Immunostimulatory effect of Antrodia camphorata extract on functional maturation of dendritic cells

Dendritic cells (DCs) are now recognised as the most potent professional antigen presenting cells (APCs) involved in initiating primary immune responses. The medicinal mushroom Antrodia camphorata (AC) is one of the most popular chemopreventive mushrooms in Taiwan. Polysaccharides of mushroom products are among emerging new agents that activate maturation and functions of DCs. The aim of this study is to investigate the immunomodulating activity of A. camphorata extract (ACW) on functional maturation of DCs. Compared with lipopolysaccharides (LPS), ACW effectively promoted the functional maturation of DCs in the expression of phenotypic characteristics and IL-12 production and chemotaxic activity. Moreover, ACW increased the phosphorylation of Akt, p38, and JNK/MAPKs in DCs. Specific inhibitors, SB203580 and LY94002, significantly blocked the ACW-induced up-regulation of costimulatory factor expression, IL-12 production. These findings suggest that ACW is a potent adjuvant for cancer immunotherapy and promotes Th1 immune responses.     

Antibacterial activities of Anisomeles indica constituents and their inhibition effect on Helicobacter pylori-induced inflammation in human gastric epithelial cells

The antibacterial activity of Anisomeles indica extract, and its isolated constituents against Helicobacter pylori growth were examined. Among tested, ethanol extract, pure constituents ovatodiolide (OVT) followed by acteoside, isoacteoside, and terniflorin showed potent antimicrobial activity. OVT demonstrated bactericide activity against H. pylori reference, as well as multidrug-resistant strains. On the other side, in vitroH. pylori-infection model revealed that OVT inhibited the H. pylori bacteria adhesion and invasion to human gastric epithelial (AGS) cells. In addition, OVT inhibited the H. pylori-induced inflammatory response by the reduced nuclear factor (NF)-κB activation and interleukin (IL)-8 expressions in H. pylori-infected AGS cells. Furthermore, OVT attenuated the cytotoxin-associated gene A (CagA) functions by reduced CagA translocation, phosphorylation, and caused hummingbird phenotype of AGS cells. These results indicate that OVT might be useful as food supplement or drug development for H. pylori complications.     

Evaluation of the effect of defrosting practices of ground beef on the heat tolerance of Listeria monocytogenes and Salmonella Enteritidis

The effect of common defrosting practices of ground beef, including (i) defrosting in the refrigerator (5 °C for 15 h), (ii) defrosting at room temperature (25 °C for 12 h) and (iii) defrosting in the microwave, on the heat tolerance of artificially inoculated Listeria monocytogenes and Salmonella Enteritidis, was studied. The thermal inactivation of S. Enteritidis was not, overall, affected by defrosting practices. In contrast, defrosting at room temperature resulted, overall, in an increased heat tolerance of L. monocytogenes compared to the rest tested defrosting practices. Inactivation kinetics of the two pathogens for the different defrosting practices were determined by fitting the data to the Weibull model. The δ parameter of the Weibull model (heat challenge time (min) required for the first 1-log reduction) for S. Enteritidis and for defrosting at 25 °C, microwave defrosting, defrosting at 5 °C and for the control (fresh ground beef inoculated with the pathogens just before the heat challenge trials) was 1.13, 1.62, 1.60 and 0.96, respectively, while the corresponding values for L. monocytogenes were 20.13, 10.82, 9.95 and 9.47, respectively. The findings of this study should be useful in risk assessments and in developing food handling guidelines for the consumers.     

Effect of Zataria multiflora Boiss. essential oil and nisin on Salmonella typhimurium and Staphylococcus aureus in a food model system and on the bacterial cell membranes

The effects of different concentrations of Zataria multiflora Boiss. essential oil (EO: 0, 5, 15 and 30 μl 100 ml⁻¹) and nisin (N: 0, 0.25 and 0.5 μg ml⁻¹), temperatures (T: 25 and 8 °C), and storage times (up to 21 days) on growth of Salmonella typhimurium and Staphylococcus aureus in a commercial barley soup were evaluated in a factorial design study. The growth of S. typhimurium was significantly (P < 0.05) decreased by EO concentrations and their combinations with N concentrations at 8 °C. For S. aureus, the viable count was significantly (P < 0.05) inhibited by EO and N concentrations and their combinations, incubated at both storage temperatures. The mechanism of the antimicrobial action of EO, N, and their combinations against cell membranes of the tested organisms were also studied by measurement of the release of cell constituents and by the electronic microscopy observations of the cells. The significant increase of the cell constituents’ release of both organisms was observed as a result of treatments with EO and EO in combination with N. Electronic microscopy observations revealed that the cell membranes of S. typhimurium treated by EO and EO in combination with N were significantly damaged, while cells treated with only N looked similar to untreated cells. The electron micrographs of treated cells of S. aureus with EO, N, and their combination also showed important morphological damages and disrupted membranes.     

Simulation of the effect of sausage ingredients and technology on the functionality of the bacteriocin-producing Lactobacillus sakei CTC 494 strain

Bacteriocin-producing lactic acid bacteria may be applied as novel functional starter cultures for sausage fermentation. In this way, safer and more standardised end products may be obtained. However, it is not clear how such strains behave under sausage fermentation conditions. In this study, the combined effects of typical sausage ingredients and process technology on the functionality of Lactobacillus sakei CTC 494 were simulated by a modelling approach. Under simulated sausage fermentation conditions, the strain was able to produce a considerable amount of bacteriocin. Model simulations indicate that sausage fermentation conditions of temperature and pH favour bacteriocin production, whereas salting and curing with sodium nitrite decrease growth and bacteriocin production. Sodium nitrite inhibits cell growth under its undissociated nitrous acid form, and its inhibitory effect seems to parallel lactic acid production. Whereas oxygen and magnesium levels did not influence bacterial functionality, manganese limitations severely decreased cell growth. Moreover, the presence of large amounts of fat, which is typical for a sausage environment, leads to an apparent bacteriocin inactivation, probably due to adsorption of the bacteriocin molecules from the water phase to the fat particles.     

The effect of nisin and garlic (Allium sativum L.) essential oil separately and in combination on the growth of Listeria monocytogenes

In the present study, the anti-listerial activity of the nisin and garlic (Allium sativum L.) essential oils (GO) alone and in combination was investigated at different temperatures (20 and 30 °C), pH (6.8, 5.6 and 4.8) and NaCl concentrations (0, 0.5, 2.5 and 4.5 g/100 mL). Minimum inhibitory concentrations (MICs) against Listeria monocytogenes were assessed for the nisin and essential oil. Furthermore, for combinations of the antimicrobials, the Differences in Population (DP) method were used to determine their effect. Both essential oil and nisin possessed considerable antimicrobial effects on the microorganism. The MICs for nisin and GO were 12.5 IU/mL and 100 μg/mL, respectively. Regardless of NaCl concentration and temperature, the anti-listerial activity of both GO and nisin was strongly influenced by pH. Moreover, at the same temperature, and regardless of pH value, the growth of the organism was also affected by increasing NaCl concentration. In combination, the DP was related strongly to the agent’s concentration and media pH. Meanwhile, among all combined systems, the effect of the combination (EC) of nisin with GO at 30 °C, pH 5.6 and 0 g/100 mL NaCl, showed significant anti-listerial activity (P ≤ 0.05).     

高压热杀菌处理时D-果糖对枯草芽孢杆菌芽孢灭活的抑制机制

研究高压热杀菌(high-pressure thermal sterilization, HPTS)处理时D-果糖对枯草芽孢杆菌芽孢灭活的抑制作用。HPTS处理压力为200、600MPa,处理温度为25、65、75℃,处理时间为 20min, D-果糖质量分数为0、15%、30%、60%。使用流式细胞术检测处理前后芽孢内膜的损伤情况,采用傅里叶红外光谱对处理前后芽孢蛋白质和内膜脂质进行分析,以揭示蛋白质结构与内膜脂质相态的变化。HPTS处理后芽孢内膜通透性增大,内膜完整性受损,然而随着添加的D-果糖质量分数的升高,芽孢内膜脂质的相态由液晶态逐渐转变为凝胶态,内膜稳定性增加、通透性降低、完整性提高,且芽孢蛋白质的有序二级结构的含量增加。不添加D-果糖时,600MPa、75℃处理20min后,芽孢死亡了5.31 lg(CFU/mL),芽孢悬浮液OD₆₀₀下降到0.41,2,6-吡啶二羧酸(2,6-pyridinedicarboxylic acid, DPA)泄漏率达93.56%,内膜受损的芽孢比率达到80.95%,芽孢蛋白质的α-螺旋和β-折叠结构含量分别下降到16%和17%;而当添加的D-果糖质量分数提升到60%时,相同条件的HPTS处理后,芽孢存活数量上升了1.69 lg(CFU/mL),芽孢悬浮液OD₆₀₀上升了0.09,内膜受损的芽孢比率减少了20.74个百分点,芽孢蛋白质的α-螺旋和β-折叠结构含量分别回升到25%和28%。D-果糖抑制了HPTS处理对芽孢结构的破坏和孢内关键物质的泄漏,且这种作用与D-果糖质量分数呈正相关。     

沙门氏菌检验用培养基的质量控制标准研究

目的 通过筛选沙门氏菌检验用培养基的质控菌株,为GB 4789.28—2013标准的修订和企业培养基的质控提供依据。方法 使用GB 4789.28中规定的菌株及从食品中分离的9株沙门氏菌,分别为纽波特沙门氏菌、婴儿沙门氏菌、猪霍乱沙门氏菌、布里丹沙门氏菌、科特布斯沙门氏菌、亚利桑那肠沙门氏菌、都柏林沙门氏菌、阿贡纳沙门氏菌和鸭沙门氏菌,通过定量和半定量方法测试10种不同品牌的RV肉汤、亚硒酸盐胱氨酸增菌液、四硫磺酸钠亮绿培养基和亚硫酸铋琼脂、HE琼脂、木糖赖氨酸脱氧胆盐分离培养基的生长率和选择性的差异,以评价市场现有培养基的质量差异及GB 4789.28—2013中所用的质控菌株是否能满足沙门氏菌培养基的质量控制。结果结果显示用同一株菌进行检测时,不同品牌的培养基的生长率和选择性存在差异,且猪霍乱沙门氏菌（Salmonella choleraesuis）和亚利桑那肠沙门氏菌（Salmonella arizona）对培养基的质量有更高的要求。结论 建议培养基生产企业及微生物实验室在培养基检验过程中,使用从食品中分离出的,对培养基质量要求高的质控菌株,同时质控方法应予以高度规范化,以保障检...     

超声辅助酶解对龙头鱼蛋白肽理化性质及风味特性的影响

目的:解决龙头鱼酶解蛋白肽鲜味低、苦味重、风味不良等问题。方法:利用超声辅助酶解法制备龙头鱼蛋白肽,以木瓜蛋白酶作为催化剂,研究不同超声功率(0,120,240,480,600 W)条件下龙头鱼蛋白肽粒径、水解度、可溶性多肽含量、相对分子质量分布、游离氨基酸含量以及电子舌风味信号的变化,进而探究不同超声强度对龙头鱼蛋白肽结构及风味特性的影响。结果:超声强度360 W、超声时间1 h,水浴温度55℃以及水浴时间4 h的条件下,蛋白质水解度达到19.29%,可溶性多肽含量为0.57 mg/mL,超声辅助显著降低了龙头鱼蛋白肽的粒径和相对分子质量,相对分子质量<3 000的组分占比从67%增加至82%。此外,龙头鱼蛋白肽中,苦味氨基酸占主要地位,其次是甜味和鲜味氨基酸。超声辅助酶解蛋白肽中鲜味游离氨基酸含量的增幅最大,因此,超声辅助酶解通过增加鲜味氨基酸的含量降低了龙头鱼蛋白肽的苦味。结论:超声辅助可以提高龙头鱼蛋白的酶解作用,进而改善龙头鱼多肽的理化性质及风味特性。     

Hepatoprotective effect of the root extract of Decalepis hamiltonii against carbon tetrachloride-induced oxidative stress in rats

Decalepis hamiltonii, a climbing shrub, grows in the forests of peninsular India and is consumed for its health promoting properties. The hepatoprotective activity of the aqueous extract of the roots of D. hamiltonii with known antioxidant constituents was studied against carbon tetrachloride (CCl₄)-induced oxidative stress and liver injury in rats. Pretreatment of rats with aqueous extract of the roots of D. hamiltonii, single (50, 100 and 200 mg/kg b.w.) and multiple doses (50 and 100 mg/kg b.w. for 7 days) significantly prevented the CCl₄ (1 ml/kg b.w.) induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, ALP, and LDH). Parallel to these changes, the root extract also prevented CCl₄-induced oxidative stress in the rat liver by inhibiting lipid peroxidation and protein carbonylation, and restoring the levels of antioxidant enzymes (SOD, CAT, GPx, GR, and GST) and glutathione. The biochemical changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the root extract in a dose dependent manner. Protective effect of the aqueous extract of the roots of D. hamiltonii against CCl₄-induced acute hepatotoxicity could be attributed to the antioxidant constituents.     

Protection of Lactobacillus acidophilus from the low pH of a model gastric juice by incorporation in a W/O/W emulsion

The protective effect of a W/O/W emulsion for Lactobacillus acidophilus from a model gastric juice was investigated in order to develop a method for utilizing the advantages of the probiotics. The bacteria were included in the inner-phase solution of the W/O/W emulsion, and a method for counting the viable-bacteria included in the W/O/W emulsion was developed. The relative viability of the bacteria included in the W/O/W emulsion was 49% at 2 h in the model gastric juice, whereas the viability of the bacteria directly dispersed in the juice declined to 1.3% even at 0.67 h. The relative viabilities of the encapsulated bacteria in the model gastric juice at 2 h were 0.12 and 1.10 for the emulsions having the median diameters of 11.9 and 25.4 μm, prepared with inner-phase volume ratios at 0.03 and 0.45, respectively. The relative viabilities of the bacteria in the W/O/W emulsions with the median diameters of 11 and 27 μm, prepared at the homogenization speed of 2.2×10⁴ and 9.8×10³ rpm, were 0.4 and 0.8, respectively. These results suggested that both the inner-phase volume ratio and the median diameter of oil droplet affected the relative viability of the included bacteria.     

Influence of Alyssum homolocarpum seed gum on the stability and flow properties of O/W emulsion prepared by high intensity ultrasound

This study introduces Alyssum homolocarpum seed gum, as a natural stabilizer for O/W emulsions. The droplets characteristics, flow properties and physical stability of ultrasonically prepared corn oil-in-water emulsions were investigated at various gum concentrations. The results indicated that for the freshly prepared emulsions, the mean diameter of droplets decreased significantly with an increase in gum concentration from 0.25% to 0.75%. Storage of emulsions for a period of 4 weeks resulted in an increase in the size of droplets, being substantially greater for the samples containing 0.25 and 0.5% gum and negligible for those prepared with 0.75 and 1.0% gum. Similar trend was observed for the specific surface area of droplets but in the opposite direction. Optical microscopy demonstrated that increasing the proportion of gum up to 0.75% reduced the extent of flocculation and coalescence and enhanced monodispersity. Newtonian and non-Newtonian shear-thinning flow behaviors were observed for emulsions prepared with 0.25% gum concentration and those containing higher concentrations respectively. Accordingly, faster creaming was found to be associated with the emulsions prepared with low gum concentration.     

基于蒸制处理的黄精麻味物质研究

目的：探索黄精产生麻味特征的物质基础。方法：采用“九蒸九制”的方法对8个产地的黄精进行炮制,并分析不同蒸制次数下黄精中皂苷、多酚、草酸钙针晶含量的变化;采用细胞溶血率试验以及感官评价方法评价黄精麻味程度的变化,并进行麻味相关性分析。结果：随着蒸制次数的增加,不同产地的黄精中多酚和皂苷含量均呈先升后降的趋势,而草酸钙针晶含量、细胞溶血率以及麻味评分均逐渐下降;相关性分析表明,草酸钙针晶含量与黄精麻感程度之间呈显著正相关（P＜0.05）或者极显著正相关（P＜0.01）;扫描电镜结果显示,蒸制处理后草酸钙针晶结构逐步遭到破坏,与黄精麻味的变化规律相吻合。结论：草酸钙针晶是黄精具有麻味特征的关键物质。     

Synergistic effect of Pulsed Electric Fields and CocoanOX 12% on the inactivation kinetics of Bacillus cereus in a mixed beverage of liquid whole egg and skim milk

With a view to extending the shelf-life and enhancing the safety of liquid whole egg/skim milk (LWE–SM) mixed beverages, a study was conducted with Bacillus cereus vegetative cells inoculated in skim milk (SM) and LWE–SM beverages, with or without antimicrobial cocoa powder. The beverages were treated with Pulsed Electric Field (PEF) technology and then stored at 5 °C for 15 days. The kinetic results were modeled with the Bigelow model, Weibull distribution function, modified Gompertz equation, and Log-logistic models.Maximum inactivation registered a reduction of around 3 log cycles at 40 kV/cm, 360 µs, 20 °C in both the SM and LWE–SM beverages. By contrast, in the beverages supplemented with the aforementioned antimicrobial compound, higher inactivation levels were obtained under the same treatment conditions, reaching a 3.30 log₁₀ cycle reduction.The model affording the best fit for all four beverages was the four-parameter Log-logistic model.After 15 days of storage, the antimicrobial compound lowered Bacillus cereus survival rates in the samples supplemented with CocoanOX 12% by a 4 log cycle reduction, as compared to the untreated samples without CocoanOX 12%. This could indicate that the PEF-antimicrobial combination has a synergistic effect on the bacterial cells under study, increasing their sensitivity to subsequent refrigerated storage.     

裸藻对戚风蛋糕品质及抗氧化能力的影响

目的:探索裸藻对戚风蛋糕品质的影响。方法:将裸藻粉添加到戚风蛋糕中,探索不同添加量(0.0%,2.0%,4.0%,6.0%,8.0%)对蛋糕比容、含水量、色泽、质构特性、感官评价及蛋糕抗氧化能力的影响。结果:添加裸藻粉后,蛋糕的比容和亮度降低,但其含水量变化不大。随着裸藻粉添加量的增加,蛋糕的硬度、胶着性和咀嚼性明显增大,弹性、回复性、内聚性变化不大。添加裸藻粉可以显著提高蛋糕的抗氧化能力,且抗氧化能力的提高与裸藻粉添加量具有极强的正相关性(P<0.01)。综合质构和感官分析,当裸藻粉添加量为4.0%时,感官评分最高,羟自由基清除率和总抗氧化能力分别比对照组提高了15.3%和17.0%。结论:在戚风蛋糕中添加裸藻粉,可以显著提高蛋糕的抗氧化能力和营养价值,还能一定程度上改善蛋糕的品质。     

Modelling the individual cell lag phase: effect of temperature and pH on the individual cell lag distribution of Listeria monocytogenes

The individual-based approach of the lag phase is gaining interest, especially for pathogens that initially contaminate food products in low amounts. In this paper, the effect of temperature (30, 10, 7, 4 and 2 °C) and pH (7.4, 6.1, 5.5, 5.0, 4.7 and 4.4) on the individual cell lag phase of Listeria monocytogenes was examined in a factorial design, using OD measurements. Individual lag phases of about 100 individual cells per condition were examined and calculated using a linear extrapolation method. Generation times were calculated out of the slope.The obtained data were analyzed at three different levels: in a first approach, the mean values were calculated for each set of environmental conditions and compared to predictions made by the USDA's Pathogen Modeling Program (PMP) for analogous growth conditions. The PMP predictions of the generation times were in the same order of magnitude as the obtained data, although a persistent underestimation could be observed. The observed individual cell lag data differed from lag phase predictions by PMP. Possible reasons for this discrepancy are discussed.Secondly, histograms of individual lag phase measurements were constructed for the different temperature–pH combinations. In this way, the influence of both factors on the variability of individual lag phases could be estimated. At low stress levels, most individual cells showed a short lag phase resulting in a compression of the histograms at the zero-lag level, while, at high stress levels, the histograms shifted to longer lag phases with a significant increase in variability.Thirdly, 37 different distribution types were fitted to the datasets to reveal the distributions that fitted best the obtained data. The gamma distribution was preferred at moderate stress levels, while the Weibull distribution was chosen for harsher growth conditions.     

Inhibitory effect of the essential oil of Curcuma longa L. and curcumin on aflatoxin production by Aspergillus flavus Link

Aflatoxins are highly toxic, mutagenic, teratogenic and carcinogenic mycotoxins. Consumption of aflatoxin-contaminated food and commodities poses serious hazards to the health of humans and animals. Turmeric, Curcuma longa L., is a native plant of Southeast Asia and has antimicrobial, antioxidant and antifungal properties. This paper reports the antiaflatoxigenic activities of the essential oil of C. longa and curcumin. The medium tests were prepared with the oil of C. longa, and the curcumin standard at concentrations varied from 0.01% to 5.0%. All doses of the essential oil of the plant and the curcumin standard interfered with mycotoxin production. Both the essential oil and curcumin significantly inhibited the production of aflatoxins; the 0.5% level had a greater than 96% inhibitory effect. The levels of aflatoxin B₁ (AFB₁) production were 1.0 and 42.7 μg/mL, respectively, for the samples treated with the essential oil of C. longa L. and curcumin at a concentration of 0.5%.     

Effects of steaming the root of Panax notoginseng on chemical composition and anticancer activities

The root of Panax notoginseng has been shown to change its saponin composition upon steaming. This study examines the effects of different steaming times and temperature on notoginseng root for saponin composition and anticancer activities. Steaming decreased the content of notoginsenoside R1, ginsenosides Rg1, Re, Rb1, Rc, R2, Rb3 and Rd, but increased the content of Rh1, Rg2, 20R-Rg2, Rg3 and Rh2. Steaming significantly influenced the transformation of Rg3. The amount of ginsenoside Rg3, an anticancer compound, was 5.23-fold greater in root steamed for 2 h at 120 °C than at 100 °C, and 3.22-fold greater when steamed for 4 h than for 1 h at 120 °C. For anticancer effects, the extract of steamed root significantly inhibited proliferation of SW-480 human colorectal cancer cells. The IC₅₀ of the steamed extract for 1, 2, 4 and 6 h at 120 °C was 259.2, 131.4, 123.7 and 127.1 μg/mL, respectively; the effect of unsteamed extract was low. Flow cytometric analysis demonstrated that the apoptotic cell induction rates of SW-480 cells were 56.3% and 64.4% with 150.0 and 200.0 μg/mL extract steamed for 6 h. Compared with Rg1 and Rb1, only Rg3 had a significant antiproliferative effect.     

Effect of storage temperature and gas permeability of packaging film on the growth of lactic acid bacteria and Brochothrix thermosphacta in cooked meat emulsions

The effect of gas permeability of packaging film on the growth of lactic acid bacteria and Brochothrix thermosphacta in cooked meat emulsions stored at 0, 8 and 15 °C was investigated. The estimated parameters from Gompertz equation for the assayed temperature–oxygen permeability combinations showed LAB development to be significantly greater than those of B. thermosphacta. The influence of the two sources of variation (oxygen permeability of packaging film and temperature) on the growth parameters of LAB and B. thermosphacta was analysed showing a significant effect (P<0.001) of the temperature on both bacterial population while the film permeability had only a significant influence (P<0.001) on B. thermosphacta growth. Under the conditions of this study the packaging film influenced the maximum counts and growth rates of both organisms. Since the inhibition of B. thermosphacta occurred when the meat product was vacuum-packaged in films possessing high oxygen permeability and the effect of pH was found not to be associated with the growth inhibition, accumulation of hydrogen peroxide produced by LAB may possibly be one of the main factors responsible for B. thermosphacta inhibition. Shelf-life of vacuum-packaged cooked meat emulsions in high oxygen transmission rate films will be guarantied and a temperature abuse will not result in an increase of spoilage by LAB.     

In vivo and in vitro studies to identify the hypoglycaemic constituents of Momordica charantia wild variant WB24

Wild bitter melon (the wild variant of Momordica charantia L.) native to the eastern region of Taiwan has been consumed by local residents as a folk medicine for the prevention or treatment of hyperglycaemia and related diseases, yet its hypoglycaemic activities and constituents have not been scientifically characterised. Thus, WB24, a strain of wild bitter melon originating from the eastern region of Taiwan, was investigated. By cell-based screening, the fruit of WB24 was revealed to be a rich source of hypoglycaemic molecules, and the in vivo hypoglycaemic activities of selected fractions were assessed. Five triterpenes were isolated from one of the most active fractions and their ability to activate AMP-activated protein kinase (AMPK) was observed. One triterpene of the five analysed exhibited the highest activation of AMPK in an insulin-independent manner, and the AMPK-activation activity of this triterpene was greater than that of troglitazone, a thiazolidinedione-type antidiabetic medicine.