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Ichthyotoxic ARF after fish gallbladder ingestion: a large case series from Vietnam.

Fish gallbladders are consumed in rural areas of Asia as a traditional medicine to improve symptoms of arthritis, decreased visual acuity, and impotence. Consumption of large amounts of this traditional medicine can result in systemic toxicities; in particular, acute renal failure. We reviewed records of all admissions to Cho Ray Hospital (Ho Chi Minh City, Vietnam) between January 1995 and December 2000 after this ingestion. Clinical courses and outcomes were similar in 16 of 17 patients. Within hours, patients experienced profuse vomiting (n = 16) and diarrhea (n = 15). All developed acute renal failure, with a mean serum creatinine concentration of 14.7 +/- 3.9 mg/dL (1,299.5 +/- 344.8 micromol/L). Four patients administered intravenous fluid (IVF) developed extracellular fluid volume overload, as did 1 patient not administered IVF. Time to peak creatinine concentration was 8.6 +/- 3.0 days, which was accompanied by decreased urine volume (174.7 +/- 161.6 mL/24 h). Blood pressure remained normal, with a mean arterial pressure of 91 +/- 12 mm Hg. Twelve patients required renal replacement therapy. A mean of 1.9 +/- 1.1 hemodialysis sessions was performed per patient. Sixteen patients recovered renal function; 1 patient died of fulminant hepatic failure. Kidney biopsies showed features of acute tubular injury. Acute renal failure after fish gallbladder ingestion is characterized by a failure to respond to IVF, an 8.6-day interval to peak creatinine level, frequent need for dialysis therapy, and findings on renal biopsy consistent with acute tubular necrosis. Acute renal failure after fish gallbladder ingestion has an excellent prognosis. However, death from fulminant hepatic failure can occur.

Acute Kidney Injury↗

Plasma extracellular-superoxide dismutase in the acute phase response induced by surgical trauma and inflammatory disorders.

Trauma, inflammatory disorders and other perturbations induce the so-called acute phase response in organisms. The phenomenon encompasses many physiological alterations including typical changes in plasma proteins. Often an accumulation and activation of superoxide radical-producing leucocytes occurs at the site of perturbation. The major enzymic protector against superoxide radicals in plasma and other extracellular fluids is extracellular-superoxide dismutase. The acute phase response of extracellular-superoxide dismutase was investigated in two groups, one comprising 13 patients in the postoperative period after surgical trauma and the other 15 patients with various inflammatory disorders. No significant positive or negative acute phase response of plasma extracellular-superoxide dismutase was revealed.

Acute-Phase Proteins↗

Rate of potassium exchange of the human erythrocyte.

1. The exchange of potassium by the human erythrocyte has been studied in vitro using radioactive potassium. 2. An incubation technique which maintains erythrocytes in an essentially normal state for over 48 hours was employed. 3. Exchange of radioactive potassium between the red cells and the extracellular fluid was regular and progressive, the specific activities of the intra- and extracellular fluids reaching equal values. This indicates that all the erythrocyte potassium is exchangeable and is exchanging at the same rate. 4. From these data, it was calculated that at 37 degrees C., 1.6 per cent of the erythrocyte potassium exchanges per hour, corresponding to an exchange of 1.5 mM of potassium per liter of red cells per hour. The time required for the exchange of 50 per cent of the red cell potassium is calculated to be 43 hours. 5. The temperature coefficient (Q(10)) of the potassium exchange rate is 2.2. This is the same as the temperature coefficient of the rate of utilization of glucose by the human erythrocyte. 6. Varying the percentage of red cells, plasma potassium concentration, initial glucose level, and pH between 7.0 and 7.7 had no effect on the potassium exchange rate.

Erythrocytes↗

Phenylethylamine-induced generation of reactive oxygen species and ascorbate free radicals in tobacco suspension culture: mechanism for oxidative burst mediating Ca2+ influx.

In the previous paper [Kawano et al. (2000a) Plant Cell Physiol. 41: 1251], we demonstrated that addition of phenylethylamine (PEA) and benzylamine can induce an immediate and transient burst of active oxygen species (AOS) in tobacco suspension culture. Detected AOS include H2O2, superoxide anion and hydroxyl radicals. Use of several inhibitors suggested the presence of monoamine oxidase-like H2O2-generating activity in the cellular soluble fraction. It was also suggested that peroxidase(s) or copper amine oxidase(s) are involved in the extracellular superoxide production as a consequence of H2O2 production. Since more than 85% of the PEA-dependent AOS generating activity was localized in the extracellular space (extracellular fluid + cell wall), extracellularly secreted enzymes, probably peroxidases, may largely contribute to the oxidative burst induced by PEA. The PEA-induced AOS generation was also observed in the horseradish peroxidase (HRP) reaction mixture, supporting the hypothesis that peroxidases catalyze the oxidation of PEA leading to AOS generation. In addition to AOS production, we observed that PEA induced an increase in monodehydroascorbate radicals (MDA) in the cell suspension culture and in HRP reaction mixture using electron spin resonance spectroscopy and the newly invented MDA reductase-coupled method. Here we report that MDA production is an indicator of peroxidase-mediated generation of PEA radical species in tobacco suspension culture.

Amines↗

Colloid solution therapy of experimental ischemic intestinal shock in rats.

This study evaluated the effects of varying colloid concentrations and infusion volumes on survival and plasma volume expansion in rats subjected to an intestinal ischemic shock. Up to 10% solutions of albumin and dextran-40 in lactated Ringer's solution, infused over a 6-h period, had the same effects on hematocrit (Hct) changes and survival patterns. Mean Hct values (45% to 50%) were independent of colloid solution concentration. With lactated Ringer's solution alone, Hct was 55%, despite the very large volume used; and less than 3% of the infused lactated Ringer's solution remained as plasma volume at 3 and 6 h of infusion. With increasing colloid concentration a greater proportion of the infused volume contributed to plasma volume. Of a 10% colloid solution, 50% and 34% remained as plasma volume at 3 and 6 h. For colloid concentrations between 1% and 3%, there was an equal distribution of infused fluid between the extracellular fluid space and the plasma. Survival rate, as measured by blood volume expansion, was greater with colloid solution concentrations between 2% and 4%.

Albumins↗

Neotrofin is transported out of brain by a saturable mechanism: possible involvement of multidrug resistance and monocarboxylic acid transporters.

Neotrofin (AIT-082; leteprinim potassium) is transported out of brain by a saturable mechanism and in this study the mechanisms mediating this efflux were evaluated. Intracerebroventricular coadministration of [(14)C]Neotrofin with verapamil, a P-glycoprotein inhibitor, probenecid, an organic anion transporter inhibitor, 3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571), a multidrug resistance-associated protein inhibitor, and salicylate or benzoate, both monocarboxylic acid transporter substrates, inhibited the efflux of [(14)C]Neotrofin. Additionally, Neotrofin inhibited the efflux of [(3)H]quinidine from brain. Compounds can diffuse from cerebrospinal fluid (CSF) into extracellular fluid of brain parenchyma and thus, efflux of [(14)C]Neotrofin after intracerebroventricular administration may indicate active transport across choroid plexus epithelium, brain capillary endothelium, or both. To determine whether [(14)C]Neotrofin efflux occurs at the brain capillary endothelium, experiments were performed in which [(14)C]Neotrofin was administered intraparenchymally. The t(1/2) for [(14)C]Neotrofin disappearance from brain after intraparenchymal administration was significantly lower than that for [(3)H]sucrose and the efflux of Neotrofin was inhibited by 600-fold excess of unlabeled Neotrofin, verapamil, MK571, and salicylate. Together, these data suggest that a saturable mechanism for the efflux of Neotrofin is located at the blood-brain barrier and possibly the blood-CSF barrier. It is likely that multiple transporters are involved in the efflux of Neotrofin and these may include multidrug resistance and monocarboxylic acid transporters. These data are discussed in detail with respect to the site of transporter expression, the recent identification of numerous multidrug resistance-associated protein and monocarboxylic acid transporter homologs, the existence of other potential brain efflux transporters, and the availability of specific pharmacological agents with which to distinguish these transporters.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Iatrogenic acute hyponatraemia in a college athlete.

Hyponatraemia is one of the most common electrolyte abnormalities, leading to significant morbidity and mortality. In the most basic sense, hyponatraemia can be due to sodium loss or fluid excess. The extracellular fluid status is used to clinically divide hyponatraemia into three categories to help to determine both the cause and treatment required. Hyponatraemic patients can be categorised on the basis of their fluid status as hypovolaemic, euvolaemic, or hypervolaemic. Another distinction to make in evaluating hyponatraemia is whether the onset was acute or chronic in nature. The case presented here is iatrogenic acute hypervolaemic hyponatraemia in a college athlete. The patient presented in respiratory distress with an altered mental status after the administration of hypotonic fluids for treatment of muscle cramps. Treatment included intubation, water restriction, and furosemide, to which he responded favourably. Hyponatraemia should be in the differential diagnosis for patients presenting after intravenous fluid administration.

Acute Disease↗

Quantitative confocal imaging along the crypt-to-surface axis of colonic crypts.

Quantitative confocal microscopy methods are used to measure events along the crypt-to-surface axis in living mouse colonic mucosa. Experiments visualize carboxyseminaphthorhodofluor-1 (SNARF-1; a pH-sensitive fluorescent dye) in the extracellular fluid to measure extracellular pH within an intact epithelium. Lucifer yellow (LY; a pH-insensitive dye) is used to control for fidelity of the optical path. Light scatter from colonic tissue caused SNARF-1 or LY fluorescence to decrease 3% per micrometer focal distance into tissue at both 640- and 580-nm emission wavelengths. However, dual emission ratios of LY fluorescence were constant as a function of focal distance into tissue or in the presence of short-chain fatty acids (SCFA). SCFA, known to cause changes in extracellular pH, cause maximal changes in crypt luminal pH at 10 microns from the crypt base. Maximal changes of pH in lamina propria occur higher along the crypt-to-surface axis than maximal changes in luminal pH. Lateral intercellular spaces between colonocytes are a separate microdomain in which pH is constant in absence vs. presence of SCFA and along the base-to-apex axis of colonocytes.

Animals↗

cAMP and calcium in generation of slow waves in cat colon.

Rhythmic oscillations in interactions between cAMP and calcium have been proposed to account for a variety of rhythmic phenomena in cells. This idea was investigated in relation to the rhythmic signals (electrical slow waves) found in the electromyogram of the cat colon. A longitudinal strip of muscularis propria from cat colon was studied in a superfusion bath that allowed recording of the electromyogram from eight sites that were 2 cm apart. The effect of increasing cAMP (by exposure of the tissue to cAMP, dibutyryl cAMP, isobutylmethylxanthine, theophylline, caffeine, and papaverine) was to reduce frequency and amplitude of slow waves and duration of migrating spike bursts. All these maneuvers raised tissue cAMP levels. Dibutyryl cGMP and cGMP had no effect. THe changes in slow waves, but not migrating spike bursts, seen with raised cAMP levels were partly reversed by raising the calcium concentration in the extracellular fluid. Raising the extracellular sodium and potassium concentrations had no effect. The results are consistent with the hypothesis that interactions between cAMP and calcium are involved in slow-wave generation in colon muscle.

1-Methyl-3-isobutylxanthine↗

Lumbar myelography with metrizamide in rabbits. An investigation of contrast media penetration and resorption.

Neurotoxicity from subarachnoid contrast media is probably related to their specific pharmacologic effects and to their penetration into the central nervous system. The lack of a barrier between the cerebrospinal fluid and the extracellular fluid of the brain and cord allows water-soluble contrast media to diffuse into the neural tissue. The aim of this investigation was to develop a method that allows one to quantify the neural tissue penetration for a given contrast medium in relation to the cerebrospinal fluid concentration and contact time and apply this to the use of metrizamide. The result shows a good correlation between iodine concentration in the lumbar cerebrospinal fluid and that in the lumbar cord suggestive of a simple diffusion. When time of sacrifice (contact time) is added as a covariant there is also some indication of retention of metrizamide in the neural tissue. The investigation also demonstrates that the resorption of the contrast medium in the rabbit in this experimental model is mainly in the lumbo-sacral region.

Animals↗

Refractory hypertension after renal transplantation.

Hypertension is a common problem encountered after renal transplantation. Many different mechanisms may be responsible for hypertension in this setting, and therapy will depend upon the mechanism(s) affecting the individual patient. Factors that may cause or aggravate post-transplantation hypertension include renal dysfunction secondary to rejection or other diseases of the transplanted kidney, renin production from the diseased native kidneys if these kidneys have not been surgically removed, extracellular fluid volume expansion, toxic effects of medications used after transplantation, especially cyclosporine and intravenous prednisolone, or primary hypertension in the donor or recipient. Renal artery stenosis may predispose to acute renal failure in the presence of treatment with angiotensin-converting enzyme inhibitors. Severe renal artery stenosis may also lead to refractory salt and water retention and fluid overload with congestive heart failure and hypertension, mediated primarily due to extracellular fluid volume excess. Therapy with percutaneous transluminal renal angioplasty or, as a last resort, surgery, can be successful in controlling these problems.

Adult↗

[Serial changes in body composition in patients with chronic renal failure on peritoneal dialysis].

Nutritional status is one of the most important factors affecting mortality and morbidity in chronic dialysis patients. There are, however, few data on serial body composition changes in these patients. To investigate serial changes in body composition in patients on peritoneal dialysis, we measured intracellular fluid volume(ICF), extracellular fluid volume(ECF), body protein volume(BPV), body fat volume(BFV) and bone mineral content(BMC) using multifrequency bioelectrical impedance analysis (MF-BIA). MF-BIA was performed in 35 patients, consisting of 21 men and 14 women with a mean age of 51.3 +/- 10.9 years, before and after one year of observation. At the baseline in male patients, ICF was 37.0 +/- 3.4%, ECF 19.7 +/- 1.6%, BPV 20.7 +/- 1.7%, BFV 18.1 +/- 6.6% and BMC 4.5 +/- 0.4% of body weight, and in female patients ICF was 34.4 +/- 2.6%, ECF 17.8 +/- 1.9% BPV 19.0 +/- 1.6%, BFV 24.4 +/- 6.2% and BMC 4.5 +/- 0.4% of body weight. In the group of patients whose body weight increased more than 3 kilograms(n = 9), the increase rate of BFV was 32.3 +/- 20.2%, significantly higher than that of the other segments(p < 0.001). On the other hand, in the group of patients whose body weight decreased more than 3 kilograms(n = 5), each segment showed the same extent of decrease and there was no significant difference in the decrease rates among each segment. In the group of patients whose body weight was stable(n = 21), changes in each body composition segment were extremely small. It could be concluded that the body weight increase is due mainly to increase in BFV and body weight decrease results from a concurrent decrease in each body composition segment in peritoneal dialysis patients.

Adult↗

The Sun Ancon Chi Machine Aerobic Exerciser: a new patient focused, home based therapy for people with chronic secondary leg lymphedema.

A significant proportion of those who survive lower torso cancer treatments will go on to develop clinically discernible bilateral or unilateral leg lymphedema. Although beneficial treatments exist for this condition, many are expensive and involve visits to outpatient clinics or allied health professionals--making the patient dependent upon others for treatment and maintenance. This clinical trial tested the efficacy of the Sun Ancon Chi Machine Aerobic Exerciser, a home based therapy that delivered both elevation and passive exercise to the legs. This machine was used in the participant's home according to a set regime with measurements being taken immediately before trial commencement, at weekly intervals and then 1 month after treatment cessation. After a three week treatment period there were statistically significant reductions in total leg volume and fluids, whole body extracellular fluid, weight and subjective leg symptoms. Lymphscintigraphy in a sub-group of patients suggested an increase in lymphatic transport in some individuals. Although some of the fluid and symptoms had returned at the 1 month follow up, none of the parameters had returned to pre-treatment levels. This finding indicates that this equipment may have ongoing beneficial effects. This clinical trial demonstrates that the Sun Ancon Chi Machine Aerobic Exerciser is an effective adjunct therapy that can be used in the patient's own home.

Chronic Disease↗

PET-based radiation dosimetry in man of 18F-fluorodihydrotestosterone, a new radiotracer for imaging prostate cancer.

UNLABELLED: 16 beta-fluoro-5 alpha-dihydrotestosterone (FDHT) is a promising new PET radiopharmaceutical for the imaging of prostate cancer. A recent clinical trial provided the opportunity for refinement of normal-tissue radiation-absorbed dose estimates based on quantitative PET. The objective of the current study was to derive estimates of normal-tissue absorbed doses for (18)F-FDHT administered to patients with advanced prostate cancer. METHODS: Absorbed dose estimates were derived from 10 (18)F-FDHT PET studies (administered activity, 111-407 MBq) of 7 prostate cancer patients. Activity concentrations in plasma and red marrow (assuming a plasmacrit of 0.58, an extracellular fluid fraction of 0.40, and equilibration of activity between plasma and marrow extracellular fluid) were measured ex vivo from a peripheral blood sample. Liver, spleen, urinary bladder contents, and total-body activities were measured by region-of-interest analysis of quantitative whole-body studies acquired with a dedicated PET scanner. Total organ activities and residence times were calculated from the respective PET scan-derived activity concentrations assuming standard (70 kg) man organ masses. Urinary excretion was corrected for hepatobiliary excretion (liver activity), and a first-order adjustment was made for the bladder-wall mass based on the patient's total-body mass. Mean organ absorbed doses were calculated with the MIRD formalism and the standard man model using the MIRDOSE3 software program. RESULTS: The absorbed doses (mean +/- SD) ranged from 0.00057 +/- 0.000281 cGy/MBq (to skin) to 0.00868 +/- 0.00481 cGy/MBq (to bladder wall) (voiding intervals, 1-2 h), and the effective dose equivalent was 0.00177 +/- 0.000152 cSv/MBq. CONCLUSION: The maximum absorbed dose among all tissues in all 10 studies, 0.0151 cGy/MBq, occurred for the urinary bladder wall (with hydration and 1- to 2-h voiding intervals). To ensure that the maximum normal-tissue absorbed dose is kept below the recommended maximum permissible dose of 5 cGy per single administration, a maximum administered activity of 331 MBq (5 cGy/[0.0151 cGy/MBq]) is recommended for (18)F-FDHT.

Body Burden↗

A pharmacological explanation of the use-dependency of the verapamil (and D-600) block of slow calcium channels.

Contractures of the toe muscles of frogs produced by 123 mM K+ were reduced or blocked by verapamil (or D-600) when applied in concentrations of 10(-7) M or more. In concentrations between 10(-7) and 3 X 10(-5) M or less, little or no reduction was produced in the first test with high K+ after drug application. When tests were repeated at 10- to 15-min intervals, block was produced. This block decreased and eventually disappeared if the muscles were kept in the drug solution without testing for 25 min or more. In contrast, at 10(-4) M verapamil, the first contracture in response to high K+ was reduced or blocked. If exposure to 10(-4) M verapamil was limited to 0.5 hr, then recovery occurred in drug-free solution, but if the muscles were exposed to this concentration of verapamil for 2.5 hr or longer, the K+ contracture remained blocked, even in drug-free solution. These results provided an explanation for the frequency- and use-dependency effects of verapamil and D-600. Briefly, this explanation is that the drug receptor is inside the calcium channel which is closed to the extracellular fluid in the resting or in the inactivated state but open to the intracellular fluid at all times. The drug receptors will be effectively occupied and a block produced when lower drug concentrations are used if the calcium channels are opened, but verapamil will leave its receptor and diffuse into the intracellular fluid when the extracellular channel openings are closed. Further details of this mechanism are given in the paper.

Animals↗

Severe lithium toxicity treated by hemodialysis: a case report.

A 51-year-old manic woman who developed acute severe lithium intoxication with neurotoxicity and nephrotoxicity during rapid abatement of manic episode was reported. The underlying causes of the serious toxicity were reviewed. Awareness and early detection of the toxic symptoms are emphasized in order to avoid permanent toxic sequelae. It is suggested that hemodialysis is the treatment of choice and should not be delayed, especially in severe toxic states and a daily 10 hours hemodialysis is needed to prevent the rebound effect as lithium in intracellular fluid equilibrates with extracellular fluid.

Humans↗

[Disturbances of Free Water and Electrolyte Metabolism: Three large groups are differentiated].

1. Disturbances of free water which are related to the whole body water and are always coupled with changes in the osmolality of the internal environment and also of the interior of the cells. 2. Isotonic changes of the volume of the extracellular fluid- edema or extracellular dehydration. The latter is always coupled with a hypovolemia and with a danger to the circulation which may end in shock. There is also a cumulative loss of potassium as a result of the dehydration reaction. 3. Disturbances of the intracellular water metabolism which are associated with disturbances of the potassium metabolism. These may have consequences for the function of striated and smooth muscles, for the function of the nerves and various enzyme systems.

Adult↗

Cerebrovascular smooth muscle cells internalize Alzheimer amyloid beta protein via a lipoprotein pathway: implications for cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is caused by the cerebrovascular deposition of Alzheimer amyloid beta protein (Abeta) and shows an increased incidence in carriers of the apolipoprotein E (APOE) epsilon4 genotype. To study the pathogenesis of CAA, primary cultures of human and canine smooth muscle cells from leptomeningeal vessels were incubated with fluorescein- and biotin-conjugated amyloid beta-protein. In the presence of human serum or cerebrospinal fluid, A beta1-40 and Abeta1-42 were rapidly internalized and appeared within endosomal and lysosomal vesicles. The accumulation of intracellular Abeta was enhanced by chloroquine and blocked by cycloheximide and brefeldin A and pretreatment with trypsin, suggesting that the internalization of Abeta occurs by receptor-mediated endocytosis. The internalization of Abeta was also inhibited by lipoprotein-deficient serum or by incubation with the 39-kd receptor-associated protein, indicating that Abeta is internalized via a receptor of the low-density lipoprotein receptor family. A lipoprotein pathway was confirmed by colocalization of cell surface-bound or internalized Abeta with APOE and low-density lipoprotein receptor-related protein. We propose a pathogenetic model of CAA, in which Abeta-APOE-complexes contained within the cerebrospinal fluid or the extracellular fluid of the brain are internalized and accumulated in cerebrovascular smooth muscle cells. Such a model could explain the preferential localization of CAA to the outer and middle layers of cortical and leptomeningeal arterioles, while indicating a mechanism by which the APOE genotype might determine the risk of CAA.

Amino Acid Sequence↗