[Modified Premedication of Infusion Reaction with Obinutuzumab Therapy].

Obinutuzumab frequently triggers an infusion reaction(IR). In the GALLIUM study, despite the use of corticosteroids, antipyretic analgesics, and antihistamines to prevent IR, IR occurred at a high frequency of 68.2% for all Grades and 12.4% for Grades 3 or higher. The dose of methylprednisolone was increased from 80 mg administered in the GALLIUM study to 125 mg, and the development of IR was investigated in 30 patients with follicular lymphoma who received the initial dose of obinutuzumab. The incidence of IR was 43.3% for all Grades and 0% for Grades 3 or higher, and no serious IR was observed. It also had no effect on infectious diseases. Increased doses of corticosteroids were well tolerated and suggested as an effective method for reducing the frequency of IR.

Effect of the third dose of BNT162b2 COVID-19 mRNA vaccine on anti-SARS-CoV-2 antibody levels in healthcare workers.

PURPOSE: Administration of three doses of Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine was completed in Japan in the spring of 2022. This study aimed to evaluate the antibody responses, and kinetics of three doses of vaccine in healthcare workers (HCWs). PATIENTS AND METHODS: We conducted a longitudinal cohort study with HCWs, who had no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, from a single hospital. Immunoglobulin G (IgG) titers of anti-SARS-CoV-2 spike protein (SP) and nucleocapsid protein (NP) titers were measured using an automated chemiluminescent enzyme immunoassay system. RESULTS: A total of 636 HCWs participated in the study. The anti-SP IgG titers decreased slowly after the second dose of the BNT162b2 vaccine in all participants, and robust antibody response was observed after the third dose of the vaccine. The peak anti-SP IgG titer after the third dose was approximately 4.1-fold higher than that after the first and second doses, and the rate of decrease in the anti-SP IgG titer after the third dose was significantly more gradual, than that after the second dose. After the second dose of vaccine, the antibody response was weaker in older participants than in younger participants, and in males than in females respectively, whereas the response to the third dose of vaccine did not differ significantly by sex or age. Adverse events following immunization were generally mild to moderate. CONCLUSION: The third dose of the BNT162b2 vaccine induced a significant and sustained increase in anti-SP IgG titers, and was generally safe and well-tolerated.

Influence of analysis conditions for antimicrobial susceptibility test data on susceptibility rates.

BACKGROUND: To support effective antibiotic selection in empirical treatments, infection control interventions, and antimicrobial resistance containment strategies, many medical institutions collect antimicrobial susceptibility test data conducted at their facilities to prepare cumulative antibiograms. AIM: To evaluate how the setpoints of duplicate isolate removal period and data collection period affect the calculated susceptibility rates in antibiograms. METHODS: The Sakai City Medical Center is a regional core hospital for tertiary emergency medical care with 480 beds for general clinical care. In this study, all the Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae isolates collected at the Sakai City Medical Center Clinical Laboratory between July 2013 and December 2018 were subjected to antimicrobial susceptibility tests and the resulting data was analyzed. FINDINGS: The longer the duplicate isolate removal period, the fewer the isolates are available for every bacterial species. Differences in the length of the duplicate isolate removal period affected P. aeruginosa susceptibility rates to ß-lactam antibiotics by up to 10.8%. The setpoint of the data collection period affected the antimicrobial susceptibility rates by up to 7.3%. We found that a significant change in susceptibility could be missed depending on the setting of the data collection period, in preparing antibiogram of ß-lactam antibiotics for P. aeruginosa. CONCLUSIONS: When referring to antibiograms, medical professionals involved in infectious disease treatment should be aware that the parameter values, such as the duplicate isolate removal period and the data collection period, affect P. aeruginosa susceptibility rates especially to ß-lactam antibiotics. And antibiogram should be updated within the shortest time period that is practically possible, taking into account restrictions such as numbers of specimen.

Drug-induced lung disease adverse effect with Ledipasvir Acetonate/Sofosbuvir.

BACKGROUND: Interferon and ribavirin have been used as therapeutic agents for chronic hepatitis C infection or C-compensated cirrhosis in the conventional treatment. Hepatitis C virus (HCV) -specific direct-acting antiviral agents that directly inhibit the growth process of HCV have been approved since 2011. However, in the early post-marketing vigilance phase of ledipasvir acetonate/sofosbuvir (LDV/SOF), there were reports of interstitial lung disease in 4 out of 32,700 cases with death in 1 case; the onset mechanism is unknown. CASE PRESENTATION: Treatment for hepatitis C was deemed to be necessary, and the patient was referred to our hospital. Oral administration of LDV/SOF was started. On day 8 of administration, a fever of 38-39 °C and coughing were observed followed by the gradual appearance of shortness of breath. As there was no improvement, the patient visited her primary care physician on day 16 of administration and the patient was brought urgently to our hospital on the same day. Blood tests and imaging tests were conducted at our hospital on the day of emergency transport; inflammatory response markers showed abnormal values, and sialylated carbohydrate antigen Krebs von den Lungen-6 was within the normal value range at 303 U/mL. Because the possibility of infection was low based on results of imaging and bronchoalveolar lavage, drug-induced lung disease was suspected, LDV/SOF administration was discontinued, and steroid administration was started. Following steroid pulse therapy, treatment with oral prednisolone tablets was gradually tapered. The patient's symptoms were relieved and she was discharged. CONCLUSIONS: The patient's medication history in this case indicated that there were no drugs taken before or after administration of LDV/SOF until the adverse reaction occurred, and there were no supplements or dietary supplements taken. Therefore, LDV/SOF has been proposed as the cause of the suspected adverse effect. Pharmacists should try to collect adverse effect reports to identify adverse effects early.

Effects of semi-solidification of enteral nutrients on the pharmacokinetic behavior of orally administered carbamazepine in rats.

The use of semi-solid enteral nutrients plays an extremely important role in accurate nutrition management. In the present study, we compared the pharmacokinetic profile of orally administered carbamazepine (CBZ) in rats treated with liquid RACOL®, semi-solid RACOL®, and HINE E-gel®, which are enteral nutrients marketed in Japan. Since liquid and semi-solid formulations are both marketed in Japan for RACOL®, liquid RACOL® was orally administered to control rats. The serum concentration of CBZ at each sampling point was lower in the semi-solid RACOL®-treated group than in the liquid RACOL®-treated group. No significant differences were observed in the pharmacokinetic behavior of CBZ between the semi-solid RACOL®-treated and HINE E-gel®-treated groups. Regarding pharmacokinetic parameters, the impact of the area under the curve (AUC0→5h) was the liquid RACOL® group > the semi-solid RACOL® group ≈ the HINE E-gel® group. Therefore, we concluded that serum concentrations of CBZ were lower when concurrently treating with semi-solid enteral nutrients than when simultaneously processing liquid enteral nutrients.

Alterations in Pharmacokinetics of Orally Administered Carbamazepine in Rats Treated with Sodium alginate: Possible Interaction between Therapeutic Drugs and Semi-solid Enteral Nutrients.

OBJECTIVE: The use of enteral nutrients plays an extremely important role in accurate nutrition management. Sodium alginate (SA) is frequently used for the semi-solidification of enteral nutrients. In the present study, we investigated whether the pharmacokinetic profile of orally administered carbamazepine (CBZ) is altered by a treatment with SA immediately before and after dosing of the drug. Furthermore, the adsorption effects of SA on CBZ were examined using an in vitro analysis. METHOD: SA was orally administered to rats just before and immediately after CBZ dosing. The CBZ concentration profile following its oral administration was analyzed by a non-compartmental method. The adsorption of CBZ onto SA was evaluated after centrifugation using an ultrafiltration device. FINDINGS: The serum concentration of orally administered CBZ at each sampling point was reduced by the treatment with SA, and the extent of the decrease observed in the concentration of CBZ was larger when SA was ingested immediately after administration of the drug, which was consistent with the alteration observed in the value of the area under the curve (AUC). No significant differences were noted in the elimination rate at the terminal phase (ke) among the groups. In the in vitro assay, CBZ was adsorbed by SA in the solution used to reflect fluid in the intestinal tract. CONCLUSIONS: The pharmacological efficacies of CBZ might be reduced by SA through the pharmacokinetic interactions, and that the careful attention should be paid to the timing of administration of CBZ and semi-solid enteral nutrients.

Compatibility of Intravenous Fat Emulsion with Antibiotics for Secondary Piggyback Infusion.

BACKGROUND: The Guidelines for Parenteral and Enteral Nutrition in Japan state that parenteral fat emulsion can be infused through a secondary administration set. We tested the compatibility of fat emulsion with antibiotics in piggyback infusions in terms of changes in the size distribution of fat particles. METHODS: Test mixtures of 5% glucose solution, fat emulsion, and 25 antibiotic agents were prepared in the ratio appropriate for piggyback infusion (33: 10: 40) and analyzed serially for the number of fine particles by size using a light-shielded automatic fine particle counter. RESULTS: No marked changes were observed in the 12 ß-lactam antibacterial drugs, clindamycin phosphate, teicoplanin, trimethoprim/sulfamethoxazole, and micafungin sodium even at 24 h after preparation. The particle size in the mixture containing vancomycin hydrochloride, levofloxacin hydrate, metronidazole, and fluconazole gradually increased after preparation. The particle size in the mixture containing gentamicin sulfate, arbekacin sulfate, minocycline hydrochloride, ciprofloxacin, and fosfomycin sodium changed significantly after preparation. CONCLUSIONS: The changes in the particle size observed with some drugs suggest that they may cause changes in the lipid particle size during administration and, therefore, those antibiotics agents should not be administered concurrently with fat emulsion.

Bactericidal effects of deep ultraviolet light-emitting diode for solutions during intravenous infusion.

Background: Ultraviolet irradiation is effectively used as a disinfection method for inactivating microorganisms. Methods: We investigated the bactericidal effects by irradiation with a deep-ultraviolet light-emitting diode (DUV-LED) on the causative microorganisms of catheter related blood stream infection contaminating the solution for intravenous infusion. For irradiation, prototype modules for water disinfection with a DUV-LED were used. Experiments were conducted on five kinds of microorganisms. We examined the dependence of bactericidal action on eleven solutions. Administration sets were carried out three types. Results: When the administration set JY-PB343L containing the infusion tube made of polybutadiene was used, the bactericidal action of the DUV-LED against all tested microorganisms in the physiological saline solutions was considered to be effective. We confirmed that the number of viable bacteria decreased in 5% glucose solution and electrolyte infusions with DUV-LED irradiation. Conclusions: These results indicate that the DUV-LED irradiation has bactericidal effects in glucose infusion and electrolyte infusions by irradiating via a plasticizer-free polybutadiene administration set. We consider DUV-LED irradiation to be clinically applicable.

In vitro and in vivo effects of selected fibers on the pharmacokinetics of orally administered carbamazepine: Possible interaction between therapeutic drugs and semisolid enteral nutrients.

OBJECTIVE: The management of nutrition using semisolid enteral nutrients is considered useful for avoiding the adverse effects associated with liquid enteral nutrients. In the present study, we used an in vitro analysis to investigate whether carbamazepine (CBZ) is adsorbed by the fibers included in semisolid enteral nutrients. The effects of these fibers on the pharmacokinetic profile of CBZ following its oral administration were also examined in rats. METHODS: The adsorption of CBZ onto fibers was examined by absorbance monitoring of the filtrate after centrifugation using an ultrafiltration device. Viscosities of each solution were measured by rotational viscosimeter. The CBZ concentration profile after its oral administration (50 mg/kg) was analyzed by a noncompartmental method. RESULTS: In the two solutions used to reflect gastric juice and fluid in the intestinal tract, CBZ was more strongly adsorbed by water-soluble fibers (guar gum and xanthan gum) than by insoluble fibers (dextrin hydrate). The adsorption of CBZ also was observed even if the concentrations of guar gum and xanthan gum were reduced to such an extent that viscosity was 0 Paï½¥s. The pharmacokinetic examination of orally administered CBZ revealed that the area under the curve was significantly lower in the guar gum and xanthan gum groups than in the control group. CONCLUSION: CBZ was adsorbed by fibers used for the semisolidification of enteral nutrients, which may be partially responsible for the alterations observed in the pharmacokinetic profile of CBZ.

Water Soluble Vitamins Enhance the Growth of Microorganisms in Peripheral Parenteral Nutrition Solutions.

Peripheral parenteral nutrition (PPN) solutions contain amino acids, glucose, and electrolytes, with or without some water soluble vitamins. Peripheral venous catheters are one of the causes of catheter related blood stream infection (CRBSI), which requires infection control. In Japan, PPN solutions have rarely been prepared under aseptic conditions. However, in recent years, the necessity of adding vitamins to infusions has been reported. Therefore, we investigated the effects of water soluble vitamins on growth of microorganisms in PPN solutions. AMINOFLUID® (AF), BFLUID® (BF), PARESAFE® (PS) and PAREPLUS® (PP) PPN solutions were used. Water soluble vitamins contained in PP were also used. Causative microorganisms of CRBSI were used. Staphylococcus epidermidis decreased after 24 hours or 48 hours in all solutions. On the other hand, Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans increased, especially in PP. When each water soluble vitamin was added to BF and PS, growth of S. aureus was greater in solutions that contained nicotinamide than in solutions that contained other vitamins. As for C. albicans, they grew in all test solutions. C. albicans grew especially well in solutions that contained biotin. When commercial amino acids and glucose solutions with electrolytes are administered, in particular those containing multivitamins or water soluble vitamins, efforts to control infection must be taken to prevent proliferation of microorganisms.

[Effect of lidocaine gargling on taste perception].

Because stomatitis is a painful condition, gargling with lidocaine is often prescribed before meals. However, because lidocaine inhibits nerve conduction, lidocaine gargling may affect taste perception. Therefore, we studied the effects of lidocaine gargle on taste. We prepared samples of the 5 basic tastes at equivalent concentration levels in terms of the taste quotient. We conducted sensory tests to judge whether the samples could be tasted, and the threshold concentrations (50% taste rate) were estimated from the taste rates. The sensory test was repeated after the subjects gargled with lidocaine, and the efficacy ratio was calculated by comparing the threshold concentrations. Although no interaction was observed between the lidocaine gargle and the threshold concentration levels in the logistic regression analysis, significant differences were observed in the primary effects of each standard, such as the concentration levels, flavor, and bitterness. When the efficacy ratios based on the threshold values were calculated, increases in the thresholds for flavor and bitterness were observed. The results of this study suggested that gargling with lidocaine before a meal increases the thresholds for the appreciation of flavor and bitterness. This increase in the threshold values due to lidocaine was associated not with the pharmacological effect of the drug but with its strong bitterness.

Nitrogen-containing bisphosphonates inhibit RANKL- and M-CSF-induced osteoclast formation through the inhibition of ERK1/2 and Akt activation.

BACKGROUND: Bisphosphonates are an important class of antiresorptive drugs used in the treatment of metabolic bone diseases. Recent studies have shown that nitrogen-containing bisphosphonates induced apoptosis in rabbit osteoclasts and prevented prenylated small GTPase. However, whether bisphosphonates inhibit osteoclast formation has not been determined. In the present study, we investigated the inhibitory effect of minodronate and alendronate on the osteoclast formation and clarified the mechanism involved in a mouse macrophage-like cell lines C7 and RAW264.7. RESULTS: It was found that minodronate and alendronate inhibited the osteoclast formation of C7 cells induced by receptor activator of NF-κB ligand and macrophage colony stimulating factor, which are inhibited by the suppression of geranylgeranyl pyrophosphate (GGPP) biosynthesis. It was also found that minodronate and alendronate inhibited the osteoclast formation of RAW264.7 cells induced by receptor activator of NF-κB ligand. Furthermore, minodronate and alendornate decreased phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt; similarly, U0126, a mitogen protein kinase kinase 1/2 (MEK1/2) inhibitor, and LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, inhibited osteoclast formation. CONCLUSIONS: This indicates that minodronate and alendronate inhibit GGPP biosynthesis in the mevalonate pathway and then signal transduction in the MEK/ERK and PI3K/Akt pathways, thereby inhibiting osteoclast formation. These results suggest a novel effect of bisphosphonates that could be effective in the treatment of bone metabolic diseases, such as osteoporosis.

By inhibiting Src, verapamil and dasatinib overcome multidrug resistance via increased expression of Bim and decreased expressions of MDR1 and survivin in human multidrug-resistant myeloma cells.

The calcium channel blocker verapamil inhibits the transport function of multidrug resistance protein 1 (MDR1). Although verapamil acts to reverse MDR in cancer cells, the underlying mechanism remains unclear. In the present study, we investigated the mechanism of reversing MDR by verapamil in anti-cancer drug-resistant multiple myeloma (MM) cell lines. We found that verapamil suppresses MDR1 and survivin expressions and increases Bim expression via suppression of Src activation. Furthermore, dasatinib reversed the drug-resistance of the drug-resistant cell lines. These findings suggest that Src inhibitors are potentially useful as an anti-MDR agent for the treatment of malignant tumor cells.

Activation of NF-κB by the RANKL/RANK system up-regulates snail and twist expressions and induces epithelial-to-mesenchymal transition in mammary tumor cell lines.

BACKGROUND: Increased motility and invasiveness of cancer cells are reminiscent of the epithelial-mesenchymal transition (EMT), which occurs during cancer progression and metastasis. Recent studies have indicated the expression of receptor activator of nuclear factor-κB (RANK) in various solid tumors, including breast cancer. Although activation of the RANK ligand (RANKL)/RANK system promotes cell migration, metastasis, and anchorage-independent growth of tumor-initiating cells, it remains to be investigated if RANKL induces EMT in breast cancer cells. In this study, we investigated whether RANKL induces EMT in normal breast mammary epithelial cells and breast cancer cells, and the mechanism underlying such induction. METHODS: Expression levels of vimentin, N-cadherin, E-cadherin, Snail, Slug, and Twist were examined by real-time polymerase chain reaction. Cell migration and invasion were assessed using Boyden chamber and invasion assays, respectively. The effects of RANKL on signal transduction molecules were determined by western blot analyses. RESULTS: We found that stimulation by RANKL altered the cell morphology to the mesenchymal phenotype in normal breast epithelial and breast cancer cells. In addition, RANKL increased the expression levels of vimentin, N-cadherin, Snail, and Twist and decreased the expression of E-cadherin. We also found that RANKL activated nuclear factor-κB (NF-κB), but not extracellular signal-regulated kinase 1/2, Akt, mammalian target of rapamycin, c-Jun N-terminal kinase, and signal transducer and activator of transcription 3. Moreover, dimethyl fumarate, a NF-κB inhibitor, inhibited RANKL-induced EMT, cell migration, and invasion, and upregulated the expressions of Snail, Twist, vimentin, and N-cadherin. CONCLUSIONS: The results indicate that RANKL induces EMT by activating the NF-κB pathway and enhancing Snail and Twist expression. These findings suggest that the RANKL/RANK system promotes tumor cell migration, invasion, and metastasis via the induction of EMT.

Inhibition of the tumour necrosis factor-alpha autocrine loop enhances the sensitivity of multiple myeloma cells to anticancer drugs.

Several autocrine soluble factors, including macrophage inflammatory protein-1α and tumour necrosis factor-alpha (TNF-α), promote the survival and growth of multiple myeloma (MM) cells. We hypothesised that inhibition of the TNF-α autocrine loop may enhance the cytotoxic effect of anticancer drugs in MM cell lines. In the present study, a TNF-α-neutralizing antibody suppressed cell proliferation and enhanced the cytotoxic effect of anticancer drugs on MM cells. In addition, combination treatment with the TNF-α-neutralizing antibody and the chemotherapy agent melphalan inhibited nuclear factor κB (NF-κB) p65 nuclear translocation and mammalian target of rapamycin (mTOR) activation and upregulated the expression of Bax and Bim. Treatment of ARH-77 cells with the NF-κB inhibitor dimethyl fumarate or the mTOR inhibitor rapamycin suppressed NF-κB p65 nuclear translocation and enhanced the cytotoxic effect of melphalan. Furthermore, infliximab, a monoclonal antibody against TNF-α, also enhanced the cytotoxic effect of anticancer drugs in ARH-77 cells. These results indicated that TNF-α-neutralizing antibodies or infliximab enhanced the cytotoxic effect of anticancer drugs by suppressing the TNF receptor/mTOR/NF-κB pathways. The inhibition of TNF-α may thus provide a new therapeutic approach to control tumour progression and bone destruction in MM patients.

Nitrogen-containing bisphosphonates induce apoptosis of hematopoietic tumor cells via inhibition of Ras signaling pathways and Bim-mediated activation of the intrinsic apoptotic pathway.

Nitrogen-containing bisphosphonates (N-BPs) induce apoptosis in tumor cells by inhibiting the prenylation of small G-proteins. However, the details of the apoptosis-inducing mechanism remain obscure. The present study showed that the induction of apoptosis by N-BPs in hematopoietic tumor cells is mediated by mitochondrial apoptotic signaling pathways, which are activated by the suppression of geranylgeranyl pyrophosphate (GGPP) biosynthesis. Furthermore, N-BPs decreased the levels of phosphorylated extracellular signal-regulated kinase (ERK) and mTOR via suppression of Ras prenylation and enhanced Bim expression. The present results indicated that N-BPs induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, and enhancing Bim expression through inhibition of the Ras/MEK/ERK and Ras/mTOR pathways. The accumulation of N-BPs in bones suggests that they may act more effectively on tumors that have spread to bones or on Ras-variable tumors. This is the first study to show that the specific molecular pathways of N-BP-induced apoptosis.

[A case of interstitial lung diseases in patient treated with oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX)].

FOLFOX/bevacizumab has been shown to be a promising chemotherapeutic regimen for advanced or metastatic colorectral cancer. We reported a case of intestinal lung diseases occurring in association with the use of this combination chemotherapy. The patient presented here is a 71-year-old man with lung metastasis of rectal cancer who was treated with FOLFOX4/ bevacizumab. He complained of high fever in the eleventh course of a FOLFOX4/bevacizumab regimen. Chemotherapy was stopped. But fourteen days after, he suffered from dyspnea and soon went into respiratory failure of WHO grade 3 with severe hypoxemia. He was diagnosed with interstitial pneumonitis. Corticosteroid therapy consisting of metylprednisolone(1 g/day) for tree days was significantly effective in treatment of respiratory failure. Drug-induced interstitial pneumonitis was suspected from chest X-ray and CT. We performed DLST of oxaliplatin, l-levofolinate, 5-FU and bevacizumab for him. He was positive for oxaliplatin and l-levofolinate and 5-FU, and negative for bevacizumab. Interstitial pneumonitis induced by FOLFOX/bevacizumab chemotherapy is rare, but six patients had developed, one of whom died in post-marketing surveillance. The possibility of interstitial pneumonitis should always be considered when a patient presents with a respiratory disorder while undergoing systemic chemotherapy.

Quality of twelve clarithromycin dry syrup formulations-bitterness, grittiness and uniformity of drug loading.

The objective of the study was to evaluate the bitterness, grittiness and uniformity of drug loading as measures of the quality of 12 formulations of clarithromycin dry syrup (CAMDS), comprising one branded and 11 generic products. Some of the generic CAMDS formulations were more bitter than the branded product while others had similar bitterness when tested as aqueous suspensions. Only one generic product was less bitter than the branded product when tested as a suspension in acidic sports drink. The usual dissolution test described in JP XV could not be used to evaluate the bitterness of the products. A brief dissolution test using only 12.5 ml of water was used to evaluate the bitterness of the products in aqueous suspensions. There were considerable variances in the grittiness of the various products, which were independent of particle size. Changes in grittiness level seemed to be correlated with changes in the intensity of bitterness due to the disintegration of the formulation. Finally, there was less variation in the uniformity of drug loading for the branded product than for the generic products. These data may be useful when selecting which CAMDS formulation to prescribe.

Suppression of bitterness and improvement of palatability of commercial prednisolone powder.

The aim of the study was to suppress the bitterness and improve the palatability of pediatric prednisolone powder (PP) by the addition of simple sucrose syrup (SS) and various beverages and foods. Bitterness suppression was evaluated using the human gustatory sensory test. The suppression of the bitterness and improvement of palatability of PP by addition of SS solutions was investigated using standard taste substances: sucrose for sweetness, tartaric acid for sourness, and sodium chloride as saltiness. Dilution with SS solutions of up to 50% (w/w) was successful in bitterness-suppression and improvement of palatability, but at 80% (w/w) SS, the palatability of the diluted solution was reduced. The kinematic viscosities of SS solutions were therefore evaluated using the Uberorde viscosity meter, to see whether the high viscosity of the more concentrated solutions was responsible for the reduced palatability. The kinematic viscosity of the 80% SS was 16.60 mm(2)/s. Judging from above information, the palatability might become worse when the kinematic viscosity of syrup exceeded 15 mm(2)/s. Finally, the ability of various beverages and foods with low viscosity to suppress the bitterness and improve the palatability of PP were examined. The additions of orange juice or a carbonated lemon drink to simple syrup solution were most effective in suppressing bitterness and improving palatability of PP.

Inhibitory effect of aroma on the bitterness of branched-chain amino acid solutions.

Nutritional products for patients with liver failure available on the Japanese market contain many branched-chain amino acids (BCAAs) such as L-leucine, L-isoleucine, and L-valine, which not only have a bitter taste but also strong, unpleasant odours, leading to low palatability. The palatability of these nutritional products can be significantly improved by the addition of flavoured powders containing various kinds of tastants (sucrose, citric acid, etc.) and odourants (fruit, coffee aromas, etc.). The specific effects of the aroma of flavoured powders have not yet been clearly evaluated. In the present article, the inhibitory effect of aroma on the bitterness of BCAA solutions was examined. The bitterness intensity of a BCAA solution at the same concentration as Aminoleban EN was defined as 3.5 (measured by a previously described gustatory sensation method). The bitterness threshold of a BCAA standard solution without added aroma was estimated to be 1.87, while those of BCAA solutions containing green-tea, coffee, apple, vanilla, or strawberry aromas were 2.02, 1.98, 2.35, 2.40 and 2.87, respectively, when evaluated by the probit method. This shows that the addition of an aroma can elevate the bitterness threshold in human volunteers. The green-tea and coffee aromas predominantly evoked bitterness, while the vanilla aroma predominantly evoked sweetness. Apple and strawberry aromas evoked both sweetness and sourness, with the apple aroma having stronger sourness and the strawberry aroma stronger sweetness. Thus, a 'sweet' aroma suppresses the bitterness of BCAA, with coexisting sourness also participating in the bitterness inhibition.