A complicated chinese herbal medicine nephrotoxicity.

Chinese herbal medicine is widely used globally. In many instances, it is associated with severe adverse outcomes. We report case of a Chinese herbal nephropathy occurring in a 43-year-old woman showing renal impairment, metabolic acidosis, Stokes - Adams syndrome, hypernatremia, and hypokalemia, characteristics not usually encountered in published cases.

Acute hypernatremia exerts an inhibitory oxytocinergic tone that is associated with anxiolytic mood in male rats.

Anxiety disorders are the most common psychiatric illnesses and are associated with heightened stress responsiveness. The neuropeptide oxytocin (OT) has garnered significant attention for its potential as a treatment for anxiety disorders; however, the mechanism mediating its effects on stress responses and anxiety is not well understood. Here we used acute hypernatremia, a stimulus that elevates brain levels of OT, to discern the central oxytocinergic pathways mediating stress responsiveness and anxiety-like behavior. Rats were rendered hypernatremic by acute administration of 2.0 M NaCl and had increased plasma sodium concentration, plasma osmolality, and Fos induction in OT-containing neurons relative to 0.15 M NaCl-treated controls. Acute hypernatremia decreased restraint-induced elevations in corticosterone and created an inhibitory oxytocinergic tone on parvocellular neurosecretory neurons within the paraventricular nucleus of the hypothalamus. In contrast, evaluation of Fos immunohistochemistry determined that acute hypernatremia followed by restraint increased neuronal activation in brain regions receiving OT afferents that are also implicated in the expression of anxiety-like behavior. To determine whether these effects were predictive of altered anxiety-like behavior, rats were subjected to acute hypernatremia and then tested in the elevated plus maze. Relative to controls given 0.15 M NaCl, rats given 2.0 M NaCl spent more time in the open arms of the elevated plus maze, suggesting that acute hypernatremia is anxiolytic. Collectively the results suggest that acute elevations in plasma sodium concentration increase central levels of OT, which decreases anxiety by altering neuronal activity in hypothalamic and limbic nuclei.

Pilot randomised double-blind controlled trial of high-dose spironolactone in critically ill patients receiving a frusemide infusion.

BACKGROUND: Hypernatraemia may develop during intravenous infusion of frusemide. Spironolactone is an aldosterone antagonist that promotes natriuresis and may attenuate such hypernatraemia, but its effect in this setting has not been previously studied. OBJECTIVE: To assess whether the administration of spironolactone to ventilated patients receiving a frusemide infusion attenuates the increase in serum sodium concentration. DESIGN AND SETTING: Randomised, double-blind, placebo-controlled trial (January 2005 to December 2006). PATIENTS: 20 patients with a serum creatinine concentration < 300 micromol/L who were undergoing mechanical ventilation in the intensive care unit and had begun a frusemide infusion as treatment for fluid overload within the previous 24 hours. METHODS: Patients were randomly allocated to receive either spironolactone (100 mg three times daily) or placebo by nasogastric tube for the duration of the frusemide infusion. Daily serum levels of urea and creatinine, 24-hour urine sodium and potassium levels, fluid balance and 24- hour blood levels of aldosterone, human atrial natriuretic peptide and plasma renin activity were measured throughout the period of frusemide infusion. RESULTS: Change in serum sodium concentration over 48 hours from baseline was 3.0 mmol/L for placebo versus 1.0 mmol/L for the spironolactone group (P = 0.08). Change in serum potassium concentration did not differ between the groups (0.125 mmol/L over 48 hours). There were no significant differences in total urinary sodium or potassium excretion. Serum creatinine, urea, urine volume, fluid balance, potassium requirements and hormone levels were similar in both groups. CONCLUSIONS: In this pilot study, the administration of high-dose spironolactone to ventilated critically ill patients receiving frusemide by infusion had no significant effects on serum sodium level, natriuresis or potassium balance when compared with placebo.

Severe hyperphosphatemia and hypocalcemia following the rectal administration of a phosphate-containing Fleet pediatric enema.

BACKGROUND: Toxicity secondary to rectally administered hypertonic phosphate solution in patients with normal renal function is rarely reported in the literature. We report a case of electrolyte disturbance and seizure secondary to the rectal administration of 2 Fleet pediatric enemas. CASE REPORT: A 4-year-old white female with spinal muscular atrophy and chronic constipation was brought to the emergency department with complaints of lethargy and difficulty breathing following the administration of 2 Fleet pediatric enemas. In the emergency department, physical examination was significant for a depressed level of consciousness and shallow respirations. A basic metabolic profile was significant for a calcium of 3.3 mg/dL, phosphate of 23 mg/dL, and sodium of 153 mEq/L. Arterial blood gases revealed a pH of 7.24, Pco2 of 38 mm Hg, Po2 of 220 mm Hg. Electrocardiogram revealed a prolonged QT interval of 340 milliseconds with a corrected QT interval of 498 milliseconds. Sixteen hours postexposure, she experienced a generalized seizure unresponsive to multiple doses of lorazepam and responsive only to 100 mg of intravenous calcium chloride. Two days after presentation, the patient experienced complete resolution of symptoms. CONCLUSION: Osmotically acting hypertonic phosphate enemas can result in severe toxicity if retained. This is true even in patients without predisposing risk factors.

Effect of sodium alterations on hepatic cytochrome P450 3A2 and 2C11 and renal function in rats.

Numerous dietary supplements are known to modulate cytochrome P450 (CYP)-mediated metabolism and subsequently alter drug toxicity or efficacy in animals and humans. In the present study we investigated the effect of varying amounts of sodium intake on renal function and the metabolic activity of the hepatic CYP3A2 and CYP2C11 isoforms. Rats were maintained on standard rodent chow or a low-salt rice diet. Within each of these groups rats received either a single intraperitoneal injection of furosemide to initiate salt depletion, or saline. Additional groups included salt supplementation of 500 mg/300 g body weight/day and 1.25 g/300 g body weight/day of sodium chloride solution. Rats receiving the low-salt diet, both with and without a concomitant furosemide administration, had a significant reduction in creatinine clearance without changes in serum creatinine. In addition, urine flow rate was markedly reduced in rats maintained on the low-salt diet. Western blot analysis indicated that neither sodium supplementation nor deprivation altered hepatic microsomal CYP3A2 levels; however, hepatic CYP2C11 levels significantly increased in rats receiving the largest sodium supplement. In vitro metabolic activity of CYP3A2 was unchanged as compared with controls. Activity of CYP2C11 was significantly reduced in both rat groups receiving additional sodium supplements. Acute manipulation of daily sodium intake does alter renal function and specific hepatic CYP isoforms and should be considered when using these rat models.

Effect of ethanolic extract of Khaya senegalensis on some biochemical parameters of rat kidney.

The effect of administration of ethanolic extract of Khaya senegalensis (2mg/kg body weight) on some biochemical parameters of rat kidney were investigated. Experimental animals were randomly divided into the control, those administered with the extract for 6 days and those administered with extract for 18 days, respectively. The prolonged administration of the extract resulted in significant reduction in the alkaline phosphatase activities of the kidney and its body weight ratio (P<0.05). In contrast, the same prolonged administration of the extract resulted in significant increase in the serum sodium ion concentration (P<0.05) while there was no significant difference in serum potassium ion concentration when compared to control (P>0.05). Administration of the extract for 6 days produced no significant difference from the control values in all the parameters investigated except in serum urea concentration which produced a significant increase (P<0.05). The available evidence in this study suggest that the ethanolic extract of Khaya senegalensis exerted more deleterious effect on the kidney when administered continuously over a prolonged period than a short one and this will adversely affect the functioning of the kidney.

Baking soda: a potentially fatal home remedy.

We present a case of a six-week-old infant who developed life-threatening complications after unintentional sodium bicarbonate intoxication. Baking soda was being used by the mother as a home remedy to "help the baby burp." A review of the literature regarding the use (or misuse) of baking soda follows. Our patient, along with the other noted case reports, emphasizes the need for warnings on baking soda products whose labels recommend its use as an antacid. Poisonings must be high in the differential diagnosis of any patient, regardless of age, who presents with altered mental status or status epilepticus.

Glucose polymers in diarrhoea--risk of hypernatraemia.

An infant girl with congenital heart disease was fed glucose polymers as dietary supplements. During an attack of gastroenteritis with severe diarrhoea she developed hypernatraemic dehydration, probably due to the high osmotic load of the glucose polymers. This case illustrates the importance of giving adequate amounts of free water to a child on glucose polymers, especially during excessive fluid loss.

Vasopressin transport regulation is coupled to the synthesis rate.

Vasopressin is synthesized in the perikarya of magnocellular neurons and is transported down long axons to the storage terminals of the posterior pituitary. To maintain stable pituitary stores following vasopressin secretion, the hypothalamus must synthesize and transport an amount of new vasopressin, equivalent to the amount released. Vasopressin release and synthesis rate can be chronically upregulated or suppressed relative to basal levels, depending on the demand for vasopressin. We studied whether vasopressin transport was similarly regulated during situations of varying demand. During chronic hyponatremia, when synthesis of vasopressin was reduced to undetectable levels, transport of vasopressin was also markedly decreased, as evidenced by continued presence of vasopressin in the transport system. Upregulation of transport was demonstrated by measuring pituitary accumulation of vasopressin in rats whose pituitary stores were initially depleted by hypernatremia and in whom subsequent release was suppressed by hyponatremia. In hypernatremic rats, transport of vasopressin was increased fivefold over baseline as determined by pituitary accumulation, and this elevated rate persisted for 7 days in the absence of release. This study demonstrates that axonal transport of vasopressin is a regulated process and is linked to synthesis rate rather than release.

Hyperosmolality due to antacid treatment.

Magnesium trisilicate mixture is an antacid used commonly in our Intensive Care Unit in the prevention and treatment of stress ulcers. In this case the administration of large doses over a period of time led to the development of massive hyperosmolality, cerebral dehydration and coma. Management with hypotonic fluid resulted in complete recovery.