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At least 865 records · Page 48Linked to original sources
PubMed2004

Highly potent 1-aminocyclohexane-1-carboxylic acid substituted V2 agonists of arginine vasopressin.

The synthesis and some pharmacological properties of two sets of analogues, one consisting of six peptides with 1-aminocyclohexane-1-carboxylic acid (Acc) in position 2 and the other with the amino acid in position 3, have been described. All the peptides were tested for their pressor, antidiuretic, and uterotonic in vitro activities. The Acc(2) modification has been shown to selectively modulate the activities of the analogues. Four of the compounds were highly potent antidiuretic agonists with different pressor and uterotonic activities. On the other hand, the 3-substituted counterparts failed to exhibit any of the activities. One exception was provided by the [Mpa(1),Acc(3),Val(4),D-Arg(8)]VP analogue, which exhibited antidiuretic activity matching that of AVP, yet, unlike AVP, it was fairly selective.

Amino Acids, Cyclic↗
PubMed1980

Indomethacin and the response to bumetanide.

Pretreatment of 8 normal subjects with 100 mg indomethacin decreased the response to bumetanide; cumulative 4-hr excretion of sodium due to 1.0 mg of bumetanide was reduced from 276 +/- 22.9 to 202 +/- 20.9 mEq (p less than 0.003). Effects on volume and Cl paralleled those on Na while K excretion was not affected. When response was analyzed as increment in fractional excretion over basal solute excretion determined from separate control studies, indomethacin decreased response, an effect differing from that of indomethacin on the response to furosemide. The importance and mechanism of the difference in the effect of indomethacin on bumetanide and furosemide is not known.

Adult↗
PubMed1987

Sulindac inhibits bumetanide-induced sodium and water excretion.

In an open-label pilot study, we investigated the effect of sulindac on bumetanide-induced diuresis. Nine healthy volunteers were placed on diets with a standard sodium and potassium content. Each volunteer received 1 mg bumetanide orally, and blood and urine samples were collected during an 8-hour period. Urinary losses were replaced isovolumetrically with intravenous normal saline solution. Creatinine clearance and sodium and potassium excretion were compared with and without sulindac pretreatment (200 mg administered orally b.i.d. for 5 days). Sulindac pretreatment resulted in a 22% decrease in the mean cumulative sodium excretion after 3 hours (p less than 0.05) and a 21% decrease in the mean urine flow rate after 2 hours (p less than 0.05). The results suggest that sulindac has an effect on the kidney similar to that of other nonsteroidal agents.

Adolescent↗
PubMed1997

Renal alpha 2a/d-adrenoceptor subtype function: Wistar as compared to spontaneously hypertensive rats.

1. The alpha 2a/d-adrenoceptor subtype in the rat kidney modulates solute excretion (osmolar clearance). Since the kidney plays a role in chronic regulation of blood pressure, altered renal function may be implicated in the development of hypertension. A second alteration-that of the alpha 2a/d-adrenoceptor subtype gene-has also been correlated with hypertension in rats and man. 2. We hypothesized that as a consequence of the altered alpha 2a/d-adrenoceptor subtype gene previously shown in spontaneously hypertensive (SH) rats, the increase in osmolar clearance following stimulation of the renal alpha 2a/d-subtype would be attenuated in SH rats as compared to normotensive Wistar rats. In contrast, based on the theory that such functional unresponsiveness of the alpha 2a/d-subtype would be genetically determined, we further hypothesized that in one kidney-one clip (1K-1C) rats, the response to stimulation of the renal alpha 2a/d-subtype would be intact as compared to the normotensive Wistar 1K-sham rats. 3. Male rats were unilaterally nephrectomized under ether anaesthesia. In the 1K-1C rats, a silver clip (diameter 0.254 mm) was also placed around the left renal artery. On the experimental day, rats were administered pentobarbitone (50.0 mg kg-1, i.p.). The carotid artery and jugular vein were cannulated for blood pressure monitoring and saline infusion. The ureter was catheterized for urine collection. A 31 gauge needle was advanced into the renal artery for infusion of the alpha 2a/d-selective agonist, guanfacine (vehicle, 1.0, 3.0 and 10.0 nmol kg-1 min-1 in Wistar and SH rats; vehicle and 10.0 nmol kg-1 min-1 in Wistar 1K-sham and 1K-1C rats). 4. In Wistar rats, guanfacine dose-dependently increased urine flow and sodium excretion. An increase in osmolar clearance but not free water clearance was also observed. However, in SH rats guanfacine failed to alter urine flow, sodium excretion, osmolar and free water clearance. In contrast, in both Wistar 1K-sham and 1K-1C rats, guanfacine increased urine flow rate. Again, this response was due solely to an increase in osmolar clearance. At these doses, guanfacine did not alter blood pressure or creatinine clearance during the experiment. 5. In summary, the ability of the alpha 2a/d-adrenoceptor subtype to mediate an increase in osmolar clearance was absent in a genetic model of hypertension, the SH rats. This effect was intact in an acquired model of hypertension (1K-1C rats). This suggested a defective modulation of solute excretion in SH rats which was probably due to alteration of the alpha 2a/d-subtype gene and not secondary to the elevated blood pressure. The altered alpha 2a/d-subtype gene and function may therefore play a causal role in the pathogenesis of hypertension.

Adrenergic alpha-Agonists↗
PubMed1997

Improved bioavailability and clinical response in patients with chronic liver disease following the administration of a spironolactone: beta-cyclodextrin complex.

AIMS: To compare the absorption and clinical effect of spironolactone from an inclusion complex with beta-cyclodextrin (SP-COMP) to Aldactone tablets (ALD) in chronic liver disease. METHODS: Patients, admitted with chronic liver disease, completed a randomized crossover steady state study. They received their spironolactone dose as either daily SP-COMP or ALD for 7 days. Serial blood samples were drawn over a 24 h period from day 7 of each therapy. Accurate fluid balance was recorded on days 5-7 and 12-14. Thirteen (six females) whose mean (s.d.) age and weight was 58.4(9.3) years and 74.3(19.0) kg completed the study. RESULTS: The mean (95% confidence limits) relative bioavailability for SP-COMP (compared with ALD) from steady state serum concentrations of canrenone, 6beta-hydroxyl 7alpha-thiomethyl spironolactone and 7alpha-thiomethyl spironolactone was 310.0 (265.4, 336.7), 233.4(212.9, 250.8) and 254.8(230.8, 279.0)%, respectively. Improvements in clinical status and fluid balance occurred over the last 3 days of SP-COMP with a mean (s.d.) net loss, in fluid balance, of 1370(860)ml compared with a gain of 228(936)ml during ALD. CONCLUSIONS: Better absorption of spironolactone from the spironolactone: beta-cyclodextrin complex formulation should lead to a reduction in dosage and perhaps a more consistent effect in patients with chronic liver disease.

Biological Availability↗
PubMed2001

Usefulness of forced diuresis for acute boric acid poisoning in an adult.

BACKGROUND: Boric acid is generally not recognized as a poisonous substance. However, boric acid has potentially fatal actions such as hypotension, metabolic acidosis and oliguria. Death may result from circulation collapse and shock. OBJECTIVE: We present a clinical case history of the successful use of forced diuresis with furosemide and intravenous fluid for boric acid poisoning. SUBJECT: A 26-year-old female who attempted suicide by consuming a large quantity of boric acid. She was brought to the hospital in a state of clouded consciousness, fever and erythema 14 h after ingestion. METHOD: 3.25 L of intravenous fluid and 100 mg of furosemide were administered over a period of 4 h in the intensive care unit and the serum and urinary concentrations of boric acid measured. RESULTS: The elimination rate of boric acid obtained with diuresis was similar to that obtained with haemodialysis on a previous occasion when the same patient attempted suicide with boric acid. The patient showed only temporary emesis and diarrhoea along with erythema, and was moved to the general ward 4 h after admission. Although in the general ward the patient's fever persisted and nausea, vomiting and headache often recurred, possibly because of an insufficient dose of furosemide, the patient's condition steadily improved over the 64 h after admission. CONCLUSION: Forced diuresis without haemodialysis is recommended early after admission for boric acid poisoning.

Adult↗
PubMed2003

Standardization of the renogram technique for investigating the dilated upper urinary tract and assessing the results of surgery.

OBJECTIVE: To recommend a standard technique for the renographic evaluation of the dilated upper urinary tract, and for evaluating the results of surgery. METHODS: This review is an update of the previously recommended consensus report of the 9th International Symposium of Radionuclides in Nephrourology. RESULTS: State-of-the-art recommendations are detailed for standardizing common radionuclide investigations. CONCLUSIONS: Where open, laparoscopic or endourological techniques for treating pelvi-ureteric junction obstruction are under study, results can only be compared by standardizing the investigational techniques. The guidelines produced here are recommended for this purpose.

Adolescent↗
PubMed2001

Management issues in toxicology.

The lack of evidence-based information in toxicology results in debate and differing recommendations on management issues. Gastric lavage is often utilized to remove toxins from the stomach but a clinical benefit of the procedure has not been definitively demonstrated. A selective approach is warranted in each patient, and gastric lavage can be considered in patients with life-threatening ingestions if it can be performed within 60 minutes of ingestion. Whole bowel irrigation is a method of GI decontamination utilizing isotonic electrolyte solution. Although safe, there is currently insufficient data to establish definite indications for use. This technique can be considered for potentially toxic ingestions of lithium, iron, and sustained-release or enteric-coated drugs. Multiple-dose activated charcoal has been used to enhance elimination of drugs already absorbed into the body but the optimum dose and frequency of administration is not established. Based on volunteer studies and limited clinical reports, multiple-dose activated charcoal may be considered in patients with life-threatening ingestions of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. A variety of interventions in addition to hemodialysis have been proposed to enhance lithium elimination. Forced saline diuresis and diuretics are not indicated. Although studies suggest that sodium polystyrene sulfonate may enhance elimination of lithium, no beneficial effects on clinical outcomes have been demonstrated and potential complications include hypokalemia and hypernatremia. Blood alkalinization for cyclic antidepressant toxicity has become standard therapy. Alkalinization is most effective in treating significant cardiac toxicity. Sodium bicarbonate, rather than hyperventilation, should be used initially to alkalinize blood. The benefit of blood alkalinization in the treatment of hypotension and seizures is not established.

Journal Article↗
PubMed2001

[Acute renal failure due to rhabdomyolysis in McArdle's disease following binge drinking with seizures].

HISTORY AND ADMISSION FINDINGS: A 36-year-old gardener was admitted for tonic-clonic seizures after binge drinking. The next days he developed massive rhabdomyolysis with acute renal failure. Past medical history was unremarkable except for a similar episode of acute renal failure 14 years ago. At that time he had consumed alcohol as well. Furthermore, the patient complained of exercise-related painful muscle cramping and swelling. INVESTIGATIONS: The serum creatinine peaked at 8.5 mg/dl, blood urea at 126 mg/dl and the maximal level of serum creatinine kinase was 108 300 U/l. Because of the massive rhabdomyolysis and the patient inverted question marks past medical history a metabolic myopathy was suspected and a muscle biopsy was performed. Histochemical staining of muscle frozen sections for phosphorylase revealed no activity which is typical for myophosphorylase deficiency (McArdle inverted question marks disease). Additional biochemical analysis of the muscle biopsy specimen confirmed the diagnosis. TREATMENT AND COURSE: By vigorous intravenous hydration and forced alkaline diuresis, the patient had a sufficient urinary output and lacked uremic signs. The serum creatinine and urea fell continuously and reached normal levels after 6 weeks. At that time serum creatinine kinase was still elevated (867 U/l), which is typical for McArdle inverted question marks disease. Avoiding alcohol, a new episode of rhabdomyolysis and acute renal failure did not occur. CONCLUSIONS: Besides exercise alcohol is likely to be a further possible trigger of rhabdomyolysis and acute renal failure in McArdle inverted question marks disease. Postulated mechanisms by which alcohol induces muscle injury include direct muscle toxicity and inhibition of gluconeogenesis, as these patients are probably more dependent on the gluconeogenetic pathway for muscle cell metabolism.

Acute Kidney Injury↗