Administration Of Citric Acid Research Articles

Potential of Alkalization Therapy for the Management of Metastatic Pancreatic Cancer: A Retrospective Study.

Current treatments for patients with pancreatic cancer offer limited benefits. In this study, we applied alkalization therapy, which was efficacious for other solid tumors at our clinic, to stage 4 pancreatic cancer patients, and investigated its effect on disease prognosis. Patients with metastatic pancreatic cancer who were treated at Karasuma Wada Clinic in Kyoto, Japan, between January 2011 and April 2022, were included in the study. All patients received alkalization therapy (a combination of an alkaline diet, bicarbonate, and citric acid administration), alongside standard chemotherapy. Urine samples were collected to assess urine pH as a marker of whole-body alkalization. In the 98 patients analyzed, the median overall survival (OS) from the time of diagnosis was 13.2 months. Patients with a mean urine pH of 7.5 or greater had a median OS of 29.9 months, compared with 15.2 months for those with a mean urine pH of 6.5 to 7.5, and 8.0 months for those with a mean urine pH of less than 6.5, which suggests a trend of a longer OS in patients with a higher urine pH (p = 0.0639). Alkalization therapy may offer a viable approach to extending the survival of stage 4 pancreatic cancer patients, who typically have an unfavorable prognosis.

Citric Acid Administration Protects Against Insulin-Induced Hypoglycemic Brain and Liver Injury

We aimed to investigate the effect of treatment with citric acid on oxidative stress and tissue injury in brain and liver of rats subjected to hypoglycaemia. Rats received intraperitoneal injections of insulin (5 IU/kg) followed 30 min later by oral administration of saline or citric acid at doses of 0.2, 0.4 or 1 g/kg. Rats were euthanized 1 h after insulin injection and their brains and livers were dissected out for biochemical studies including determination of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), paraoxonase-1 (PON-1), 5-lipoxygenase, and cholinesterase. Serum alanine aminotransferase and aspartate aminotransferase were determined and histological investigations for the liver were carried out. Results indicated that in insulin only treated rats, MDA and NO levels were significantly increased whereas GSH content and PON-1 activity significantly decreased in brain and liver tissue. In addition, cholinesterase activity significantly decreased while 5-lipoxygenase increased in brain with respect to the saline control group after insulin injection. Serum aminotransferases showed significant elevation in insulin-treated rats together with distorted hepatic architecture, hydropic degeneration, and extensive cytoplasmic vacuolation of hepatocytes. The biochemical alterations in the brain and liver of hypoglycaemic rats were markedly alleviated in a dose-dependant manner by the administration of citric acid which also markedly reduced the histological liver injury with the group treated with insulin and citric acid at 1 g/kg exhibiting more or less preserved hepatic architecture. These results indicate that citric acid was effective in alleviating the biochemical alterations in brain and liver and protecting against liver injury during hypoglycaemia. It could thus prove of benefit in patients on insulin therapy with accidental hypoglycaemia from over dosing.

Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats

Recent studies have reported that plasma levels of tricarboxylic acid (TCA) cycle metabolites and TCA cycle-related metabolite change in patients with chronic fatigue syndrome (CFS) and in healthy humans after exercise. Exogenous dietary citric acid has been reported to alleviate fatigue during daily activities and after exercise. However, it is unknown whether dietary citric acid affects the plasma levels of these metabolites. Therefore, the present study aimed to investigate the effects of exogenously administered citric acid on TCA cycle metabolites and TCA cycle-related metabolites in plasma. Sprague-Dawley rats were divided into control and citric acid groups. We evaluated the effect of exogenous dietary citric acid on the plasma TCA cycle and TCA cycle-related metabolites by metabolome analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). TCA cycle metabolites, including plasma citrate, cis-aconitate, and isocitrate, were significantly elevated after exogenous administration of citric acid. Anaplerotic amino acids, which are converted to TCA cycle metabolites, such as serine, glycine, tryptophan, lysine, leucine, histidine, glutamine, arginine, isoleucine, methionine, valine, and phenylalanine, also showed significantly elevated levels. Citric acid administration significantly increased the levels of initial TCA cycle metabolites in the plasma. This increase after administration of citric acid was shown to be opposite to the metabolic changes observed in patients with CFS. These results contribute novel insight into the fatigue alleviation mechanism of citric acid.

Soya milk alleviates toxicity caused by citric acid in male mice: Histopathological and hematological studies.

This study evaluated the toxicity of citric acid and the benefits of soya milk (SM) for preventing damage in mice. Thirty-five mice were divided into groups: control, mice administered citric acid (CA group) for 30days, mice administered SM before the administration of citric acid for 30days (SM+CA group), mice administered citric acid for 15days and left for recovery (R group), and mice in recovery receiving SM for 15days (R+SM). Mice in CA and R groups displayed downregulated p53, increased cleavage of caspase 3, and upregulation of Nrf2, CYP1A1, ALT, and AST activity in the liver. In contrast, SM+CA and R+SM treated mice were protected against CA toxicity and showed reversal of p53 downregulation, reduced cleavage of caspase 3, downregulation of Nrf2, and an increase in liver function enzymes. SM administration also restored blood cell and hemoglobin content and general histology of hepatocytes. PRACTICAL APPLICATIONS: CA causes liver damage, increases inflammation, decreases blood cell numbers, and induces apoptosis. Some natural products, such as SM, have been used to scavenge free radicals that can cause liver damage and hemolysis. This study focuses on the effectiveness of SM in ameliorating CA toxicity and may be helpful in the food industry for managing oxidative stress that may be induced by common dietary constituents. SM may help suppress liver damage and inflammation.

THE EFFECT OF CITRATE ACID ON THE PRODUCTION PERFORMANCE OF THE QUAIL (Coturnix coturnix japonica)

This study was aimed to determine the effect of citric acid on layer quail (Coturnix coturnix japonica) of production performance. The material used in this study was 80 quail of layer period (12 weeks) observed kept for five weeks. This study was used to complete randomized design with four treatments and five replications. Levels of citric acid administration were 0%, 0,3%, 0,6% and 0,9%, respectively. Parameters observed were feed consumption, egg production, egg weight, and feed conversion. The results showed that citric acid did not have a significant effect (P> 0,05) on feed consumption and quail egg weight, but gave real effect (P<0,05) to quail egg production and gave very significant effect (P<0,01) to feed conversion of quail. The addition of citric acid with a level of 0,6% (P2) gives better egg production and feed conversion than other treatments. Keywords: Quail, Citric Acid, Production Performance

Citric Acid Protects Dopaminergic Cells against Rotenone-Induced Neurodegeneration

We investigated the effect of citric acid on rotenone-induced oxidative stress and neuro- and hepato-toxicity. Swiss mice received subcutaneous injections of rotenone at a dose of 1.5 mg/kg once every other day for two weeks either alone or in combination with citric acid at 200 or 400 mg/kg given orally. The control group was treated with the vehicle dimethyl sulfoxide. The brain and liver levels of the lipid peroxidation product malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), and paraoxonase-1 (PON-1) activity were measured and as well as brain striatal concentrations of nuclear factor-kappa B (NF-kB) and tyrosine hydroxylase. Histopathology of the brain and liver tissue was also performed. Results indicated that MDA and NO content were increased whereas TAC and PON-1 decreased in the brain and liver tissue following rotenone injection. There was also increased NF-kB and decreased tyrosine hydroxylase concentrations in the brain of rotenone-treated mice. Rotenone-treated mice showed decreased striatal cell size and pyknotic nuclei. There were also interstitial hemorrhage and focal inflammatory cells infiltration in cerebral cortex, and degenerated neurons in cortex and hippocampus. The liver exhibited inflammatory cell infiltration and fibrosis. The administration of citric acid protected against rotenone-induced histopathological changes, decreased MDA, NO, and increased TAC and PON-1 activity in the brain and liver. It also reduced NF-kB and increased tyrosine hydroxylase in the brain of rotenone-treated mice. These data indicate that citric acid prevents rotenone-induced neuronal and liver damage via a decrease in oxidative stress. These findings suggest that supplementation with citric acid could be of value in the prevention of neuronal cell death in Parkinson’s disease.

Citrate therapy for calcium phosphate stones.

Calcium phosphate (CaP) stones represent an increasingly encountered form of recurrent nephrolithiasis, but current prophylactic medical regimens are suboptimal. Although hypocitraturia is a well-described risk factor for CaP stones, strategies that enhance citrate excretion have not consistently been effective at reducing CaP saturation and stone recurrence. This review summarizes the role of citrate therapy in CaP nephrolithiasis. Citrate in urine inhibits CaP stone formation through multiple mechanisms, including the formation of soluble citrate-calcium complexes, and inhibition of CaP nucleation, crystal growth and crystal aggregation. Recent in-vitro studies demonstrate that citrate delays CaP crystal growth through distinct inhibitory mechanisms that depend on supersaturation and citrate concentration. The impact of pharmacological provision of citrate on CaP saturation depends on the accompanying cation: Potassium citrate imparts a significant alkali load that enhances citraturia and reduces calciuria, but could worsen urine pH elevation. Conversely, citric acid administration results in minimal citraturia and alteration in CaP saturation. Citrate, starting at very low urinary concentrations, can significantly retard CaP crystal growth in vitro through diverse mechanisms. Clinically, the net impact on CaP stone formation of providing an alkali load during pharmacological delivery of citrate into the urinary environment remains to be determined.

Expression of Genes Related to Glycolysis in the Liver and Skeletal Muscle of Rats after Citric Acid Administration

Citric acid is known to alleviate physical fatigue and improve athletic performance; however, the underlying mechanism is unknown. Therefore, we aimed to investigate the effect of citric acid administration on the expression of key glycolysis-related genes in the liver and skeletal muscle of rats. Eight-week-old male Sprague-Dawley rats were divided into two groups—control and citric acid groups. The rats were fasted overnight, after which distilled water or citric acid solution was administered intragastrically; after 150 min, the rats were sacrificed, and the liver and skeletal muscle were collected. In the skeletal muscle, namely soleus and gastrocnemius muscles, the phosphofructokinase and pyruvate kinase gene expression were significantly decreased by citric acid administration. In contrast, the glucokinase and pyruvate kinase gene expression in the liver was significantly increased. These results suggest that exogenous dietary citric acid suppresses glycolysis in the skeletal muscle at the transcription level.

Productive performance, gut morphometry, and nutrient digestibility of broiler chicken in response to low and high dietary levels of citric acid

Summary Two experiments were conducted to evaluate the effects of dietary citric acid (CA) on productive performance, gut morphometry, and nutrient digestibility in broiler chickens. In Experiment 1, 200 7-day-old male Ross 308 broiler chicks were used to examine the effects of 0, 10, 20, and 30 g/kg CA up to day 42 of age in 5 replicates of 10 birds each. In Experiment 2, 90 7-day-old male Ross 308 broiler chicks were used to investigate the effects of 0, 30, and 60 g of CA per kg of diet in 3 replicate of 10 birds each up to day 42 of age. In both experiments, inclusion of 30 g/kg of CA increased proventriculus, gizzard, and ileum weight percentage and villus length, crypt depth, and goblet cell number in the duodenum, jejunum, and ileum compared to control birds. Ileal digestibility of crude protein (CP), apparent metabolizable energy (AME), and total phosphorus (tP) were improved. In Experiment 2, administration of CA at 60 g/kg of the diet significantly reduced ileal digestibility of CP, AME, and tP at 30 d of age (P

Acidic stress caused by dietary administration of citric acid in broiler chickens

Abstract. Citric acid (CA) is commonly used in poultry diets to promote growth by acidifying the gastrointestinal contents, improving nutrient digestibility, and reducing pathogen loads; therefore, this study was conducted to demonstrate the effects of 0, 30 and 60 g of CA per kilogramme of diet on productive performance, selected blood metabolites, immune response and certain gut-related variables in broiler chickens using 150, 7-day-old Ross 308 male broiler chicks in five replicates of 10 birds each per diet. Growth performance, daily feed intake and tibia phosphorous (P) retention were significantly improved by the diets containing 30 g kg−1 of CA (P < 0.01) but were suppressed as CA increased to 60 g kg−1. Dietary CA increased proventriculus, gizzard and ileum percentage and villus length, crypt depth and goblet cell number in duodenum, jejunum and ileum as well as ileal digestibility of crude protein, apparent metabolisable energy and total phosphorus while it decreased the pH of contents in the gut segments concerned (P < 0.01). Diets containing 60 g kg−1 of CA significantly reduced plasma P and Fe levels as well as cholesterol level and Alkaline phosphatase activity (P < 0.05) while increasing the aspartate aminotransferase and lactate dehydrogenase activities (P < 0.01) in the blood serum of the birds at day 42 of age. The percentage of bursa and thymus was greater in the birds fed on diets containing 60 and 30 g kg−1 of CA, respectively (P < 0.01). It was concluded that inclusion of 60 g kg−1 of CA in the diet resulted in a severe reduction in performance, nutrient digestion and absorption and liver dysfunctions in broiler chickens, a phenomenon we call as acidic stress.

Study of antagonism of citric acid on aluminum-induced toxicity in mice testis cells

To study the qualitative changes in testis tissue after aluminum chloride (AlCl3) administration and to determine whether citric acid (CA) has a protective effect against testis damage induced by AlCl3. In this study, 80 Kunming white mice were randomly separated into eight groups: (1) control, (2) CA (120 mg/kg), (3, 4 and 5) AlCl3 (20, 40 and 60 mg/kg), (6, 7 and 8) AlCl3 (20, 40 and 60 mg/kg) plus CA (120 mg/kg). After animals were killed, all testes were histopathologically examined under light microscopy; T-SOD and GSH-Px activities, H2O2 and MDA contents, and Bax and Bcl-2 levels were detected with the corresponding assay kits; DNA fragmentation were electrophoretically examined. Histopathological results indicated that AlCl3 severely damage to mouse testis tissues, however, the protective effects on testes was observed when AlCl3 combined with CA. Biochemical examination suggested that T-SOD and GSH-Px activities significantly decreased (P<0.05) in AlCl3 groups, while remarkably improved in CA+AlCl3 (especially middle and high dose groups) groups; H2O2 and MDA levels in higher-dose AlCl3 groups were obviously higher (P<0.05) than in CA+ corresponding dose AlCl3 groups. Cell apoptosis assays showed that Bax/Bcl-2 ratio in higher-dose AlCl3 groups were higher than CA+ higher-dose AlCl3 groups; and DNA fragmentation in middle-dose AlCl3 groups was much more apparent in CA+ middle-dose AlCl3 groups. It can be concluded that a certain concentration of AlCl3 exerts a reproductive toxicity to mice, and administration of citric acid can reduce the adverse effects of AlCl3 on testis.

Effects of the food additive, citric acid, on kidney cells of mice

Citric acid is a food additive that is widely used in the food and drink industry. We investigated the effects of citric acid injection on mouse kidney. Forty healthy mice were divided into four groups of 10 including one control group and three citric acid-treated groups. Low dose, middle dose and high dose groups were given doses of 120, 240 and 480 mg/kg of citric acid, respectively. On day 7, kidney tissues were collected for histological, biochemical and molecular biological examination. We observed shrinkage of glomeruli, widened urinary spaces and capillary congestion, narrowing of the tubule lumen, edema and cytoplasmic vacuolated tubule cells, and appearance of pyknotic nuclei. The relation between histopathological changes and citric acid was dose dependent. Compared to the control, T-SOD and GSH-Px activities in the treated groups decreased with increasing doses of citric acid, NOS activity tended to increase, and H2O2 and MDA contents gradually decreased, but the differences between any treated group and the control were not statistically significant. The apoptosis assay showed a dose-dependent increase of caspase-3 activity after administering citrate that was statistically significant. DNA ladder formation occurred after treatment with any dose of citric acid. We concluded that administration of citric acid may cause renal toxicity in mice.

Citric Acid Effects on Brain and Liver Oxidative Stress in Lipopolysaccharide-Treated Mice

Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-α) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-α, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

Effects of Dietary Citric Acid on Metabolic Indicators and Gene Expression in the Skeletal Muscles of Fasted Mice

Citric acid is recognized and utilized as a dietary supplement for its ability to eliminate fatigue. However, the molecular and cellular mechanism underlying this effect has not been elucidated. This study investigated the effect of intragastric citric acid administration on the energy metabolism and gene expression in the skeletal muscles of mice that had been fasted without exercise, using biochemical analyses of metabolic indicators and DNA microarrays. Expression of the genes involved in the glycolysis, tricarboxylic acid cycle and β-oxidation of fatty acids were not affected by citric acid administration. However, citric acid increased the level of blood glucose and expression of the phosphoenolpyruvate carboxykinase gene. These results indicate that citric acid ingestion may eliminate fatigue by promoting gluconeogenesis.

Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type 1) diabetic rats

Although many fruits such as lemon and orange contain citric acid, little is known about beneficial effects of citric acid on health. Here we measured the effect of citric acid on the pathogenesis of diabetic complications in streptozotocin-induced diabetic rats. Although oral administration of citric acid to diabetic rats did not affect blood glucose concentration, it delayed the development of cataracts, inhibited accumulation of advanced glycation end-products (AGEs) such as Nε-(carboxyethyl)lysine (CEL) and Nε-(carboxymethyl)lysine (CML) in lens proteins, and protected against albuminuria and ketosis. We also show that incubation of protein with acetol, a metabolite formed from acetone by acetone monooxygenase, generate CEL, suggesting that inhibition of ketosis by citric acid may lead to the decrease in CEL in lens proteins. These results demonstrate that the oral administration of citric acid ameliorates ketosis and protects against the development of diabetic complications in an animal model of type 1 diabetes.

Performance of acidified 14C‐urea capsule breath test during pantoprazole and ranitidine treatment

Urea breath test (UBT) results could be false negative in patients taking antisecretory drugs. This effect would be prevented by citric acid administration during UBT. We prospectively investigated whether acidified 14C-urea capsule prevents false negative UBT results in patients taking antisecretory drugs and show interference with the duration of medications. Sixty Helicobacter pylori positive patients were included. Pantoprazole (40 mg/day) was given to 27 patients for 28 days and ranitidine (300 mg. o.d.) to 33 patients for 60 days. Urea breath tests were repeated on days 14 and 28 in both groups and on day 60 in the ranitidine group. The baseline mean breath counts of two groups did not show any significant difference. Pantoprazole led to a significant decrease in mean breath counts on day 14 (P < 0.005). Six of 27 and 3 of 25 patients taking pantoprazole developed negative or equivocal UBT results on days 14 and 28, respectively. Two of 32, 2 of 32 and 3 of 21 patients taking ranitidine developed negative or equivocal UBT results on days 14, 28 and 60, respectively. The use of acidified 14C-urea capsule did not prevent false negative UBT results in patients taking pantoprazole and ranitidine, and the duration of medication does not affect the test results.

Effects of citric acid administration on femoral trabecular structures in ovariectomized mice

To examine the effects of citric acid administration on trabecular structures. Ovariectomized female ICR mice (n = 39), 8 weeks of age, were divided into four groups: ovariectomized control (OVX-control, n = 9, standard diet); citric acid (CIT, n = 10, citric acid 5 g/100 g diet); vitamin K2 (menaquinone 7; VK2, n = 10, vitamin K2 50 µg/100 g diet); and citric acid + vitamin K2 (CIT + VK2, n = 10, citric acid 5 g/100 g diet and vitamin K2 50 µg/100 g diet). After 12 weeks, the bone mass of the right femur was measured using peripheral quantitative computed tomography and the three-dimensional (3-D) trabecular structure of the right femur was assessed using microfocus computed tomography. The bone mineral density was significantly increased in the VK2 group versus the OVX-control group (P < 0.05). In the 3-D trabecular structure analysis, skeletal perimeter and number were significantly greater in the CIT, VK2, and CIT + VK2 groups than in the OVX-control group. Skeletal separation, spacing, and trabecular bone pattern factor were significantly lower in the CIT, VK2, and CIT + VK2 groups than in the OVX-control group. Almost all parameters in node–strut analysis were significantly greater in the CIT, VK2, and CIT + VK2 groups than in the OVX-control group. These results suggest that citric acid improved trabecular structures. However, simultaneous administration of citric acid and vitamin K2 did not have any additional effect.

Mechanisms of Capsaicin- and Citric-Acid-Induced Cough Reflexes in Guinea Pigs

Previously, we developed a novel coughing model that evoked coughs via citric acid microinjection into the larynx of unanesthetized, unrestrained guinea pigs. Here, we compared the effects of capsaicin and citric acid administration into the larynx using this model. Inhalation of capsaicin (30 µM) or citric acid (0.4 M) for 5 min induced cough mimetic responses over a 10-min observation period (mean ± S.E.M.: 8.85 ± 1.60 and 10.40 ± 1.17 coughs, respectively, n = 18). Microinjection of 0.4 M citric acid into the larynx (20 µl in total in 10 aliquots of 2 µl at 30-s intervals) induced 27.29 ± 2.69 coughs over a 10-min observation period, whereas microinjection of 3 mM capsaicin evoked a maximum of 8.32 ± 1.82 coughs (n = 18). Desensitization of C-fibers by capsaicin (100 mg/kg, s.c.) abolished the coughs evoked upon inhalation or microinjection of capsaicin and inhalation of citric acid, but had no significant effect on those induced by microinjection of citric acid. These results indicate that there were fewer nonmyelinated C-fiber afferents in the larynx area than in other regions (bronchi or alveoli). Consequently, citric acid microinjected into the larynx may induce the cough reflex by stimulating other fibers (for example, Aδ-fibers), rather than C-fibers. In contrast, inhaled citric acid predominantly stimulated C-fibers, and hardly affected Aδ-fibers.

Aluminum-induced oxidative stress in rat brain: response to combined administration of citric acid and HEDTA

Aluminum, a known neurotoxic substance, has been suggested as a contributing factor in the pathogenesis of Alzheimer's disease. Therapeutic efficacy of combined administration of citric acid (CA) and N-(2-hydroxyethyl) ethylenediaminetriacetic acid (HEDTA) was evaluated in decreasing blood and brain aluminum concentration and parameters indicative of hematological disorders and brain oxidative stress. Adult male wistar rats were exposed to drinking water containing 0.2% aluminum nitrate for 8 months and treated once daily for 5 consecutive days with CA (50 mg/kg, orally) or HEDTA (50 mg/kg, intraperitoneally) either individually or in combination. Aluminum exposure significantly inhibited blood δ-aminolevulinic acid dehydratase while increased zinc protoporphyrin confirming changed heme biosynthesis. Significant decrease in the level of glutathione S-transferase in various brain regions and an increase in whole brain thiobarbituric acid reactive substance, and oxidized glutathione (GSSG) levels were also observed. Glutathione peroxidase activity showed a significant increase in cerebellum of aluminum exposed rats. Most of the above parameters responded moderately to the individual treatment with CA and HEDTA, but significantly reduced blood and brain aluminum burden. However, more pronounced beneficial effects on some of the above described parameters were observed when CA and HEDTA were administered concomitantly. Blood and brain aluminum concentration however, showed no further decline on combined treatment over the individual effect with HEDTA or CA. We conclude that in order to achieve an optimum effect of chelation, combined administration of CA and HEDTA might be preferred. However, further work is needed before a final recommendation could be made.

Uptake index and stimulated salivary gland response in 99Tcm-pertechnetate salivary gland scintigraphy in normal subjects.

With a view to improve the diagnosis of salivary gland diseases (in particular, Sjögrén's syndrome) associated with decreased salivary gland function and decreased stimulated salivary gland response, the normal range of radionuclide uptake function and the stimulated salivary gland response were established in 27 subjects without any known salivary gland disease. Following injection of 99Tcm-pertechnetate, sequential images were recorded for 40 min with oral administration of citric acid at 30 min. The total uptake index (TUI) was calculated as the sum of the background corrected count rates over the parotid and submandibular glands at 3 min divided by the injected dose. The TUI, expressed as a percentage of dose, was 0.55 +/- 0.12 (mean +/- S.D.). The stimulated salivary gland response (SSGR) was calculated as the difference between the rate constants (min-1) of monoexponential fits to the time-activity curves over the four salivary glands immediately after and before the administration of citric acid. The lower significance limit (P < 0.05) of the SSGR was a 2.4% decrease per min. The parameters TUI and SSGR can be used as a diagnostic tool in, for example, early Sjögren's syndrome.