip blood samples (250 microl) were taken before and at 6- or 12-h intervals for 72 h after operation. Plasma clearance was assessed in intact and NPX rats. High-performance liquid chromatography determined SDMA and ADMA concentrations. Sodium, potassium, creatinine, blood urea nitrogen (BUN), and body weight were also measured. Forty-eight hours after NPX, SDMA increased 25 times (0.23 +/- 0.03 to 5.68 +/- 0.30 microM), whereas ADMA decreased (1.17 +/- 0.08 to 0.73 +/- 0.08 microM) by 38%. Creatinine and BUN increased, paralleling SDMA. Sham-operated animals showed no significant changes. Increased SDMA confirms continuous systemic production of SDMA and its obligatory renal excretion, much like creatinine. In contrast, decreased plasma ADMA suggests that acute total NPX either reduced systemic ADMA formation and/or systemic hydrolysis of ADMA increased 48-h post-NPX. However, plasma clearance of ADMA appeared unchanged 48 h after NPX. We conclude that renal excretory function is needed for SDMA elimination but not needed for acute, short-term ADMA elimination in that systemic hydrolysis is fully capable of clearing plasma ADMA.     

Comparison of the elimination between perfluorinated fatty acids with different carbon chain length in rats

Elimination in urine and feces was compared between four perfluorinated fatty acids (PFCAs) with different carbon chain length. In male rats, perfluoroheptanoic acid (PFHA) was rapidly eliminated in urine with the proportion of 92% of the dose being eliminated within 120 h after an intraperitoneal injection. Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) was eliminated in urine with the proportions of 55, 2.0 and 0.2% of the dose, respectively. By contrast, four PFCAs were eliminated in feces with the proportion of less than 5% of the dose within 120 h after an injection. In female rats, the proportions of PFOA and PFNA eliminated in urine within 120 h were 80% and 51% of the dose, respectively, which were significantly higher compared with those in male rats. There was the tendency that PFCA with longer carbon chain length is less eliminated in urine in both male and female rats. Fecal elimination of PFCAs was not different between PFCAs in female rats and comparable to those in male rats. The rates of biliary excretion of PFCAs in male rats were slower than those in female rats. Sex-related difference in urinary elimination of PFOA was abolished when male rats had been castrated. On the contrary, treatment with testosterone suppressed the elimination of PFOA in urine in both castrated male rats and female rats. The effect of testosterone was in a time- and dose-dependent manner. These results suggest that PFCAs are distinguished by their carbon chain length by a renal excretion system, which is regulated by testosterone.     

The metabolism of selenomethionine, Se-methylselenocysteine, their selenonium derivatives, and trimethylselenonium in the rat

The formation of dimethylselenide (respiratory) and trimethylselenonium (urinary) metabolites from [75Se]selenomethionine, [75Se]methylselenomethionineselenonium, [75Se]methylselenocysteine, [75Se]dimethylselenocysteineselenonium, and [75Se]trimethylselenonium was determined using single sc doses of 2 or 0.064 mg Se/kg in male and female rats. The 75Se content of liver, kidney, pancreas, testis, spleen, blood, heart, brain, and skeletal muscle was determined at 0.5 and 24 h. Respiratory 75Se after 24 h was greatest from Se-dimethylselenocysteineselenonium (38 and 17% for the high and low doses, respectively). Respiratory 75Se was about 8% for the high dose of Se-methylselenocysteine and was less for all other compounds. Total 75Se excretion in the urine was highest from rats given trimethylselenonium (about 90%, both doses) and was lowest from rats given selenomethionine (4%, low dose). Urine samples were chromatographed on SP-Sephadex cation-exchange columns and 75Se was eluted with ammonium formate; trimethylselenonium was precipitated with ammonium Reineckete solution and trimethylsulfonium carrier. Urinary trimethylselenonium excretion was greatest from rats given trimethylselenonium, but rats given Se-dimethylselenocysteineselenonium (low dose) excreted 35-45% of the dose as trimethylselenonium ion. The lowest quantity of trimethylselenonium was excreted by rats given the low dose of selenomethionine (0-3%). Pancreas, kidney, and liver showed the highest uptake (% of dose/g) of the selenium compounds. Trimethylselenonium was highly concentrated by the kidney and also showed high myocardial uptake (heart/blood ratio = 5) 0.5 h after injection; the selective uptake of trimethylselenonium in heart was not observed for the other selenonium compounds.     

The absorption, metabolism and excretion of dimethyl sulfoxide by rhesus monkeys

The absorption and excretion of dimethyl sulfoxide (DMSO) were studied in Rhesus monkeys (Macaca mulatta) given daily oral doses of 3 gms DMSO/kg B.W. for 14 days. DMSO and its major metabolite, dimethyl sulfone (DMSO2), were measured in serum, urine and feces by gas-liquid chromatography. DMSO was absorbed rapidly, reached a steady state blood level after 1 day and then was cleared from blood within 72 hrs after ending treatment. Serum DMSO declined in a linear fashion on semilogarithmic coordinates as described by second order kinetics. It had a half-life of 16 hrs. DMSO2 appeared in blood within 2 hrs and reached a steady state concentration after 4 days of treatment. DMSO2 was cleared from blood about 120 hrs after DMSO administration was stopped. Its half-life in blood was calculated to be 38 hrs. Urinary excretion of unmetabolized DMSO and DMSO2 accounted for about 60% and 16%, respectively, of the total ingested dose. Neither DMSO nor DMSO2 was detected in fecal samples. However, when added to fecal samples, DMSO was degraded rapidly. Although dimethyl sulfide (DMS) was not measured, some DMSO was metabolized to this compound because of the particular sweetness of breath of the monkeys. We conclude that the absorption of DMSO by monkeys is similar to that for humans, but that its conversion to DMSO2 and urinary elimination are more rapid in monkeys.     

Plasma thyroxine and cortisol profiles and gill and kidney Na+/K+-ATPase and SDH activities during acclimation of the catfish Heteropneustes fossilis (bloch) to higher salinity, with special reference to the effects of exogenous cortisol on hypo-osmoregulatory ability of the catfish

When the stenohaline catfish Heteropneustes fossilis was transferred from fresh water (FW) to 30% seawater (SW), the Na(+)/K(+)-ATPase activity significantly increased in the kidney, while in gills it remained more or less constant. A reverse pattern was observed for succinic dehydrogenase (SDH) activity inasmuch as it significantly increased in gills and remained unchanged in the kidney. Plasma osmolality significantly increased within 3 days of transfer to 30% SW and remained significantly higher throughout the duration of experiment. These results suggest that catfish gills may not be able to reverse their function from salt uptake in FW to salt excretion at higher salinity, and that the elimination of monovalent as well as divalent ions is performed by the kidney but not the gills. The significant decline in plasma cortisol (F) levels following transfer to higher salinity may not be due to reduced production but rather to an enhanced utilization and clearance rate, a conclusion supported by the fact that exogenous administration of cortisol acetate (FA) resulted in significant increases in branchial and renal Na(+)/K(+)-ATPase in FW and 30% SW. FA also improved the plasma osmotic regulatory ability of the catfish, possibly due to a change in branchial function from salt-absorption to salt excretion, as was evident from a significant increase in branchial Na(+)/K(+)-ATPase activity in the fish in 30% SW pretreated with FA for 5 days. Consistently higher levels of plasma thyroxine (T4) following transfer to higher salinity suggest the involvement of this hormone at higher salinity.     

Correlation of dose-antimicrobial effect in modeling in vitro pharmacokinetic profiles of normal and impaired elimination of antibiotics

Relationships between concentration and antimicrobial effect (AME) of sisomicin (SMN) and cefotaxime (CTX) were established by simulating their pharmacokinetic profiles in an in vitro dynamic model. The AME duration (TE, time shift between the curves of bacteria heat output in the presence and absence of the antibiotics) or intensity (IE, area between the above curves) for both the antibiotics depended in the same way on the area under the concentration/time curve (AUC, mimicing of intravenous administration of the antibiotics in various doses). At low and moderate values of the AUC the dependences of IE or TE vs the AUC (the bacteriostatic phase of the AME development) were of the sigmoid shape while at high values of the AUC there was a marked increase in IE or TE (the bactericidal phase). The patterns of the IE or TE vs AUC curves in impaired antibiotic elimination were analogous. At the same time the IE or TE vs AUC curves for both the antibiotics under simulation of normal elimination (T 1/2, SMN-2.1 h, T 1/2, CTX-1.2 h) and impaired one (T 1/2, SMN-8.3 h, T 1/2, CTX-4.6 h) did not match. In the first case the AMESMN was on the whole higher and the AMECTX was lower than in the second case. Therefore, in patients with renal failure the efficient concentration of the aminoglycoside in blood can be higher and that of the cephalosporin on the contrary can be lower than the normal.     

Evaluation of Transient Elastography,Acoustic Radiation Force Impulse Imaging (ARFI), and Enhanced Liver Function (ELF) Score for Detection of Fibrosis in Morbidly Obese Patients

Background

Liver fibrosis induced by non-alcoholic fatty liver disease causes peri-interventional complications in morbidly obese patients. We determined the performance of transient elastography (TE), acoustic radiation force impulse (ARFI) imaging, and enhanced liver fibrosis (ELF) score for fibrosis detection in bariatric patients.

Patients and Methods

41 patients (median BMI 47 kg/m²) underwent 14-day low-energy diets to improve conditions prior to bariatric surgery (day 0). TE (M and XL probe), ARFI, and ELF score were performed on days -15 and -1 and compared with intraoperative liver biopsies (NAS staging).

Results

Valid TE and ARFI results at day -15 and -1 were obtained in 49%/88% and 51%/90% of cases, respectively. High skin-to-liver-capsule distances correlated with invalid TE measurements. Fibrosis of liver biopsies was staged as F1 and F3 in n = 40 and n = 1 individuals. However, variations (median/range at d-15/-1) of TE (4.6/2.6–75 and 6.7/2.9–21.3 kPa) and ARFI (2.1/0.7–3.7 and 2.0/0.7–3.8 m/s) were high and associated with overestimation of fibrosis. The ELF score correctly classified 87.5% of patients.

Conclusion

In bariatric patients, performance of TE and ARFI was poor and did not improve after weight loss. The ELF score correctly classified the majority of cases and should be further evaluated.     

Effect of diuretics on the distribution and renal excretion of lithium in rats of different ages

The postnatal development of the renal lithium elimination is maturated earlier than that of renal sodium excretion. The filtered lithium is reabsorbed to a great amount in the kidney (70-80%). 90% of the administered lithium is eliminated by the kidney. Acetazolamide stimulates the renal lithium excretion in young and adult rats. Other diuretics with different sites of attack are not able to influence the elimination of lithium. Also, a forced diuresis does not change the elimination rate of lithium. The well-known interactions between sodium and ithium must have their cause in extrarenal processes.