• Clinical and Experimental Reproductive Medicine
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• 제32권4호
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• pp.301-314
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• 2005

Objective: Rebamipide is a propionic acid derivative that has an action of the inhibition of superoxide production and removal of hydroxyl radical with the sperm incubation and cryopreservation. In the present study, to investigate whether rebamipide is useful to treat male infertility and sterility, the author observed the antioxidative effects in patient with male infertility and also examined its absorption and distribution in rat genital organ. Methods: To measure the distribution of rebamipide in reproductive organ in the rat, carbon indicated rebamipide, $^{14}C-OPC-12759$, was orally administered to 10 Spraque-Dawley rats and its organ concentration in serum, liver, kidney, stomach, duodenum, colon, urinary bladder, seminal vesicle, epididymis and testicle were measured each time after 0.5, 1, 2, 4, 8 and 24 hours by using HPLC fluorescent method. The concentrations in semen were measured by HPLC fluorescent method in a sample of 50 infertile males who took 900 mg of rebamipide daily for 3 months. To measure the antioxidative effect and fertility rate for 3 months, each month before and after the treatment, sperm motility, vitality, the oxygen free radical formation, level of peroxidation, fetilizing capacity of semen sample which were obtained from infertile male patients by masturbation after at least 48 hours abstinence were analyzed by computer assisted semen analyzer, eosin-nigrosin stain, chemiluminescence, thiobarbituric acid method and hypo-osmotic swelling test. Simultaneously in a sample that wanted baby, both pregnancy and delivery were researched. Results: The $^{14}C-OPC-12759$ concentration in the body of white rats was highest in gastrointestinal organ like stomach, smal intestine and duodenum and followed by genital organ like seminal vesicle, testis and epididymis. The rebamipide concentration in semen of infertile males was $220.77{\pm}327.84ng/mL$ (SD) which showed a large deviation but it was higher than serum which was $126{\pm}76ng/mL$ (SD). In the infertile males, after the treatment with rebamipide, the level of seminal reactive oxygen species (ROS) and lipid peroxidation have significantly decreased in duration of the treatment (p<0.05) and sperm vitality and fertilizing capacity except sperm motility significantly improved on post treatment of 2~3 months (p<0.05). Out of the 41 cases who hoped for pregnancy, 15 cases (36.6%) became pregnant and 12 cases had childbrith, 2 cases had miscarriage and one case is ongoing. The side effect was observed in 1 case (2%) which experienced diarrhea but it was lost spontaneously. Conclusions: We conclude from this study that rebamipide showed relatively high tendancy of absorption and excretion in the genital organ. In infertile males who had elevated ROS in semen, by specifically inhibiting the cell damage from the antioxidation, a way to preserve sperm motility, vitality and fertilizing capacity was confirmed.

• Journal of Pharmaceutical Investigation
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• 제32권2호
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• pp.127-133
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• 2002

Levosulpiride is the 1evo-enantiomer form of racemic sulpiride, a benzamide derivative selectively inhibiting dopaminergic $D_2$ receptors at the trigger zone both in the central nervous system and in the gastrointestinal tract. The purpose of the present study was to evaluate the bioequiva1ence of two levosulpiride tablets, Levopride (SK Pharmaceutical Co., Ltd.) and Levopid (Dae Won Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The levosulpiride release from the two levosulpiride tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight normal male volunteers, $23.82{\pm}3.26$ years in age and $69.13{\pm}8.58$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg of levosulpiride was orally administered, blood was taken at predetermined time intervals and the concentrations of levosulpiride in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two levosulpiride tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the Levopride were -1.17%, 1.20% and -1.09%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.93){\sim}log(1.07)\;and\;log(0.90){\sim}log(1.14)\;for\;AUC_t\;and\;C_{max}$, respectively). The 90% confidence interval using untransformed data was within ${\pm}20%$ $(e.g.,\;-19.47{\sim}16.20\;for\;T_{max})$. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Levopid tablet is bioequivalent to Levopride tablet.

• Journal of Pharmaceutical Investigation
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• 제41권2호
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• pp.117-123
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• 2011

Loxoprofen sodium, a 2-phenylpropionate non-steroidal anti-inflammatory drug (NSAID), has marked analgesic and antipyretic activities and relatively weak gastrointestinal ulcerogenicity. The purpose of the present study was to evaluate the bioequivalence of two loxoprofen sodium tablets, Hana loxoprofen sodium tablet (Hana Pharm. Co., Ltd.) and Dongwha Loxonin$^{(R)}$ tablet (Dongwha Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of loxoprofen from the two loxoprofen sodium formulations was tested using KP IX Apparatus II method with various dissolution media. Twenty four healthy Korean male volunteers, $22.83{\pm}1.862$ years in age and $69.92{\pm}9.14$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After a single tablet containing 60 mg as loxoprofen sodium was orally administered, blood samples were taken at predetermined time intervals and the concentrations of loxoprofen in serum were determined using a online column-switching HPLC method with UV/Vis detection. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC^t$, $C_{max}$ and $T_{max}$ were calculated, and computer programs (Equiv Test and K-BE Test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and un-transformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Dongwha Loxonin$^{(R)}$ tablet, were 2.03, 2.99 and -9.49% for $AUC_t$, $C_{max}$, and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log0.8 to log1.25 (e.g., log0.9831~log1.0535 and log0.9455~log1.1386 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Hana loxoprofen sodium tablet was bioequivalent to Dongwha Loxonin$^{(R)}$ tablet.

• Journal of Korean Neurosurgical Society
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• 제61권5호
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• pp.633-639
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• 2018

Objective : We investigated the outcomes of repeat stereotactic radiosurgery (SRS) for metastatic brain tumors that locally recurred despite previous SRS, focusing on the tumor control. Methods : A total of 114 patients with 176 locally recurring metastatic brain tumors underwent repeat SRS after previous SRS. The mean age was 59.4 years (range, 33 to 85), and there were 68 male and 46 female patients. The primary cancer types were non-small cell lung cancer (n=67), small cell lung cancer (n=12), gastrointestinal tract cancer (n=15), breast cancer (n=10), and others (n=10). The number of patients with a single recurring metastasis was 95 (79.8%), and another 19 had multiple recurrences. At the time of the repeat SRS, the mean volume of the locally recurring tumors was 5.94 mL (range, 0.42 to 29.94). We prescribed a mean margin dose of 17.04 Gy (range, 12 to 24) to the isodose line at the tumor border primarily using a 50% isodose line. Results : After the repeat SRS, we obtained clinical and magnetic resonance imaging follow-up data for 84 patients (73.7%) with a total of 108 tumors. The tumor control rate was 53.5% (58 of the 108), and the median and mean progression-free survival (PFS) periods were 246 and 383 days, respectively. The prognostic factors that were significantly related to better tumor control were prescription radiation dose of 16 Gy (p=0.000) and tumor volume less than both 4 mL (p=0.001) and 10 mL at the repeat SRS (p=0.008). The overall survival (OS) periods for all 114 patients after repeat SRS varied from 1 to 56 months, and median and mean OS periods were 229 and 404 days after the repeat SRS, respectively. The main cause of death was systemic problems including pulmonary dysfunction (n=58, 51%), and the identified direct or suspected brain-related death rate was around 20%. Conclusion : The tumor control following repeat SRS for locally recurring metastatic brain tumors after a previous SRS is relatively lower than that for primary SRS. However, both low tumor volume and high prescription radiation dose were significantly related to the tumor control following repeat SRS for these tumors after previous SRS, which is a general understanding of primary SRS for metastatic brain tumors.

• Tuberculosis and Respiratory Diseases
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• 제60권2호
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• pp.180-186
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• 2006

배경: 다제내성 결핵환자에서 이차약제로 구성된 처방 복약시 특히 PAS는 심한 위장장애 등의 부작용으로 환자의 치료순응도 저하에 중요한 요인이 되므로 균음전 후 PAS를 처방에서 제외한 경우의 치료경과 특히, 치료종결 후 재발율에 대한 조사를 통해 치료경과 중에 적절한 시점에 처방에서 PAS제외 가능성에 대하여 평가하고자 하였다. 방법: 2000년 1월 1일부터 2001년 12월 31일 동안에 국립마산결핵병원에서 입원 혹은 외래치료를 받았던 452명의 다제내성 결핵환자 중에서 처방에 PAS가 포함된 194명 중 심한 위장장애 등의 부작용 때문에 PAS를 중단한 환자 중 균음전 후 PAS를 제외한 처방을 12개월 이상 유지할 수 있었던 42명을 대상으로 임상적 특성 및 치료종결 후 재발율을 분석하였다. 결과: 대상환자의 남녀성비는 2.5:1, 평균나이는 56.2세였다. 1.2회의 과거치료력이 있었으며, 사용한 약제는 평균 3.9제였다. 내성약제수는 평균 4.3제였으며 처방에 포함된 감수성약제수는 평균 3.9제였다. 치료가 시작된 후 균음전시기는 평균 2.3개월째였으며, PAS 중단 시기는 균음전 후 평균 6개월째였다. 31.6개월의 추구관찰 기간 중 재발환자는 없었다. 결론: 새로운 항결핵제의 개발이 요원하고, 다제내성 결핵에 사용가능한 약제가 제한된 현 상황에서 치료순응도 개선방안을 강구하는 것은 치료효율을 높일 수 있는 최선의 방법 중 하나라고 생각되며, 다제내성 결핵환자에서 PAS가 포함된 처방으로 균음전이 되고 환자가 PAS복약에 따른 부작용을 호소하여 치료순응도가 나빠질 것으로 염려가 되면 균음전 후 6개월 즈음에는 PAS를 처방에서 제외할 수 있을 것으로 판단되었다.

• 한국보건간호학회지
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• 제12권2호
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• pp.221-235
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• 1998

This study is a descriptive survey to explore the health lifestyle of adults. The study subjects are teachers of elementary. middle and high school. and staffs of research institutes located in Chungchung Province and Daejon city. The data was collected from Jan. to march 1997 through self reporte for structured questionnaire. Fantastic check list of Wilson and Ciliska for Health Lifestyle Assessment and DSM-III-R for somatic symptom were used as tools. Data was analysed by frequency, $X^2_test$, t-test and Anova using SAS program. The results are as follows: 1. There were statistically significant differences In drinking(t=7.75, P=.000), exercise(t=-2.99, P=.003)and interpersonal relationship(t=2.22, P=.027) among 10 health lifestyle between smoking group and non-smoking group, in drinking(t=17.98, P=.000), exercise(-4.71. P=.000), and job satisfaction(t=2.22, P=.027) between drinking group and non-drinking group, and in eating habit(t=-2.00, P=.045), drinking (t=4.47, P=000), exercise (t= -16.49, P=000), keeping traffic law(t= -2.68, P=.007), personality (t= -2.05, P=.040) and anxiety/depression(t=-3.47, P=.000) between exercise group and non-exercise group. 2. There was statistically significant difference in cardiovascular symptom(F=4.22, P=.0l) among somatic symptoms of subjects according to exercise level. 3. There was statistically significance difference in lifestyle according to smoking level(F=, 3.33, P=.011), drinking level(F=9.17, P=.0001) and exercise level(F=11.93, P=.000l), and in somatic symptom according to sex(t=-3.93, P=.0001), weight(F=3.83, P=.022), exercise level (F=3.29, P=.03) among general characteristics. 4. There was statistically significant difference between sex in general (t= -3.64, P=.0001), gastrointestinal(t=-2.21, P=.02), musculoskeletal(t=-3.92, P=.001), and total symptom (t= -3.92, P=.0001). 5. There was statistically very highly signigicant difference In weight according to smoking($x^2=25.18,\; P=.001)$ and exercise$(x^2=16.46,\; P=001)$. 6. There was statistically significant difference in frequency between smoking group, drinking group and exercise group$(x^2=24.52,\;P=.001)$. Among a number of habit, smoking, drinking and exercise are important factors of human health to prevent related disease morbidity and death. It is essential for industrial health nurse to committ in this subject considering the influence of those factors and lifestyle on health. There is also a relationship of weight with smoking and exercise, the frequency of overweight/obesiy in smoking/ no-exercise group were high. It is quite necessary for the people having cardiovascular symptom to exercise to lower morbidity and mortality. The industrial health nurse has to keep In mind on this point and consider of time and facilities of fitness of employee. It needs to explore the cause by further research on somatic symptom of women. This research shows that concerning the relationship between smoking, drinking, and exercise, health care provider must take not only management of disease, but health behaviors and lifestyle into consideration.

• 대한핵의학회지
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• 제1권2호
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• pp.61-74
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• 1967

In order to confirm whether acquired immunity or resistance can be developed by the repeated hookworm infections, the 150 mature actively moving filariform ancylostoma duodenale larvae obtained from the severe hookworm anemia patients were orally given to 8 healthy volunteers in three divided doses, 50 in each, at 5 day interval. Also the hematological changes as well as several ferrokinetics using $^{59}Fe$ were done and were compared with 10 controls. The clinical symptoms and signs were checked every day for the first 3 weeks and then twice weekly until the end of the experiment. The appearance of the ova in the stool was examined by the formalin ether method and the ova was counted by the Stoll's method. The following laboratory tests were done: 1) Red blood cell count, venous blood hematocrit(micromethod), hemoglobin count (cyanomethemoglobin method) were checked every 5 to 7 day interval. 2) Plasma iron concentration (Barkan's modified method) was determined every 2 to 3 week interval. 3) Radioisotope studies: a) Ferrokinetics: Huff et al and Bothwell's method were applied. Erythropoietic Index (% of normal)=$\frac{Subject's\;turnover/100ml\;whole\;blood{\times}100}{Average\;normal\;turnover/100ml\;whole\;blood}$ of the gastrointestinal absorption of iron: Radioiron($^{59}Fe$) balance b) Quantitative measurement method was applied. c) Determination of the plasma erythropoietin activity: Fried's method was applied. Following were the results: 1) The serum iron level was lower. The red cell volume was decreased, but with relative increase of plasma volume. 2) The plasma iron disappearance time was accelerated and the plasma iron turnover rate was decreased. The red cell iron turnover rate was markedly increased, while all of the red cell iron concentration, circulating red cell iron. plasma iron pool were decreased. The daily iron pool turnover and red cell renewal rate were increased. 3) The erythropoietic index, erythropoietin activity and intestinal absorption of iron($^{59}Fe$) were markedly increased. 4) The infectivity was $9.8{\pm}1.31%$ which was lower than that observed in the single infection. 5) From these observations, it is concluded that the hookworm anemia is essentially iron deficieny in its origin and some immunity acquisition is possible with repeated infections.

• 한국축산식품학회:학술대회논문집
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• 한국축산식품학회 2001년도 임시총회 및 제28차 추계학술발표회
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• pp.43-56
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• 2001

Colostrum contains various kinds of cytokines including TGF-${\beta}$ which is known to be multifunctional in immune response and act as an anti-inflammatory agent. First, we measured the amount of TGF-${\beta}$ in bovine and human colostrum. Expression pattern of TGF-${\beta}$ isotypes was dramatically different between human and bovine colostrial samples. Bovine colostrum collected on day 1 post-delivery retained $41.79{\pm}16.96ng/ml$ of TGF-${\beta}$ 1 and $108.4{\pm}78.65ng/ml$ of TGF-${\beta}$ 2 while in human, $284{\pm}124.75ng/ml$ of TGF-${\beta}$ 1 and $29.75{\pm}6.73ng/ml$ of TGF-${\beta}$ 2. Thus, TGF-${\beta}$ is the predominant TGF-${\beta}$ isotype in bovine colostrum and vice versa in human colostrum. Both TGF-${\beta}$ isotypes diminished significantly in human and bovine colostrum with time. Next, biological activity of colostrial samples was examined in vitro. Both human and bovine colostrum increased IgA synthesis by LPS-activated mouse spleen B cells, which is a typical effect of TGF-${\beta}$ on the mouse B cell differentiation. Futhermore, we found that anti-proliferative activity in MV1LU cells by colostrum samples disappeared by addition of anti-TGF-${\beta}$ 1 and anti-TGF-${\beta}$ 2 antibody. In conclusion, there are substantial amounts of biologically active TGF-${\beta}$ 1 and TGF-${\beta}$ 2 in bovine and human colostrum. The results that the colostrum can increase IgA expression has important implications since IgA is the major Ig class produced in the gastrointestinal tract. We have previously shown that the stimulatory effect of Bifidobacteria bifidum on spllen B cells was quite similar to that of LPS which is a well-known polyclonal activator for murine B cells. In the present study, we further asked whether B. bifidum regulate the synthesis of IgA by mucosal lymphoid cells present in Peyers patches (PP) and mesenteric lymph nodes (MLN). B. bifidum alone, but not C. perfringens, significantly induced overall IgA and IgM synthesis by both MLN and PP cells. This observation indicates that B. bifidum possesses a modulatory effect on the mucosal antibody production in vivo. We, therefore, investigated the mucosal antibody prodduction following peroral administration of B. bifidum to mice. Ingested B. bifidum significantly increased the numbers of Ig (IgM, IgG, and IgA) secreting cells in the culture of both MLN and spleen cells, indicating that peroally introduced B. bifidum enhances mucosal and systemic antibody response. Importantly, however, B. bifidum itself does not induce the own specific antibody responses, implying that B. bifidum do not incite any unwanted immune reaction. Subsequently, it was found that excapsulation of B. bifidum further augments the total IgA production by increasing the number of IgA-secreting cells in the culture of both MLN and spleen cells. Finally, we found that the immuno-stimulating activity of B. bifidum is due to its cell wall components but not due to any actively secreting component(s) from bacteria. Thus our data reveal that peroral administration of B. bifidum can enhance intestinal IgA production and that encapsulation of B. bifidum further reinforces the IgA production.

• 한국식품과학회지
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• 제28권4호
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• pp.689-695
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• 1996

보리가루로부터 ${\beta}-Glucan$을 추출, 정제하여 그의 소화관내 생리적 기능성을 알아보기 위해 반투막을 이용한 in vitro실험을 수행하였다. 보리가루로부터 ${\beta}-Glucan$을 6.2%의 수율로 정제하였으며 그의 순도를 확인한 결과 총 식이섬유 81.6%, 수용성 식이섬유 72.9%, 불용성 식이섬유 8.7%, 수분 8.5%, 단백질 2.5%, 회분 7.4%였다. ${\beta}-Glucan$ 제품의 수분보유력은 1g의 건조물당 6g이었다. 투석막을 이용하여 ${\beta}-Glucan$ 제품의 glucose 흡수 지연효과를 살펴 본 결과 ${\beta}-Glucan$을 3% 첨가한 경우 투석 30분이 경과되었을 때 glucose retardation index가 13.5%였고 시간이 경과할수록 그 효과는 감소하여 투석 2시간 후에는 그 효과가 거의 없는 것으로 나타났다. Bile acid 흡수 지연 효과를 살펴 본 결과 투석 30분이 경과되었을 때 bile acid retardation index는 ${\beta}-Glucan$이 1, 3, 5% 첨가된 경우 각각 3, 12, 18% 수준으로 같은 시간이 경과되었을 때의 glucose 흡수 지연 효과보다 더 크게 나타났으며 시간이 경과할수록 그 효과가 감소하였다.

• 한국식품과학회지
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• 제38권3호
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• pp.427-431
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• 2006

췌장에 ${\beta}-cell$에만 특이적으로 작용하고 다른 기관에는 영향을 주지 않는 것으로 보고되어 있는 streptozotocin을 흰쥐에게 투여하여 당뇨병을 유발시킨 다음 백미, 현미, 거대배아미를 6주간 급여한 후 혈당강화 효과를 알아보았다. 실험기간동안 모든 당뇨군들의 체중증가는 정상군에 비해서는 유의적으로 낮았다. 당뇨대조군에 비해서는 거대배아마를 급여한 군에서 체중감소현상이 억제되었다. 장기중 맹장의 경우 2배 이상의 비대현상이 나타났고 정상쥐에 비해 당뇨쥐가 수분섭취량, 소변배설량, 혈당이 유의적으로 높게 나타났는데 당뇨병의 주요 증세가 다갈(polydipsia), 다뇨(polyuria), 다식(polyphagia), 고혈당인점에서 당뇨군에 비해서 가대배아미는 당뇨증세가 어느 정도 호전효과가 있음을 보여주고 있다. 식이섭취량은 정상군에 비해 당뇨실험군들이 높게 나타났으며 수분섭취량은 정상군에 비해 당뇨대조군이 수분 섭취량증가가 나타났다. 당뇨실험군 내에서는 당뇨대조군에 비해 가대배아미군이 수분섭취량이 감소하였다. 뇨 배설량은 정상군에 비해 당뇨대조군이 유의적으로 높게 나타났으며 당뇨대조군에 비해서 거대배아미군이 감소하였다. 장 기능 조절로서 장통과 시간과 분변고형물의 양에는 역의 상관관계로 식이섬유소의 함량이 높은 쌀 품종인 거대배아미는 장통과 시간이 짧으며 분변고형물의 양을 유의적으로 증가시켰으며 변의 수분보유량도 정상군에 비해 당뇨실험군들중 거대배아미군 전반적으로 높았다. 위 결과에서 거대배아미 급여가 당뇨동물의 공복시 혈당 수준을 유의적으로 낮추는데 효과가 있었으며 이당류 분해 효소 활성의 경우 정상군에 비해서 당뇨군이 lactase, maltase, sucrase 활성이 현저하게 증가 되었지만 당뇨실험군중에는 거대배아미가 소장점막부분의 lactase, maltase, sucrase의 활성을 저해시킴으로서 혈당상승을 억제시키는 것으로 볼 수 있었다. 이상의 결과로 백미, 현미에 비해서 거대배아미를 급여한 당뇨동물에서 혈당을 억제시키는 효과를 보았다.