Ammonium Chloride Ingestion Research Articles

Effects of ammonium chloride ingestion on phosphocreatine metabolism during moderate- and heavy-intensity plantar-flexion exercise

This study examined the effects of NH(4)Cl ingestion on phosphocreatine (PCr) metabolism during 9 min of moderate- (MOD) and heavy- (HVY) intensity constant-load isotonic plantar-flexion exercise. Healthy young adult male subjects (n = 8) completed both a control (CON) and NH(4)Cl ingestion (ACID) trial. Phosphorus-31 magnetic resonance spectroscopy was used to monitor changes in intracellular pH (pHi), [Pi], [PCr], and [ATP]. During the Middle (3-6 min) and Late (6-9 min) stages of HVY, ACID was associated with a higher (P < 0.05) intracellular hydrogen-ion concentration ([H(+)]i) [Middle: 246 (SD 36) vs. 202 (SD 36) mmol/l]; [Late: 236 (SD 35) vs. 200 (SD 39) mmol/l]. In addition, ACID was associated with a lower (P < 0.05) [PCr] relative to CON during the Early (0-3 min) [18.1 (SD 5.1) vs. 20.4 (SD 5.4) mmol/l] and Middle stages [14.1 (SD 5.4) vs. 16.7 (SD 6.0) mmol/l] of HVY. The amplitude of the primary component of PCr breakdown during the transition to HVY was greater in ACID than CON [14.5 (SD 5.8 vs. 11.3 (SD 4.8) mmol/l], however, the PCr slow component (continued slow decline in [PCr]) showed no difference (P > 0.05). The time constant for PCr breakdown (tauPCr) was greater in HVY than MOD for both conditions [58 (SD 22) vs. 28 (SD 15) s ACID; 51 (SD 20) vs. 29 (SD 14) s CON] (P < 0.05). In summary, ACID increased PCr breakdown during the transition from MOD to HVY, but did not increase the magnitude of the PCr slow component.

A complicated hospitalization following dilute ammonium chloride ingestion

Unintentional ingestions of dilute (<7.5%) cleaning solutions containing ammonium chloride typically do not cause serious harm. We present a case of an intentional ingestion of a dilute ammonium chloride solution resulting in significant morbidity. A 60-year-old woman with bipolar disorder presented one hour after an intentional ingestion of approximately 15 fluid ounces (500 mL) of an algae and odor humidifier treatment containing a total of 2.25% ethyl ammonium chloride. Initial complaints included nausea with a single episode of nonbilious, nonbloody emesis, mild shortness of breath, and chest and epigastric pain. Physical exam was remarkable for bilateral wheezing and epigastric tenderness. An emergent endoscopy demonstrated a Grade 2b caustic injury in the esophagus and a Grade 3b injury in the stomach. Due to persistent cough, copious oral secretions, and worsening hoarseness, the patient was intubated and admitted to the ICU. Her course was complicated by mild hypotension, nonanion gap metabolic acidosis, and oliguria treated successfully with intravenous (IV) fluids. She also developed bilateral pneumonias later in the hospital course. Bedside bronchoscopy showed laryngeal edema and mucosal injury to the segmental level. The patient underwent tracheostomy on hospital day 6. An upper GI swallow study revealed poor esophageal motility in the mid- to lower third of the esophagus. The patient gradually tolerated oral fluids and on hospital day 20 had her tracheostomy tube removed. The patient was subsequently transferred to the psychiatric ward on hospital day 22. Intentional ingestions of dilute ammonium chloride solutions can cause serious injury to the gastrointestinal tract and pulmonary systems, which can result in a complicated and prolonged hospitalization.

Effect of ammonium chloride and dietary phosphorus in the azotaemic rat. I. Renal function and biochemical changes.

Both dietary phosphorus restriction and the ingestion of ammonium chloride (NH(4)Cl) given to rats on a high-phosphorus diet have been shown to preserve renal function in the azotaemic rat. Parathyroidectomy also has been reported to preserve renal function and, in addition, to prevent kidney hypertrophy in the remnant kidney model. Our goals were (i) to evaluate in azotaemic rats the effect of dietary phosphorus on renal function in a shorter time frame than previously studied and (ii) to determine whether NH(4)Cl administration (a) enhances the renoprotective effect of dietary phosphorus restriction and (b) improves renal function in the absence of parathyroid hormone (PTH). High (H; 1.2%), normal (N; 0.6%) and low (L; <0.05%) phosphorus diets (PD) were given for 30 days to 5/6 nephrectomized rats. In each dietary group, one-half of the rats were given NH(4)Cl in the drinking water. The six groups were HPD + NH(4)Cl, HPD, NPD + NH(4)Cl, NPD, LPD + NH(4)Cl and LPD. The effect of NH(4)Cl administration was also evaluated in 5/6 nephrectomized, parathyroidectomized (PTX) rats on NPD. In each of the three dietary phosphorus groups, creatinine and urea clearances were greater (P<0.01) in rats receiving NH(4)Cl. Neither creatinine nor urea clearance was reduced by high dietary phosphorus. Urine calcium excretion was greatest in the LPD group and was increased (P < or = 0.001) in all three groups by NH(4)Cl ingestion. An inverse correlation was present between plasma calcium and phosphorus in the parathyroid intact (r = -0.79, P<0.001) and PTX groups (r = -0.46, P = 0.02). In PTX rats, NH(4)Cl ingestion increased (P < or = 0.01) creatinine and urea clearances and both an increasing plasma calcium concentration (r = 0.67, P<0.001) and urine calcium excretion (r = 0.73, P<0.001) increased urine phosphorus excretion. At 30 days of renal failure (i) NH(4)Cl ingestion increased creatinine and urea clearances, irrespective of dietary phosphorus; (ii) high urine calcium excretion, induced by dietary phosphorus restriction and NH(4)Cl ingestion, did not adversely affect renal function; (iii) high dietary phosphorus did not decrease renal function; (iv) the absence of PTH did not preserve renal function or prevent NH(4)Cl from improving renal function; and (v) both an increasing plasma calcium concentration and urine calcium excretion resulted in an increase in urine phosphorus excretion in PTX rats.

Clinical efficacy of L-ornithine-L-aspartate in the management of hepatic encephalopathy.

The clinical efficacy of both oral and parenteral L-ornithine-L-aspartate (OA) was confirmed by randomized, placebo-controlled, double-blind studies in patients with manifest hepatic encephalopathy and hyperammonemia. The drug was able to reduce high blood ammonia levels induced either by ammonium chloride or protein ingestion or existing as a clinical complication of cirrhosis per se. Furthermore, OA improved performance in Number Connection Test-A as well as mental state gradation. In contrast to the positive effects observed in patients with more advanced hepatic encephalopathy, oral OA does not seem to affect minimal hepatic encephalopathy. In a recent trial, OA decreased protein breakdown and stimulated protein synthesis in muscle. The therapy had little side effects, increasing with higher intravenously administered dosages, and was well tolerated after oral and parenteral administration.

Reversible nephrotoxicity of onconase and effect of lysine pH on renal onconase uptake.

To examine the histopathology of the kidney in mice following repeated injections of the antitumor drug onconase, and to determine whether lysine, which reportedly blocks kidney uptake of other basic proteins, blocks the high renal uptake of onconase. Mice received repeated intraperitoneal onconase injections over 3 weeks. Kidneys were examined by light microscopy after 1 week, 3 weeks, and 5 weeks (2 weeks after cessation of injections) and compared to kidneys from animals receiving a similar schedule of PBS injections. Renal uptake of radioiodinated onconase was measured in animals receiving intraperitoneal injections of lysine solutions of acidic and neutral pH given at -30, 0 and + 5 min relative to intravenous onconase injection. Renal onconase uptake was also measured in animals made metabolically acidotic by ingestion of ammonium chloride, arginine chloride or lysine dihydrochloride from the drinking water. Onconase caused acute moderate multifocal proximal renal tubular necrosis, and this toxicity was reversed by 2 weeks after drug withdrawal. Intraperitoneal injections of lysine dihydrochloride in PBS (pH 1.5) reduced renal onconase uptake at 15 min from 67.9+/-13.4% to 17.0+/-3.8% of the injected dose without affecting the plasma concentration and also reduced the fraction of degraded onconase in the urine. However, neutral solutions of lysine dihydrochloride at pH 7.4 or lysine acetate at pH 7.1 were ineffective at blocking renal onconase uptake. Furthermore, renal onconase uptake was minimally or not affected by a state of metabolic acidosis. Proximal tubular toxicity of onconase was reversible. Renal onconase uptake was blocked by lysine at pH 1.5 but not at neutral pH.

Enhanced Na(+)-H+ exchanger activity and NHE-1 mRNA levels in human lymphocytes during metabolic acidosis.

It has recently been demonstrated that uremic metabolic acidosis and experimental metabolic acidosis caused by ingestion of ammonium chloride coincide with increased Na(+)-H+ exchanger (NHE-1) activity in human blood cells. In the present study, we investigated whether an increased level of NHE-1 specific mRNA in human lymphocytes during the course of an experimental metabolic acidosis could explain the enhanced transport activity during metabolic acidosis. Six healthy individuals were studied before and after 5 days of taking 15 g of ammonium chloride daily. Plasma pH and bicarbonate decreased significantly, from 7.42 +/- 0.027 to 7.28 +/- 0.05 and from 26.7 +/- 2.0 to 15.6 +/- 2.9 mM, respectively. Basal cytosolic pH (pHi) and Na(+)-H+ exchange activity were measured in lymphocytes loaded with the fluorescent pHi indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Basal pHi remained unchanged during metabolic acidosis (7.03 +/- 0.07 vs. 7.03 +/- 0.06). Ethylisopropylamiloride-sensitive pHi recovery increased from 0.046 +/- 0.007 to 0.076 +/- 0.012 dpHi/min (P < 0.0001). The transcript level of NHE-1 mRNA was measured by reverse-transcription polymerase chain reaction in comparison with a constitutively expressed reference gene (glyceraldehyde-3-phosphate dehydrogenase). NHE-1 mRNA in human lymphocytes increased 1.5-fold in metabolic acidosis. These data suggest that the increased Na(+)-H+ exchange activity in metabolic acidosis may be caused by de novo synthesis of antiport protein.

Metabolic acidosis inhibits growth hormone secretion in rats: mechanism of growth retardation

To test the hypothesis that growth retardation in nonanion gap acidosis may be associated with impairment of growth hormone (GH) secretory patterns, we examined GH secretion in rats made acidotic with ammonium chloride ingestion. Considerable growth retardation was demonstrated in pair-fed and acidotic rats after 1 wk of ammonium chloride ingestion compared with control. With stable metabolic acidosis sustained on the 8th day of experiment, pulsatile secretion of GH was evaluated by blood samples drawn every 10 min for 6 h. Using deconvolution analysis to quantitate in vivo GH secretory rates, we found significant inhibition of pulsatile GH secretion in acidotic rats. Changes in amplitude of GH pulses and mean mass of GH pulses correlated with changes in body weight. These studies showed that chronic metabolic acidosis causes growth impairment, reduced food efficiency, and amplitude-specific inhibition of pulsatile secretion of GH. We propose that this GH axis suppression, whether mediated by decreased nutrients or not, contributes significantly to growth failure in children with renal tubular acidosis. Because a similar degree of inhibition of GH secretion was seen in pair-fed rats, we infer that insufficient calorie intake in metabolic acidosis may contribute to disruption of normal GH secretion patterns. These changes in GH secretion were specific, because acidotic rats were different from pair-fed controls in that they showed no change in either half-life of GH in circulation or in pulse frequency. Such observations offer a rationale for more detailed clinical investigations into the impact of metabolic acidosis on physiological regulation of pulsatile GH secretion in humans.

Effects of prior exercise or ammonium chloride ingestion on muscular strength and endurance.

Previous studies linked muscular fatigue with a decrease in blood pH. This study investigated if the means of altering pH affected the extent of muscular fatigue. Drug-induced and exercise-induced acidosis were compared to test the hypothesis that exercise-induced acidosis impairs subsequent muscular performance more than chemically induced acidosis. In eight male subjects acidosis was induced by ingesting 0.3 g.kg-1 ammonium chloride (AC) for one trial, by upper body exercise (UBE) for another trial, and after placebo (PL) treatment. They then completed a performance test (PT) of 50 maximal, bilateral isokinetic knee extensions. Whole blood pH before (pHpre) and after (pHpost) the PT was 7.412, 7.264, and 7.261 for PL, UBE, and AC, respectively; both AC and UBE decreased pH similarly compared with PL. Peak torque and total work during the PT were similar for PL and AC, and were significantly greater than after UBE. Six subjects performed a fourth trial after combined AC and UBE treatments causing a pHpre of 7.081, but there was no greater performance impairment than that caused by UBE alone. The results dissociate the extent of the impairment from the magnitude of the disruption in blood pH.

Plasma ammonia is the principal source of ammonia in sweat.

Sweat contains ammonia. However, neither its source nor factors affecting its concentration in the sweat are known. The aim of this study was to examine the effect of plasma concentrations of ammonia and urea on the concentration of ammonia in the sweat. Four groups of male volunteers were examined: one control, two after ingestion of ammonium chloride, three cirrhotic, hyperammonaemic, four uraemic. Sweat was collected from each subject from the palmar side of the forearm using gauze pads, after previous iontophoresis of pilocarpine. Ammonia and urea concentrations were determined in the sweat and in the plasma. It was found that elevated plasma ammonia concentration in healthy subjects after ingestion of ammonium chloride as well in the cirrhotic patients resulted in an increase of ammonia concentration in the sweat. High plasma and sweat urea concentration in the uraemic subjects did not affect the concentration of ammonia in the sweat. It was concluded that plasma ammonia was the principal source of ammonia in the sweat.

Comparison of Patients with Idiopathic Calcium Phosphate and Calcium Oxalate Stones

Our primary objective was to test the hypothesis that a defect in acidification is more common in patients who have idiopathic calcium phosphate kidney stones than in those whose stones are formed mainly of calcium oxalate. Additionally, other risk factors might differ for these 2 stone types. Urine pH was measured serially over 24 hours, and along with ammonium and titratable acid, it was measured before and serially after ingestion of ammonium chloride in 3 groups of subjects: 24 patients with predominantly calcium phosphate stones, 30 patients with calcium oxalate stones, and 15 health non-stone-formers. Twenty-six parameters potentially related to stone formation and acidification were assayed on urines collected over 24 hours, and 15 parameters on blood. The data base was a computerized list of 5900 analyses of stones from patients living in Newfoundland. Patients not known by their physician to have had urinary tract infection, anatomical abnormality, hyperparathyroidism, or renal tubular acidosis were asked to participate in the study. Differences between means were considered significant if p values were less than 0.05 for F by analysis of variance and also less than 0.01 by t-test. In all patients with calcium oxalate stones and all non-stone-formers, urine acidified to pH less than 5.25, but in 8 of the 23 phosphate stone formers who completed the ammonium chloride study urine failed to acidify to pH less than 5.25. As all 8 had normal values for venous pH, total CO2, and chloride, they were considered to have incomplete renal tubular acidosis (IRTA). The 8 phosphate stone formers with IRTA had greater mean values for urine pH on all 9 specimens collected serially over 24 hours (all means greater than 6.2), and after administration of ammonium chloride (p less than 0.01), as well as lower mean values for urine titratable acid excretion (p less than 0.01), both after administration of ammonium chloride and in 24-hour urine samples, compared with the remaining phosphate stone formers whose urine acidified and the oxalate and non-stone-forming control groups. Nearly all the phosphate stone formers had 1 or more risk factors for stone formation, but with frequencies not significantly higher than those found in the oxalate group. Hypercalciuria and hypocitruria were the commonest, but increased oxalate or urate also occurred. Thus, idiopathic calcium phosphate stone formation can be associated with 1 or more of several risk factors, and, with the possible exception of those with IRTA, treatment should be similar to that given to patients with calcium oxalate stones.

Responses to Excess Dietary Magnesium as Affected by Experimental Eimeria acervulina Infection or by Dietary Ammonium Chloride Ingestion in the Chick

Three experiments were conducted to investigate the effect of experimental Eimeria acervulina infection on excess Mg ingestion in the chick and to investigate the effect of NH4Cl addition to the diet on the coccidiosis × Mg interaction. Two Mg sources were evaluated, MgO and MgSO4·7H2O. Gain, efficiency of feed utilization, bone ash percent (BAP), bone Ca and duodenal pH were lower in coccidiosis-infected chicks than in uninfected chicks. However, bone P and bone Mg levels were higher as a result of the coccidial infection. Bone Mg levels were higher and bone Ca levels and BAP were lower in chicks fed excess dietary Mg, either as the oxide or sulfate forms. Gain and feed efficiency of chicks fed excess Mg, as MgO but not as MgSO4·7H2O, were lower than in chicks fed the basal level of Mg. Coccidiosis × Mg interactions were observed in bone Mg and bone Ca concentration data; bone Mg uptake was greater when high dietary Mg and the coccidial infection were in combination. In some instances, a similar interactive effect was observed in bone Ca concentration data; bone Ca loss tended to be greater as a result of the combination of high dietary Mg and the coccidial infection.

Chronic metabolic acidosis augments acidification along the inner medullary collecting duct.

The inner medullary collecting duct (IMCD) of the rat is a major site of acidification. However, previous micropuncture studies have failed to demonstrate acidification along the terminal IMCD during chronic acid feeding. To more completely evaluate this question we used the microcatheterization method in rats fed ammonium chloride for 3-7 days. Arterial pH was 7.30 +/- 0.015, and PCO2 was set at 40 +/- 0.6 mmHg. The IMCD data were analyzed as a function of IMCD length between 40% and the tip. Equilibrium pH decreased from 6.21 +/- 0.11 to 5.47 +/- 0.03, whereas PCO2 was unchanged (28 +/- 1 mmHg between the deep samples and tip). Bicarbonate delivery decreased from 92 +/- 14 to 10 +/- 1 nmol/min, titratable acid increased from 462 +/- 33 to 762 +/- 40 nmol/min, and ammonium delivery increased from 2,235 +/- 121 to 3,528 +/- 140 nmol/min. Thus estimated net acid increased from 2,638 +/- 134 to 4,303 +/- 161 nmol/min. To determine whether increasing delivery of buffer to the IMCD would stimulate acid secretion in acute acidosis, rats were studied during the infusion of HCl and creatinine. Arterial pH was 7.18 +/- 0.02. IMCD acidification was not increased compared with our previously published studies during HCl infusion [Am. J. Physiol. 241 (Renal Fluid Electrolyte Physiol. 10): F669-F676, 1981]. We conclude that chronic ammonium chloride ingestion stimulates IMCD acidification and that this increase may be an intrinsic modification of the acidification mechanism of the IMCD.

Effect of chronic metabolic acidosis on vitamin D metabolism in humans

AbstractEffect of chronic metabolic acidosis on vitamin D metabolism in humans. Bone disease may occur in disorders associated with chronic metabolic acidosis. This has been attributed, in part, to reduced production of 1,25(OH)2D3. Although metabolic acidosis in the vitamin D deficient animal has been associated with a reduction in the conversion of radiolabeled 25(OH)D3 to 1,25(OH)2D3, studies in D-replete humans have revealed no effect of acidosis on 1,25(OH)2D3 metabolism. To examine this issue further, we measured serum 25(OH)D, 1,25(OH)2D, and 24,25(OH)2D levels in six healthy subjects before and after 9 days of metabolic acidosis induced by the ingestion of ammonium chloride. In four subjects, we measured the increment in serum levels of 1,25(OH)2D in response to the infusion of parathyroid extract both during control and acidosis. Serum levels of 1,25(OH)2D, 13.6 ± 1.3 and 14.3 ± 0.9 pg/ml, in control and acidosis, respectively, were not different. The serum 1,25(OH)2D levels in control and acidosis rose to a similar degree with the infusion of PTE. These data provide strong evidence that metabolic acidosis does not have a substantial impact on the synthesis of 1,25(OH)2D3 metabolism in vitamin D-replete humans.Effet de l'acidose métabolique chronique sur le métabolisme de la vitamine D chez les humains. Une ostéopathie peut survenir lors des maladies associées à une acidose métabolique chronique. Cela a été en partie attribué à une diminution de production de 1,25(OH)2D3. Bien que l'acidose métabolique chez l'animal déficient en vitamine D ait été associée avec une diminution de la conversion de 25(OH)D3 radiomarquée en 1,25(OH)2D3, les études chez les humains réplété en vitamine D n'ont pas révélé d'effet de l'acidose sur le métabolisme de la 1,25(OH)2D3. Afin d'étudier ce point plus à fond, nous avons mesuré la 25(OH)D, la 1,25(OH)2D et la 24,25(OH)2D sériques chez six sujets normaux avant et après 9 jours d'acidose métabolique induite par l'ingestion de chlorure d'ammonium. Chez quatre sujets, nous avons mesuré l'augmentation des concentrations sériques de 1,25(OH)2D en réponse à la perfusion d'extraits parathyroïdiens pendant le contrôle et l'acidose. Les concentrations sériques de 1,25(OH)2D, 13,6 ± 1,3 et 14,3 ± 0,9 pg/ml, pendant le contrôle et l'acidose, respectivement, n'étaient pas différentes. Les concentrations sériques de 1,25(OH)2D pendant le contrôle et l'acidose se sont élevées d'une façon semblable pendant la perfusion avec la PTE. Ces données sont fortement en faveur du fait que l'acidose métabolique n'a pas d'impact substantiel sur la synthèse de 1,25(OH)2D3 chez les humains réplété en vitamine D.

Ammonia-induced changes in pancreatic hormones and plasma amino acids in patients with liver cirrhosis.

The contribution of hyperammonemia to plasma amino acid imbalance in patients with liver disease was assessed in 10 subjects with chronic hepatitis and in 17 advanced cirrhotics. Insulin, glucagon, and plasma amino acids were determined both in the basal state and 45 min after oral ammonium chloride, at doses used in the ammonia-tolerance test. In cirrhotics, ammonia increased to 3 times basal values, in association with a rise in insulin and, more marked, in glucagon. Aromatic amino acids and free tryptophan further increased, while a significant fall in branched-chain amino acids and glutamate was observed. The increase in ammonia levels strongly correlated with the increase in glucagon (r = 0.707). Two patients, with large esophageal varices, showed signs of disturbed consciousness, in association with a marked rise in ammonia and in the ration of free tryptophan to the sum of neutral amino acids. In patients with chronic hepatitis, whose ammonia levels rose slightly, minor variations in pancreatic glucoregulatory hormones and plasma amino acids were observed, as also happened in 10 healthy subjects following ammonium chloride ingestion. Our data fit with the hypothesis that the plasma amino acid imbalance of cirrhotics may be partly due to ammonia-induced changes in pancreatic hormones.

Renal tubular function in glycerol-induced acute renal failure

The purpose of this study was to examine proximal and distal tubular function in rats with nonoliguric, myohemoglobinuric acute renal failure (ARF). ARF was induced with glycerol (50%, 10 ml/kg of body wt, i.m.), and renal function was studied 24 hours after glycerol or saline (controls) injection. Glycerol injection caused a 50 to 90% depression in GFR and a significant rise in blood urea nitrogen concentration. Animals with ARF exhibited glycosuria with normal blood sugar levels and a striking depression in tubular glucose reabsorption per milliliter of GFR. The capacity to reabsorb (mEq/liter GFR) was intact at normal blood bicarbonate levels, but was markedly depressed when blood bicarbonate was raised. The tubular maximum for para-aminohippurate (PAH) secretion and the renal extraction fraction of PAH were strikingly depressed in rats with ARF. Distal acidification as assessed by the urine-to-blood gradient of PCO2 (UB PCO2) was normal both during maximal alkalinization of the urine with bicarbonate (urine pH, approximately 7.8) or during neural phosphate infusion (urine pH, approximately 7.0). Net acid excretion per milliliter GFR and minimal urine pH (less than 5.5) following 3 days of ammonium chloride ingestion was similar in control and ARF animals. Potassium excretion was intact in maximal urinary osmolality were significantly altered in animals with ARF. Cortical and outer medullary Na-K-ATPase specific activities were significantly depressed in ARF rats. This occurred as a consequence of enzyme loss and not secondary to alterations in enzyme kinetics of absolute tubular sodium reabsorption. Light and electron microscopy showed diffuse proximal tubular damage, whereas glomeruli and distal tubules were intact. These data demonstrate that glycerol injection produces a diffuse proximal tubular transport defect associated with histologic and enzymatic alterations.

Acid-induced osteoporosis: An experimental model of human osteoporosis

Adult animals, male or female, react to ammonium chloride ingestion with a non-hormonal, generalized, slow but progressive and unrelenting mobilization of bone and develop osteoporosis which seems indistinguishable in all parameters measured from human osteoporosis. (Table I).

Studies in osteoporosis: the long-term effect of oophorectomy and of ammonium chloride ingestion on the bone of mature rats.

Adult female rats were subjected to a prolonged period of observation after oophorectomy. The oophorectomized animals and their controls were given a regular diet ad lib and water or ammonium chloride as their drinking fluid. Oophorectomy did not result in reduced bone density, fat free weight, total ash weight, or calcium content of the bone, thus failing to produce the changes of osteoporosis. Ammonium chloride ingestion caused significant decreases in the same parameters equally in normal and oophorectomized rats. Thus, oophorectomy neither leads to changes of osteoporosis, nor increases the sensitivity of the bone to ammonium chloride-induced osteoporosis.

The Effect of Chronic Ammonium Chloride Ingestion on Parathyroid Hormone Function

The purpose of this study was to examine the effect of ammonium chloride ingestion on the hypercalcemic effect of parathyroid hormone in vivo. Thyroparathyroidectomized rats were given 1.5% ammonium chloride for 5-6 days. Ingestion of ammonium chloride increased serum calcium, but also significantly enhanced the calcium elevating effect of injected parathyroid extract. This result is compatible with a proposed hypothesis that the calcium mobilizing function of the parathyroid hormone may be enhanced by the hormone's own influence on systemic hydrogen ion concentration.

Metabolic and genetic studies of a family with ornithine transcarbamylase deficiency.

Extract: We have described a patient with ornithine transcarbamylase (OTC) deficiency. The clinical course and pedigree substantiate the X-linked transmission of the defect with varying degrees of illness in females. Because orotic aciduria accompanied hyperammonemia in the patient, orotic acid was measured as an indication of a partial OTG deficiency after ammonia and protein loading in members of the patient's family. Both the mother, an obligate carrier, and an aunt, the only symptomatic female in this pedigree, had hyperammonemia after the ingestion of ammonium chloride. They also had significant orotic aciduria after a protein load as did the two female cousins whose ammonium tolerance was normal. The maternal grandmother excreted a large amount of orotic acid in her urine relatively consistently. These data suggest that the two female cousins and the maternal grandmother are asymptomatic female heterozygotes despite their normal ammonium loading tests.Speculation: Protein loading in the form of a relatively palatable and innocuous meal, followed by determination of orotic acid content in urine, may prove to be a sensitive, noninvasive, and easy means to identify female carriers of ornithine transcarbamylase deficiency.

A study of the influence of pH on the buccal absorption and renal excretion of procainamide.

The buccal absorption of procainamide was studied in 4 normal, male volunteers over a pH range of 5–11. In another investigation the same 4 volunteers collected their urine for 24 h after taking 250 mg of procainamide hydrochloride orally on 3 separate occasions, during which urine pH was uncontrolled, acidified by ammonium chloride ingestion or alkalinised by sodium bicarbonate ingestion. The procainamide remaining after buccal absorption and present in the urine samples was determined spectrophotometrically. It was found that neither the buccal absorption nor the renal excretion of procainamide was substantially altered by changes in pH.