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게 르 마 늄 논 문 집

간 독 성 경 감
1. 유기게르마늄(Ge-132)이 Glutathione S-transferase 활성에 미치는 영향 (한국영양식량학회지)
2. 유기게르마늄이 간 독성에 미치는 영향 (동아대 가정교육)

   성 
 1. 유기게르마늄의 정맥 내 투여 후 비글개의 6개월 간 만성 독성 실험 (응용약리)
 2. 화학합성 유기게르마늄과 비교할 때 무기게르마늄에 의해 야기되어지는 만성 관간질의 변화(국제신장학회)
 3. 시험관 내에서 스피로 게르마늄의 독성 및 생물학적 특성 (암연구)

돌 연 변 이 억 제
 1. Benzopyrene의 돌연변이원성에 대한 유기게르마늄(Ge-132)의 항돌연변이 효과 (약학회지)
 2. 벤조피렌에 의한 돌연변이에서 미량원소의 변형 역할 (돌연변이 연구)
 3. 게르마늄 화합물의 돌연변이성, 발암성과 기형발생성 (돌연변이 연구
)

면 역 조 절
 1. 스피로게르마늄을 먹인 루이스 쥐에서 실험실적인 자가면역 뇌척수염의 억제의 1차적인 연구  (신경질병학과 실험신경학)
 2. 스피로 게르마늄의 항관절염과 면역조절 활성 (약학과 실험 치료학)

면 역 활 성
1.면역부활제에 의한 인터페론 유도와 NK세포 활성증강 작용 (의학의 흐름)
2.Ge-132가 시험관에서 인체 NK세포활성에 미치는 영향 (의학과 생물학)
3.비글개에 있어서 Ge-132에 의한 NK세포 활성증강에 관하여 (의학과 약학)
4.카드뮴, 아연, 및 유기게르마늄이 일차면역 반응에 미치는 영향에 관한 연구 (연대 의학과)
5.유기게르마늄의 경구투여한 쥐에서 인터페론의 유도와 NK세포, 마크로파지의 활성화 (미생물 면역학)
6.유기게르마늄 화합물 투여에 의한 2-5A 합성효소의 유도 (의학과 약학)
7.인터페론 및 인터페론 유도제에 관한 기초적, 임상적 연구 (오까야마의학지)
8.게르마늄이 대식세포의 활성화에 미치는 영향 (전북대 의학과)

백 내 장
 1. 게르마늄-132의 백내장에 대한 효과 (눈연구 동향)

산 소 공 급
 1. 초건강을 위한 산소-영양소 (정분자의학)

암 발 생 억 제
1. 일부 필수 미량원소 결핍의 결과로서의 발암현상 (의학적 학설)
2. 디에틸니트로사민에 의해 발생되는 쥐 간암 발생에 있어서 알릴설피드, 게르마늄과 NaCl의 영향 (항암연구)
3. 쥐의 다기관 발암현상 모델에서 알릴 설피드, 인돌-3-카비놀과 게르마늄의 변형작용 (발암현상)

약 리 효 과
1. 유기게르마늄의 치료효능 (의학적학설)
2. 식물성 게르마늄화합물에 관하여 (와다나베)
3. 게르마늄 화합물의 일반약리작용에 관한 연구 (응용약리)
4. 유기게르마늄 화합물인 Ge-132의 약리활성 (의학과 약학)

     통
1. 엔케팔린 분해효소 유도에서 Ge-132의 통각억제 효과 (생명과학과 응용 생화학)

콜 레 스 테 롤  저 하
1. 13가지 미량원소를 먹인 쥐에서 혈중 콜레스테롤 수치 (식량학회)

항 바 이 러 스 효 과
1. 유기게르마늄 화합물 Ge-132의 백시니아 바이러스 감염억제 작용

항 산 화 작 용
1. 낮은 농도의 셀레늄 함유 곡물을 먹인 쥐에서 셀레늄, 게르마늄이 지질과산화에 미치는 영향  (중국예방의학회지) 

항 암 효 과
1. Ge-132에 의한 L1210 백혈병세포의 열발생 (의학과 생물학)
2. Ge-132를 처리한 L1210 세포의 전자현미경 관찰 (의학과 생물학)
3. 유기게르마늄을 투여한 쥐에서 분리한 혈청의 항암활성 (암과 화학요법)
4. 유기게르마늄 화합물의 항종양효과 : 투여경로별 효과의 비교 (암과 화학요법)
5. 유기게르마늄을 투여한 쥐에서 분리한 마크로파지의 항종양활성 (암과 화학요법)
6. Sarcoma 180 유발 생쥐에 미치는 amygdaline과 carboxyethyl-germanium sesquioxide의  단독 및 병합 투여의영향      (서울 보건대 논문집)
7. 암에 걸린 쥐에서 유기게르마늄의 항암효과 기전(carboxyethyl-germanium sesquioxide) (암과 화학요법)

혈 압 조 절
1. 쥐의 심혈관 기능과 박동에 있어서 유기게르마늄의 효과 (약리학)


                                                                                                                            
간 독 성 경 감

1. 유기게르마늄(Ge-132)이 Glutathione S-transferase 활성에 미치는 영향 (한국영양식량학회지)

The Study of Pretreated GE-132 on the Hepatic Glutathione S-Transferase Activity in Rat
Seok-Hwan Kim, Eun-Sook Park, Tae-Hyun Jo and Jong-Won Choi
Dept. of Food Science and Nutrition, Dong-A University,
Dept. of Pharmacy, Kyungsung University

Abstract

The study was initiated to elucidate the mechanism by examining the effect of GE-132 on hepatic glutathione S-transferase (GST) activity. Activity of GST increased with dose-dependent manner in hepatic cytosolic fraction of GE-132 treatment rats. Double reciprocal plotting gave Vmax value 1.4 fold increase by the treatment of GE-132 (100mg/kg, p.o. for 6 weeks) compared with control group, but did not change Km value. Ethacrynic acid (85mg/kg, once a day, i.p.) was injected to control rat, the GST activity decreased remarkably. However, GE-132 pretreated group, the effect caused by ethacrynic acid was markedly reduced. And activity of g -glutamylcysteine synthetase was not changed either by GE-132 treatment, but the activity of glutathione reductase increased significantly. Decreasing properties of ethacrynic acid decreased level of hepatic glutathione, which was restored to same degree by GE-132 pretreatment. GE-132 also protective effect on ethacrynic acid-induced mortality. It is concluded that the effect of GE-132 is partly mediated by increase in hepatic GST activity.
Source: J Korean Soc Food Nutr. 1994. 23(4), 581 ? 586.

2. 유기게르마늄이 간 독성에 미치는 영향 (동아대 가정교육)

Effect of Germanium on the hepatotoxicity in rat
Park Eun-Sook
Graduate School of Education, Dong-A University

Abstract

The study was initiated to elucidate the mechanism by examine the effects of Ge-132 (100mg/kg, p.o. for 6 weeks) on the glutathione S-transferase (GST) activity of ethacrynic acid, which has potent nephrotoxicity, hepatotoxicity and cardiac necrosis. It showed that activity of GST was increased with dose dependent manner in hepatic cytosolic fraction of Ge-132 treatment rats, and the enzyme activity was significantly elevated as compared to control group. When plotted on double reciprocal from the Vmax value was increased about 1.4 fold by the treatment of Ge-132 compared to control group, but Km value was not changed. Ethacrynic acid (85mg/kg, once a day, i.p.) was injected to control rat, the GST activity was powerfully decreased. However, GE-132 pretreated group, the decreasing effect caused by ethacrynic acid was markedly reduced. And also activity of g -glutamylcysteine synthetase was not changed either by GE-132 treatment, but the activity of glutathione reductase was significantly increased significantly. Decreasing properties of ethacrynic acid on the hepatic glutathione was shown to be recovered markedly by GE-132 pretreatment. Consequently, it was observed that the mechanism for the protective effect of GE-132 on ethacrynic acid-induced mortality is due to the indirectly induction of GST.
Source: Dong-A Univ. Pusan, Korea. 1994

 


 


 

 

..

 

   성 

1. 유기게르마늄의 정맥 내 투여 후 비글개의 6개월 간 만성 독성 실험 (응용약리)

Cytotoxic Effects and Biological Activity of 2-Aza-8-germanspiro[4,5] decane-2 -propanamine- 8,8-diethyl- N,N-dimethyl Dichloride (NSC 192965; Spirogermanium) in Vitro
Bridget T. Hill, S. A. Whatley, Angela S. Bellamy, Lorraine Y. Jenkins, and R. D. H. Whelan
Laboratory of Cellular, Chemotherapy
Cancer Research Fund, Lincoln's Inn Field, London, England

ABSTRACT

Lethal and other biological effects of 2-aza-8-germanspiro[4,5]decane-2-propanamine-8,8-diethyl-N,N-dimethyl dichloride (NSC 192965; spirogermanium), representing a new chemical class of compound exhibiting antitumor activity, have been studied in vitro. Survival curves for NIL 8 hamster cells were exponential with greater kill occurring with) increasing drug concentrations and longer exposure times. Cytotoxicity was temperature dependent. "Quiescent" cultures were significantly less sensitive to spirogermanitim than were logarithmically growing cells. These lethal effects showed no phase specificity. There was no evidence of progression delay through the cycle following spirogermanium treatment.

When spirogermanium was tested against a range of human cell lines, the consistency of the values for (the drug concentration required to reduce survival by 50% on the exponential part of the survival curves), derived from colony-forming assays, was most marked. The survival curves, characterized by an initial shoulder, were steep and exponential with measurements possible over only a narrow concentration range since complete, cell lysis occurred at levels causing a >2-log kill. Cell membrane damage by spirogermanium, as judged by dye exclusion, was progressive with time and increasing drug concentrations. Protein synthesis proved most susceptible to the drug. Spirogermanium concentrations cytotoxic to tumor cells were also toxic to cultured rat neurons, confirming the clinical neurological toxicity encountered.
The precise mode of action of spirogermanium remains to be established, and these data further illustrate its apparent lack of specificity.
Source: Cancer Research. 1982. 42, 2852~2856.

2. 화학합성 유기게르마늄과 비교할 때 무기게르마늄에 의해 야기되어지는 만성 관간질의 변화(국제신장학회)

Chronic tubulointerstitial changes induced by germanium dioxide in comparison with carboxyethylgermanium sesquioxide
TORU SANAI, SEIYA OKUDA, KAORU ONOYAMA, NOBUAKI OOCHI, SHIGEKO TAKAICHI, VINCI MIZUHIRA, and MASATOSHI FUJISHIMA

Abstract

Chronic nephrotoxicity was investigated in rats orally administered germanium dioxide (GeO2) and carboxyethylgermanium sesquioxide (Ge-132) for 24 weeks. Increased BUN and serum phosphate as well as decreased creatinine clearance, weight loss, anemia and liver dysfunction were apparent at week 24 only in the GeO2 treated group. Vacuolar degeneration and granular depositions were observed by light microscope in the degenerated renal distal tubules in the rats of this group, with the semiquantitative scores of tubular degeneration being 95 ± 9% in the GeO2 group. 3 ± 1% in the Ge-132 group and 1 ± 1% in the control group, respectively. Electron microscopy revealed electron-dense inclusions in the swollen mitochondrial matrix of the distal tubular epithelium in the GeO2 group. Although systemic toxicities were reduced after GeO2 was discontinued at week 24, renal tubulointerstitial fibrosis became prominent even at week 40 (l6weeks after discontinuation). A Ge . Ka X-rav spectrum was clearly demonstrated in the mitochondrial matrix of the distal tubular epithelium in the GeO2 group with the help of electron probe X-ray microanalysis. On the other hand, neither toxic effects nor renal histological abnormalities were manifested in either the Ge-132 or the control group. The renal tissue content of germanium was high at weeks 24 and 40 in the GeO2 group. From these results, it is concluded that GeO2 causes characteristic nephropathy while Ge-132 does not. In addition, it appears that residual GeO2 remains for a considerably long time even after the cessation of GeO2 intake.
Source: Kidney International. 1991. 40.

3. 시험관 내에서 스피로 게르마늄의 독성 및 생물학적 특성 (암연구)

Cytotoxic Effects and Biological Activity of 2-Aza-8-germanspiro[4,5]decane-2-propanamine- 8,8-diethyl- N,N-dimethyl Dichloride (NSC 192965; Spirogermanium) in Vitro Bridget  T. Hill,  S. A. Whatley, Angela S. Bellamy, Lorraine Y. Jenkins, and R. D. H. Whelan
Laboratory of Cellular, Chemotherapy
Cancer Research Fund, Lincoln's Inn Field, London, England

ABSTRACT

Lethal and other biological effects of 2-aza-8-germanspiro[4,5]decane-2-propanamine-8,8-diethyl-N,N-dimethyl dichloride (NSC 192965; spirogermanium), representing a new chemical class of compound exhibiting antitumor activity, have been studied in vitro. Survival curves for NIL 8 hamster cells were exponential with greater kill occurring with) increasing drug concentrations and longer exposure times. Cytotoxicity was temperature dependent. "Quiescent" cultures were significantly less sensitive to spirogermanitim than were logarithmically growing cells. These lethal effects showed no phase specificity. There was no evidence of progression delay through the cycle following spirogermanium treatment.

When spirogermanium was tested against a range of human cell lines, the consistency of the values for (the drug concentration required to reduce survival by 50% on the exponential part of the survival curves), derived from colony-forming assays, was most marked. The survival curves, characterized by an initial shoulder, were steep and exponential with measurements possible over only a narrow concentration range since complete, cell lysis occurred at levels causing a >2-log kill. Cell membrane damage by spirogermanium, as judged by dye exclusion, was progressive with time and increasing drug concentrations. Protein synthesis proved most susceptible to the drug. Spirogermanium concentrations cytotoxic to tumor cells were also toxic to cultured rat neurons, confirming the clinical neurological toxicity encountered.

The precise mode of action of spirogermanium remains to be established, and these data further illustrate its apparent lack of specificity.
Source: Cancer Research. 1982. 42, 2852~2856.

돌 연 변 이 억 제

1. Benzopyrene의 돌연변이원성에 대한 유기게르마늄(Ge-132)의 항돌연변이 효과 (약학회지)
Antitumor mechanisms of carboxyethyl germanium sesquioxide in mice bearing Ehrlich ascites tumors  Fujio Suzuki
Dept of Microbiology, Kumamoto University Medical School
 

Abstract

The administration of IFN containing sera (Ge-sera) obtained from Ge-132 treated mice (Ge-mice) or the passive transfer of macrophages (MØ) to mice bearing ascites tumors resulted in inhibition of tumor growth. The cooperative role of Ge-sera and Ge0-MØ in the display of Ge-132 anti tumor activity was studied. When mice were prepared with anti-mouse-IFNg antiserum, no IFN inducing or antitumor activities of the compound were detected. Cytotoxic activities were detected in peritoneal MØ of mice treated with Ge-sera, and passive transfer of these MØ to tumor bearing mice resulted in the inhibition of tumor growth. When tumor bearing mice were pretreated with substances toxic to MØ, no antitumor activity of Ge-sera was obtained. However, Ge-132 antitumor activity was observed in mice depleted of T cells, even though the antitumor effect of the compound itself were not demonstrable in T cell depleted mice. Therefore, a part of the antitumor activity of Ge-132 appears to be expressed as follow: (1) Ge-132 stimulates T cells to produce circulating lymphokine(s) which are inactivated by anti-IFNg treatment; (2) activated MØ are generated from resting MØ by these lymphokine(s); (3) the transplanted tumor are inhibited by these MØ.
 

Source: Jpn. Cancer and Chemotherapy. 1987. 14(1), 127~134.

2. 벤조피렌에 의한 돌연변이에서 미량원소의 변형 역할 (돌연변이 연구)

Modifying role of trace elements on the mutagenicity of benzo[a]pyrene
Byro Olson, James McDonald Jr., Tim Noblitt, Yiming Li, Marisa Ley
Department of Oral Biology, Indiana University School of Dentistry,USA
 

Abstract

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon that is found in tobacco smoke and various environmental contaminants and has been shown to be carcinogenic and mutagenic in animal and cell culture studies, respectively. Research studies suggest that various nutritional factors such as the antioxidant vitamins and selenium are very promising as potential anticarcinogenic agents. Moreover, some evidence exists showing that both iron and germanium, at specific dosage levels, may possess antimutagenic potential. This study examined the influence of ferrous sulfate and germanium oxide, independently, upon the mutagenic potential of BaP in the Ames test. Four test strains of Salmonella typhimurium were exposed to BaP (15 ug/plate) in the presence of different dosage levels of iron (0-1000 ug/plate) and germanium (0-600 ug/plate). In the case of iron, it was observed that, depending upon the strain tested, iron reduced BaP’s mutagenicity. In strain TA98, this was a significant effect at 100 ug/plate and higher. In strains TA97a and TA1OO, iron concentrations had to reach 250 ug/plate or higher to produce significant effects. Iron was much less effective in reducing BaP mutagenicity in strain TA102. In general, germanium was not as effective in reducing the mutagenic potential of BaP. Only in the case of the highest concentrations tested (400 and 600 ug/plate) was any effect noted, and this in only three of the four strains evaluated.
 

Source: Mutation Research. 1995. 335, 21~26.

3. 게르마늄 화합물의 돌연변이성, 발암성과 기형발생성 (돌연변이 연구)

Mutagenicity, Carcinogenicity and Teratogenicity of Germanium Compounds
G.B. Gerber, A. Leonard
Teratogenicity and Mutagenicity Unit, Catholic University of Lourain, Belgium

Abstract

The metalloid germanium has found widespread application in electronics, nuclear sciences and medicine. General toxicity of germanium is low, except for the tetrahydride germane, and few observations on toxicity of germanium in man exist. Germanium is not carcinogenic and even appears to inhibit cancer development and, in the form of the organic germanium compound, spirogermanium, to destroy cancer cells. Germanium compounds have no mutagenic activity and may, under certain conditions, inhibit the mutagenic activity of other substances. High doses of germanium may result in an increased embryonic resorption, but possible malformations have been reported only after administration of dimethyl germanium oxide to pregnant animals. Germanium may thus be considered an element of rather low risk to man.
 

Source: Mutation Research. 1997. 387, 141~146.

면 역 조 절

1. 스피로게르마늄을 먹인 루이스 쥐에서 실험실적인 자가면역 뇌척수염의 억제의 1차적인 연구 
      (신경질병학과 실험신경학)

Preliminary study on the suppression of autoimmune encephalomyelitis in the Lewis rat with spirogermanium

Harry J. Sack, Vicki Braunstein, and Celia F, Brosnan
Dept. of Pathology, Albert Einstein College of Medicine.

Abstract

Spirogermanium (SG) is an azaspirane compound that incorporates the element germanium into a heterocyclic ring structure. It is currently being tested in phase II clinical trials as an anti-neoplastic agent and, in experimental animals, has suppressed adjuvant arthritis. In this study, SG suppressed experimental autoimmune encephalomyelitis in the Lewis rat. Suppression was a dose dependent phenomenon and dose of 28mg/kg and 40mg/kg given intraperitoneally five though 14 days postinoculation gave significant protection. Perivascular inflammation in the central nervous system was also suppressed in animals receiving effective doses. Although these doses were well tolerated, cytoplasmic lamellar-bodies were found in the central nervous system of all SG treated animals. Also, animals treated with SG developed diarrhea and weight loss, although histologic study of the gastrointestinal tract revealed no lesions.

Source: J. of Neuropathol. Exp. Neurol., 1987, 46(3), 250~261.

2. 스피로 게르마늄의 항관절염과 면역조절 활성 (약학과 실험 치료학)

Antiarthritis and immunoregulatory of spirogermanium
M. J. Dimartino, J. C. Lee, A. M. Badger, K. A. Murhead, C. K. Mirabelli and N. Hanna
Smith Kline & French Labotories

Abstract

Spirogermanium is novel metal containing azaspirane compound with reported antitumor activity. The results of the present investigation demonstrate that spirogermanium also exhibits antiarthritis and immunoregulatory activities after p.o. administration to rats. Spirogermanium decreased hind leg inflammatory lesions of adjuvant arthritic rat when administered p.o. before or after the development of the arthritic lesions. After termination of spirogermanium administration, the adjuvant injected hind leg lesions remained significantly suppressed for at least 2 weeks post-drug treatment; whereas, the uninjected, immune-mediated hind leg inflammation tended to increase postdrug treatment. In multiparameter ex vivo studies, untreated arthritic rats exhibited enhanced cyanine dye fluorescence in peripheral blood monocytes, enhanced interleukin (IL)-1 production by adherent spleen cells and depressed IL-2 and IL-3 production by splenic lymphocytes. Spirogermanium normalized these changes to various degrees, with the exception of the depressed IL-2 and IL-3 production. Spirogermanium administered to normal nonarthritic rats decreased mitogenic responses of spleen cellc to Concanavalin A which was found to be caused, at least in part, by enhanced suppressor cell activity. The antiarthritic and immuno-regulatory profile of spirogermanium appeared to be different from the profiles of the antiarthritic agents, auranofin and indo-methacin.

Source: J. Pharma. & Exp. Thera. 1985. 236(1) 

면 역 활 성

1.면역부활제에 의한 인터페론 유도와 NK세포 활성증강 작용 (의학의 흐름)

Interferon induction and augmentation of NK cell activity by immunopotentiators
Abstract

Seven kinds of immunopotentiators including organic germanium can induce the interferon secretion in some cancer patients and patients with infectious viral diseases. Also, they can augmentation of Natural Killer (NK) cell’s activities including non-specific, but systematic immuno-enhancement against endogenous cancer cells and virus infected cells. Therefore it can be used as a natural drug for cancer treatment and viral disease.

Source: Current Medicine. 1956. 117(5)

2.Ge-132가 시험관에서 인체 NK세포활성에 미치는 영향 (의학과 생물학)

Effects in vitro of Ge-132 on the activity of human natural killer cells.
Miyoko Yoshida and Shigeru Arimori.
The fourth Department of Internal Medicine, School of Medicine, Tokai University.
 

Abstract

Organo germanium, Ge-132, have been known to have a variety of biological activities including immuno-enhancement and anticancer activities. In this study, we evaluate of activation of NK cells in vitro by organic germanium. In the results, organic germanium has been shown activation of NK cell’s activities. For elucidate more precise mechanism, further study needed since activity of NK cell were depend on germanium concentration, reaction temperature, and time.
 

Source: Medicine and Biology. 1982. 104(2), 87~89.

3.비글개에 있어서 Ge-132에 의한 NK세포 활성증강에 관하여 (의학과 약학)

Effects of Germanium on the activity of NK cells in Beagle dog

Abstract

Germanium is present in all-living plant and animal matter in micro-trace quantities. Its therapeutic attributes include immuno-enhancement, oxygen enrichment, free radical scavenging, analgesia, and heavy metal detoxification. In this study, clinical effect of Germanium on augmentation of canine NK cell activity in normal and tumor bearing beagle dog. In the results, organic germanium can activate NK cells significantly in tumor bearing dog compared with in normal dog. It would be due to induced interferon by germanium. 

Source: Medicine and Pharmacology. 1983. 10(5), 1659~1661.

4.카드뮴, 아연, 및 유기게르마늄이 일차면역 반응에 미치는 영향에 관한 연구 (연대 의학과)

Studies on effect of Cadmium, Zinc and Organic germanium in primary immune response
Tae-Suk, Cha
YonSei Univ. Dept. of Medicine

Abstract

The precise action mechanisms of heavy metal in human body are not clear. Especially the relationship between disease occurrence from long term exposed population and several heavy metals are needed to further studies. However, cadmium compounds and zinc compounds have been known immuno-enhancement or immuno modulating agents depend on their inoculation methods or dosage. Furthermore, organic germanium has been known as potent activator of immunity. In these regards, in this study, the effects of several heavy metals including cadmium, zinc, and organic germanium in primary immunity through comparison of immune responses, notify the changes in histochemical and serological aspects, and synergistic or antagonistic effects between them. Also, the germanium effect on the heavy metal was elucidated. 

5.유기게르마늄의 경구투여한 쥐에서 인터페론의 유도와 NK세포, 마크로파지의 활성화 (미생물 면역학)

Induction of interferon and activation of NK cells and macrophages in mice by oral administration of an organic germanium compound Hisashi Aso, Fujio Suzuki, Takahiro Yamaguchi, Yoshiro Hayashi.
Takusaburo Ebina, and Nakao Ishida

Department of Bacteriology, School of Medicine, Tohoku University

Abstract

After oral administration of an organic germanium compound, Ge-132 (300mg/kg), a significant level of interferon (IFN) activity was detected in the sera of mice at 20 hr and it reached a maximum of 320 U/ml at 24 hr. This IFN activity was lost after heat- or acid-treatment, suggesting that the induced IFN be of g -nature. The molecular weight of this IFN was estimated to be 50,000 daltons by gel filtration. The NK activity of spleen cell was increased 24 hr after the oral administration of Ge-132, and cytotoxic macrophages were induced in the peritoneal cavity by 48 hr. In the mice receiving an intraperitoneal (ip) injection of trypan blue or carrageenan 2days before oral administration of Ge-132, neither induction of IFN nor augmentation of NK activity occurred, and X-ray irradiation of mice also rendered the mice incapable of producing IFN, all indicating that both macrophages and lymphocytes are required for this IFN induction. Both NK and cytotoxic macrophages appeared 18 hr after ip administration of the induced IFN with a titer as low as 20 U/ml. These facts suggested that both the augmentation of NK cell activity and activation of macrophages in mice after oral administration of Ge-132 are mediated by the induced IFN.

Source: Microbiol Immunol. 1985, 29(1), 65~74

 
6.유기게르마늄 화합물 투여에 의한 2-5A 합성효소의 유도 (의학과 약학)

Induction of 2-5A synthetic enzyme by organic germanium administration

Abstract

Interferon is widely used as anti-viral infection and anti-tumor in human body. The effects small quantity of interferon on the human body was not clearly elucidated, but they affect on systemic and effectively. In the previous studies, both the augmentation of NK cell activity and activation of macrophages in mice after oral administration of Ge-132 are mediated by the induced IFN. These activation was mainly due to induced interferon by germanium. Germanium can inducing interferon secretion by activated or increased specific enzyme, 2-5A synthetase. It suggested that increased interferon was due to activated 2-5A synthetase and these activated enzyme activity achieved through germanium effects.
Source: Medicine and Pharmacology. 1987. 17(6). 1523~1528.

7.인터페론 및 인터페론 유도제에 관한 기초적, 임상적 연구 (오까야마의학지)

Experimental and Clinical studies on interferon and its inducers Mitsuhiro Fukumoto
Second Dept. of Internal Medicine, Okayama University.

Abstract

To evaluate one of the effects of interferon and its inducers on neutrophil functions, neutrophil chemiluminescence (ChL) was assayed on 31 healthy individuals, nine patients treated with IFN-alpha and 11 patients treated with Ge-132. The base lines (BLs), peak levels (PLs) and time to PLs (PTs) of neutrophil ChL were examined before, one week and one month after the treatment. The direct effects of IFN-alpha, Ge-132 and OK-432 on neutrophil ChL were also evaluated by using an in vitro experimentl system. PLs were significantly increased one week after the treatment with IFN-alpha or Ge-132. However, they were decreased to the pretreatment level one month after the treatment. In vitro experimental system IFN-alpha enhanced PLs of neutrophil ChL showing dose and time dependencies. One the other hand Ge-132 and OK-432 showed no direct effect on neutrophil ChL in vitro. These finding suggest that IFN-alpha and Ge-132 enhance the host defense mechanism by the activation of neutrophil functions, and also suggest that they have some benefits not only in the clinical management of cancer but also of chronic infection.

Source: J. Okayama Medicine. 1992. 104, 259~266.

8.게르마늄이 대식세포의 활성화에 미치는 영향 (전북대 의학과)

Effect of germanium on the macrophage activation Myung Soo, Oh
Department of Medicine, Chunbuk National University.

Abstract

Organic germanium compounds have been known to have a variety of biological activities including antiviral and antitumor activities. Ge-132, one of organic germanium compounds was found to induce macrophage activation. In this study, the macrophage activation by in vivo and in vitro treatment of Ge-132 was confirmed by the measurement of the nitric oxide production and decreased of NAD glycohydrolase activity, which are the indicators of macrophage activation. And also, the mechanism of the macrophage activation by Ge-132 was analyzed by lymphocyte / macrophage mixed cultures. Organic germanium induced lymphocytes to produce interferon-gamma and tumor necrosis factor (TNF)-alpha, thereby indirectly activated macrophages.

Source: Chunbuk Nat’l Univ. Dept. of Medicine. 1997.

백 내 장

1. 게르마늄-132의 백내자에 대한 효과 (눈연구 동향)

Effect of pretreatment of germanium-132 on Na+-K+-ATPase and galactose cataracts Nalin J. Unakar, Jane Tsui and Margaret Johnson Department of Biological Sciences, Oakland University, USA

Abstract

Purpose. Recently, we reported that topical administration of 2-carboxyethyl germanium sesquioxide (Ge-132) concurrently with 50% galactose feeding delayed the establishment of mature cataracts and reduced advance glycation product. This study was to determine the effect of pretreatment of Ge-132 on galactose associated morphological changes and Na+-K+-ATPase activity.

Methods. Young Sprague Dawley rats received topical eye drops four times a day of either saline or Ge-132 seven days prior to the 50% galactose diet and during galactose feeding. At desired intervals the lenses were extracted, photographed and processed for either light microscopy, scanning electron microscopy or the determination of Na+-K+-ATPase activity.

Results. In Ge-132 pretreated lenses as compared to saline pretreated lenses the following results were observed: (a) the galactose-induced morphological alterations in the majority of lenses were delayed and (b) Na+-K+-ATPase activity was protected.

Conclusions. Our previous and current studies show that in addition to osmotic stress post-translational protein modification, such as glycation, including enzymes may play a role in initiating changes that lead to cataract development. The inhibition of protein glycation by antiglycating compounds, such as Ge-132, delays sugar cataract formation. Currently, we are investigating the status of protein glycation and advanced glycation end products following pretreatment with Ge-132 and the role of Ge-132 on the activities of enzymes such as aldose reductase and Na+-K+-ATPase. 

Source: Current Eye Research. 1997. 16, 832~837.

산 소 공 급

1. 초건강을 위한 산소-영양소 (정분자의학)

Journal of Orthmolecular Medicine.1986. 1(3),145~149. Oxygen-Nutrition for Super Health
Research Breakthrough on an Oxygen Catalyst Stephen A. Levine and Parris M. Kidd

We wish to introduce an exciting new orthomolecular concept - Oxygen-Nutrition for Super Health. It's becoming clear from research findings in oxygen biochemistry, that correct tissue oxygenation and in addition a correct food/oxygen mixture is absolutely required for optimal health. Breathing provides the spark for life; nutrition keeps the fire burning. In our everyday activity, in exercising and endurance training, and in response to life's stresses, oxygenation of our tissues is often the factor which most limits our performance. We suggest that for optimal health, the individual needs to consider not only optimizing nutrition but optimizing oxygenation in order to optimally utilize one's foods.

Oxygen and Human Survival

Oxygen is the single substance upon which our life is most dependent. Without oxygen we survive for 4-5 minutes at most. The paramount importance of oxygen for human health is well-illustrated by the findings that, of all the parameters associated with long life, respiratory capacity is the number one parameter, rating over cigarette smoking and blood cholesterol levels (1).

To better illustrate the function which oxygen has in the human body, we might make a limited analogy between our living metabolism and the engine of an automobile. Both require finely tuned car-buretion (fuel/oxygen mixing) for smooth "burn" and maximum power. In modern technological societies we tend to indulge ourselves with an over-rich fuel mixture: too much fuel, too little oxygen. Due to lack of information, poor understanding, or lack of motivation, many of us do not exercise sufficiently to get enough oxygen. Adequate cellular and tissue oxygenation is essential for us to efficiently extract energy from our foods and to "air out" our body tissues. The latter process is essential for health, due to the tendency of acidic byproducts resulting from suboptimal oxygenation (such as lactic acid) to accumulate in poorly-oxygenated tissues. These byproducts are familiar as the predominant cause of muscle cramps during exercise by the overtired or underfit.

Oxygen, Life Stressors, and Cancer

Not only is oxygen necessary for using our foods efficiently, but the consumption of certain foods actually tends to deplete our oxygen supplies. Many of the highly toxic environmental pollutant chemicals such as pesticides, herbicides, solvents, and diverse other petroleum byproducts are largely fat-soluble and come to reside in our high-fat tissues (2). As we consume a high-fat meal, we're very likely also consuming high amounts of environmental toxins. Whether obtained through direct exposure (occupational, household, happenstance), or through contaminated foods, these toxins are invariably peroxidative, consuming oxygen as they attack our cellular membranes (3,4). Their presence in our bodies also requires that we utilize oxygen in our attempts to detoxify them via the “P450” Enzyme System (4).

The Oxygen-Nutrition concept emphasizes lifestyle factors as they affect oxygen utilization. A diverse variety of stressful life occurrences, whether they be toxic chemical exposures, exposures to infectious agents, excessive emotional stress, overexercise, or physical injury, result in free radical generation in our tissues, concomitant with local depletion of oxygen from free radical-initiated lipid peroxidation (3). A free radical is a highly reactive molecular fragment which poses a destructive threat to biological molecules. If the stressor source cannot be reduced, it is likely that peroxidative processes will eventually bring on abnormal lowering of tissue oxygen (hypoxia) which then predisposes the affected person to any of the degenerative illnesses so prevalent in civilized countries today (7).

Cancer, possibly the most feared disease today, may develop in an environment of oxygen starvation (5). Cancer cells seem to thrive in hypoxic environments. Indeed, we find from the cancer literature that cancer cells have effectively lost the ability to utilize oxygen (6). They've apparently reverted to a form of ancestral existence which doesn't require oxygen, much resembling anaerobic metabolism (glycolysis). Such metabolic characteristics would fit them well to survive and proliferate in low-oxygen environments. This we believe reflects the ultimate stage of cellular degeneration attributable to “low-oxygen lifestyle”.

Oxygen, Immune Function, and Candida Overgrowth

One major life stressor is infection. Our immune system protects us against infectious agents (“pathogens”) such as viruses, bacteria, and fungi. The immune system requires adequate-supplies of oxygen, since the immune "bug destroyers” (the phagocyte cells) use oxygen to produce help them to sense, intercept, attack and kill pathogens (7). The paradox for our phagocyte “security force” is that these very cells are themselves vulnerable to damage from their own free radical products. Phagocytes must therefore have adequate supplies of oxygen, as well as particularly powerful antioxidant protection. Even those immune cells which are not capable of phagocytosis, such as the T lymphocytes which kill cancer cells, also appear to rely on oxygen free radicals. Selective oxygen-free radical production to kill “non-self” cells, concomitant with optimal antioxidant status to defend the self cells is, we believe, the fundamental basis of “cell-mediated” immunity. Hence our critical dependence on optimal Oxygen-Nutrition for optimizing our resistance to disease.

Poor Oxygen-Nutrition may underlie the current epidemic of Candida (fungal yeast) overgrowth in our society, a condition which requires impaired immune defense. As many as 30 percent of Americans may be affected. Dr. Orion Truss has suggested that Candida overgrowth develops during stressful periods or as a result of other life events which lower our immune potential (8). Candida is commonly associated with food and chemical hypersensitivity, as well as with many other common illnesses. Candida overgrowth can underlie common gastro-intestinal and genito-urinary tract conditions such as indigestion, heart-burn, bloating, cystitis, anal itching, vaginitis, asthma, hives, acne, hay fever, bronchitis, earaches and mental and emotional problems including headache, extreme irritability, confusion, depression, memory lapses, and lethargy. Immune phagocytic activity appears to be the major factor in limiting the spread of infection by opportunistic fungi such as Candida (9). It is believed that the process of attachment of the fungal hyphae to host cells activates the oxidative metabolism of the phagocytes, setting their lethal “respiratory burst” into motion. This “respiratory burst” is a surge in oxygen consumption by the cells, which then use the extra oxygen to generate free radicals aimed at destroying unwelcome pathogens. Cell-mediated immunity therefore depends critically on having sufficient oxygen in our blood and hard tissues.

Oxygen Fine-Tuning by Germanium

In relationship to cellular oxygenation the element germanium appears to play a (newly-discovered) critical role. Germanium (Ge), atomic number 32, atomic weight 72.6, tends to form a lattice-like structure and is a superb electron conductor (semiconductor). Whereas in the ‘50s and ‘60s it had become generally accepted that germanium had little biological significance, more recently Ge has attained new prominence from research and clinical findings centered around the work of Asai and summarized in his book “Miracle Cure: Organic Germanium” (10).

Concentrations of Ge in foods and other biomaterials mostly range from 0.1 to 1.0 ppm; hence one might expect to find from 0.1 to 1.0 micrograms of germanium per gram of food material. However, the amounts of germanium in medicinal plants were reported by Asai to attain Ge levels as high as 2000 ppm. Shelf fungus, for long regarded as an effective treatment for cancer, currently tops the list at 800-2000 ppm. Garlic was measured at 754 ppm, and aloe and chlorella at more than 70 ppm (11). Since this report by the late Dr. Asai first appeared, there has been a surge of interest in the possible nutritional and pharmacological importance of germanium.

Acute and chronic toxicity studies conducted by Asai have indicated that germanium is essentially nontoxic (10,18). Additional studies utilized “Ge-132” (carboxyethyl germanium sesquioxide/Organic Germanium), originally synthesized by the Asai Germanium Research Institute in Tokyo, Japan.* Organic Germaniuni/Ge-132 was shown to have extremely low toxicity in test animals, up to an equivalent in humans of many grams per day.

The clinical trials at Dr. Asai’s Germanium clinic produced results that were impressive, even though they were not controlled studies. Numerous case histories, along with standard blood chemistry parameters, were taken of patients with a broad ranging spectrum of symptomatologies (12). Under medical supervision at the Organic Germanium Clinic in Japan, hepatic dysfunction, hepatitis, and various cancers including leukemias were just a few of the serious diseases that responded well to Organic Germanium at doses ranging from 50 to 1000 mg per day. Diseases of the eye, including cataracts, often responded quickly and dramatically. Organic Ge produced excellent results when used on hypertensive patients, and was surprisingly effective at modulating blood pressure in SHR (spontaneously hypertensive) rats. Patients with myocardial infarction, angina pectoris and Raynaud’s disease responded well to dosages as high as 1400 mg per day. Astonishing benefits were reported against mercury, cadmium, and other metal poisons (10).

Organic Germanium Stimulates Immunity

Organic Ge is a dramatic inmunostimulant. In controlled studies it has demonstrated marked anti-tumor effects and interferon-inducing activity, and restored immune function in immune-depressed, aged mice (13). These immunostimulating effects were achieved with oral dosages, and no harmful side effects were noted. Also, there are reports describing its enhancement of natural killer cell activity in healthy human subjects (14). Studies on immune-suppressed animals and on patients with malignancies or rheumatoid arthritis suggested that Organic Ge normalized the function of T cells, B lymphocytes, antibody-dependent cellular cytotoxicity, natural killer cell activity and numbers of antibody-forming cells (13). Anti-tumor effects from Ge-132 were reported in mice with Lewis lung carcinoma, chemically-induced sarcoma, and leukemias (16). Evidently Organic Germanium has a profoundly positive influence on the immune system (15).

Germanium also reportedly has analgesic properties. The painkilling effect of Asai’s Organic Germanium were first recognized during its early clinical use and confirmed from further studies. Taken orally or by intravenous injection, it clearly enhanced morphine-induced analgesia. It was suggested that Organic Ge may activate dopaminergic or serotoninergic neurons in analgesic pathways and/or trigger release of endogenous enkaphalins or endorphins (17).

Conclusion: Oxygen-Nutrition and Germanium

The apparent versatility of Organic Germanium in normalizing health and alleviating major human diseases and dysfunctions suggests that it acts at a fundamental level of life function. The known biological and clinical effects of Organic Germanium are consistent with Dr. Asai’s suggestion that it can (at least partially) substitute for or supplement oxygenation in our tissues. It could facilitate energy generation from high-energy electrons, akin to the well-understood role of oxygen as an “electron sink” essential for energy-yielding electron transfer processes. In those cells which cannot utilize oxygen, i.e. cancer cells which actually are oxygen-sensitive we might predict that its presence as an “oxygen-catalyst” could have therapeutic consequences.

The discovery of the biologic value of germanium sesquioxide, Asai’s “organic germanium compound” is a landmark development in the field of nutritional medicine. This breakthrough stems from Asai’s initial finding that Ge occurs in such high concentrations in medicinal plants. It appears that Asai has identified one of the main active principles accounting for the therapeutic action of many old-age remedies. The late Dr. Asai did not regard germanium as a drug. He stated “I would rather call it a health-giving substance it restores health to those afflicted with disease, and sustains health in those who are healthy.”

Bibliography

Cullen, K. et al.: Multiple regression analysis of risk factors for cardiovascular disease and cancer mortality in Busselton, Western Australia - 13 year study. J. Chron. Dis. 36:371-377, 1983. 
Laseter, J. L., DeLeon, I. R., Rea, W. J. and Butler, J. R.: Chlorinated hydrocarbon pesticides in environmentally sensitive patients. Clin. Ecol. 2, 3-12, 1983. 
    
3. Levine, S. and Kidd, P.: Antioxidant Adaptation: Its Role in Free Radical Pathology. Biocurrents                                           Division, Allergy Resech Group, 400 Preda St., San Leandro, CA 94577, 1985.

    4. Ibid: Chapter 7.

    5. Levine, S. and Kidd, P.: Beyond antioxidant adaptation: a free radical-hypoxia-clonal thesis of 

         cancer causation. J. Orthomol. Psychiatry. 14(3):189-213, 1985.

   6. Oberley, L. W.: Superoxide dismutase and cancer. In: Superoxide Dismutase (Vol II), 127-

        166 (Chapter 6). Ed. by L. W. Oberley. Boca Raton, Florida: CRC Press, 1982.

   7. Levine, S. and Kidd, P. Antioxidant Adaptation, Chap. 5, 1985.

   8. Truss, O. C.: Metabolic abnormalities in patients with chronic candidiasis: the acetaldehyde 

       hypothesis J. of Orthomolecular Psychiatry, Vol. 13, No. 2, 1984.

   9. Levine, S. A.: Candida albicans and oxygen-free radical processes. International Journal of 

                             Holistic Health, Fall, 1985.

   10. Asai, K.: Miracle Core: Organic Gamanium. New York: Kodansha International Harper &  Row, 1980.

   11. Ibid. p. 22; Asai, K., 1973. Shoku No Kagaku, 12:81 (in Japanese); but see also Mino et at, 1980.                             Determination of germanium in medicinal plants by atomic absorption spectrometry                             with electrothermal atomization. Jap.  Pharm. Bull. 28:2687-2691.

   12. Asai, K.: Miracle Cure, pp. 99-131.

   13. Mizushima, Y. et al.: Restoration of impaired immunoresponse by germanium in mice. Int. Archs.         Allergy Appl. Immune. 63:338-339, 1980; Suzuki, F. and Pollard R. B., 1984. Prevention of         suppressed gammainterferon 
        production in thermally injured mice by administration of a novel organo-germanium compound,        Ge-132. J. of  Interferon Research, 4:223-233; Aso H., et. al., 1985. Induction of interferon and        activation of NK cells and  macrophages in mice by oral administrations of Ge-132, an organic        germanium compound. Microbial. Immunol.  29(l):65-74.

    14. Yoshida, M. and Arimori, S.: Effects of Ge-132 in vitro on the activity of human natural killer cells.           Med, Biol.  104:87-89 (in Japanese); 1982; Arimori S., et. al., 1981. In: lmmunomodulation by          Microbial Products and  Related Synthetic Compounds. Y. Yamamura et al. (eds.) Elsevier Science          Publishing: Amsterdam, Holland, pp. 498-500.

    15. Asai Germanium Res. Inst., 1984. Ge-132 outline. (Unpublished)

    16. Kumano, N. et al.: Antitumor effect of the organogermium compound Ge-132 on the Lewis Lung          carcinoma  (3LL) in C57BL/6(B6) mice. Tohoku J. Exp. Med., 146:97-104, 1985.

    17. Hachisu, M. et al.: Analgesic effect of novel organogermanium compound, Ge-132. J.          Pharm.Dyn.6:814- 820,1983.

    18. Aso, H. et al.: Microbiol. Immunol. 29(l):65-74, 1985.
 

 

 

 

 

암 발 생 억 제

1. 일부 필수 미량원소 결핍의 결과로서의 발암현상 (의학적 학설)

Carcinogenesis as the result of the deficiency of some essential trace elements Boleslaw Marczynski  Dept. of Biochemistry, Silesian University, Poland

Abstract

“Energetic” biological trace elements [gallium (III), germanium (IV), silicon (silica), arsenic (V) and selenium (IV)] occurring in DNA of eukaryotic cells may improve the semiconductor properties of DNA and may influence the mechanisms that control genetic expression at the electronic level. Their roles are postulated as follows: (i) to maintain the level and direction of free sliding electrons in DNA, (ii) to modulate the electron conductivity and hole conductivity of DNA. This specific electronic nature of DNA take the form of magnetic pigeonholes in which an electric pulse is (0), or is not (1) stored as an area of local magnetisation. These types of conductivity occurring in different parts of DNA of different cells could participate in the switch on and switch off of genetic information in gene expression. This model may help to elucidate the mechanism of action of these naturally occurring antitumor agents and may help in understanding the role of trace elements in charge transport of DNA and in carcinogenesis. 
Source: Medical Hypotheses. 1988. 26, 239~249.
 

2. 디에틸니트로사민에 의해 발생되는 쥐 간암 발생에 있어서 알릴설피드, 게르마늄과 NaCl의 영향 (항암연구)

Effects of allyl sulfide, germanium and NaCl on the development of glutathione S-transferase P-positive rat hepatic foci initiated by diethylnitrosamine Ja June Jang, Kyung Ja Cho and Sung Ho Kim. Dept. of Anatom. Pathol. and Lab. of Cancer Pathol., Korea Cancer Center Hospital
 
Abstract

The modification potentials of allyl sulfide, germanium and NaCl on the development of preneoplastic hepatic enzyme altered foci were examined in vivo mid-term assay system. Rats were initially given a single dose (200mg/kg), intraperitoneal injection of diethylnitrosamine (DEN) and, starting 2 weeks later, were treated with allyl sulfide, germanium and NaCl at a concentration of 0.5%, 0.05%, 5%, respectively, in the diet for 6 weeks and then killed. All rats were subjected to two-thirds partial hepatectomy at week 3. The modifying potential was scored by comparing the number and area per cm2 of induced glutathione S-transferase placental form-positive (GST-P+) foci in the liver with those of the corresponding control group given DEN alone. Allyl sulfide exerted an obvious inhibition of the development of GST-P+ foci as regards both number and area. On the contrary, germanium showed significant increase in the number of GST-P+ foci, although the data for area were not altered. NaCl had no modifying effects on their development.
Source: Anticancer Research. 1989. 9, 273~276.

3. 쥐의 다기관 발암현상 모델에서 알릴 설피드, 인돌-3-카비놀과 게르마늄의 변형작용 (발암현상)

Modifying responses of allyl sulfide, indole-3-carbinol and germanium in a rat multi-organ carcinogenesis model   Ja June Jang, Kyung Ja Cho and Sung Ho Kim. Dept. of Anatom. Pathol. and Lab. of Cancer Pathol., Korea Cancer Center Hospital

Abstract

The modification potentials of allyl sulfide (AS), indole-3-carbinol (I3C) and carboxyethylgermanium sesquioxide (GE) on lesion development was examined in a wide-spectrum initiation model. Groups 1-4 were treated sequentially with diethylnitrosamine (DEN), N-methyl-nitrosourea (MNU), and N, N-dibutylnitrosamine (DBN). Groups 5-7 received vehicles without carcinogens during the initiation period. Group 8 served as the untreated control. After this initiating procedure, groups 2-7 were administered a diet containing 0.5% AS or I3C and 0.05% GE. All surviving animals were killed 40 weeks after the beginning of the experiment and the target organs were examined. The induction of GST-P+ hepatic foci in rat treated with carcinogens was significantly inhibited by the treatment with all three compounds. As treatment significantly decreased the incidence of the hepatic hyperplastic nodules, adenoma of the lung and thyroid, and papillary or nodular hyperplasia of the urinary bladder. Administration of GE also significantly inhibited the development of hepatic nodules and adenoma of the lung and thyroid. However, I3C only inhibited the hyperplastic nodules of the liver. These results demonstrated that this multi organ initiation model could be useful in confirming organ specific modification potential and, in addition, the inhibitory effect of AS, I3C and GE on liver, lung, thyroid and urinary bladder carcinogenesis.

Source: Carcinogenesis. 1991. 12(4), 691~695. 

약 리 효 과

1. 유기게르마늄의 치료효능 (의학적학설)

Therapeutic effects of Organic Germanium Dr. Sandra Goodman,International Inst. Of Symbiotic Studies 5. Fairlight Place, Brighton, Sussex U. K.

Abstract

Germanium is present in all-living plant and animal matter in micro-trace quantities. Its therapeutic attributes include immuno-enhancement, oxygen enrichment, free radical scavenging, analgesia, and heavy metal detoxification. Toxicological studies document Germanium’s rapid absorption and elimination from the body, and its safety. Clinical trials and use in private practices for more than a decade have demonstrated Germanium’s efficacy in treating a wide range of serious afflictions, including cancer, arthritis, and senile osteoporosis. Germanium’s anti-viral and immunological properties, including the induction of interferon, macrophages, T-suppressor cells and augmentation of natural killer cell activity, suggest its possible efficacy in treating and/or preventing AIDS. 

Source: Medical Hypotheses (1988) 26, 207~215

2. 식물성 게르마늄화합물에 관하여 (와다나베)

Studies on germanium compound from plant Watanabe

Abstract

Germanium is one of trace element in all living matters. In oriental countries including China, Korea, and Japan, oriental herbs including Korea Ginseng, Garlic, some mushrooms were used for treating disease and for augmentation of health. They have concentrated germanium as bounded with organic acids than other living things. However, there are no or little organic germanium in artificial cultured them. Accordingly, effectiveness as a medicine would be decided by quantities of organic germanium. They can act as an inducer of interferon secretion and a blocking agent from various oxygen radicals and heavy metals. It would be important in anti-aging and anticancer properties as one of the medicine.
 
3. 게르마늄 화합물의 일반약리작용에 관한 연구 (응용약리)

Studies on general pharmacological effects of some germanium compounds
Setsuo Tomizawa, Nobuo Suguro, and Masatoyo Kagoshima.
School of Pharmaceutical Sciences, Kaitasato University, Tokyo

Abstract

The general pharmacological effects of germanium dioxide (GeO2), β-carbamoylethyl germanium sesquioxide (germano propionly amide, GeA) and β-carboxyethyl germanium sesquioxide (germano propionic acid, GeP) were studied. In mice, the LD50 after intraperitoneal administration was 1550mg/kg for GeO2, 7100mg/kg for GeA and 2820mg/kg for GeP, respectively. But multidimensional observation, GeO2 exhibited mainly inhibitory effects, while GeA and GeP showed at first excitatory followed by inhibitory effects in their toxic doses. The three compounds had analgesic action, but GeO2 and GeA prolonged the sleeping time caused by hexobarbital-Na in mice. Neither local anesthetic nor mucous stimulating action was observed in these three compounds. GeP showed hemolytic action in its relatively low concentrations, although the others had no such action. In rabbit, they did not have any predictable effects on the respiration, on the blood pressure and on the urinary amounts in doses of up to 10mg/kg by intravenous injection. GeO2 had no marked effected on the isolated rabbit ear vessels, but GeA had the tendency to be vasodilatory and, on the contrary, GeP to be vasocontrictory in their large doses. In higher concentrations, the automaticity of the isolated frog heart was inhibited by them. In higher concentrations, the automaticity of the isolated rabbit ileum was excited by GeO2 and GeP, but inhibited by GeA. Also, in higher concentrations, the automaticity of the isolated rabbit uterus was excited by GeA and GeP, while GeO2 had no remarkable effects on it.

 Source: Applied Pharmacology (1978) 16 (4), 671~682

4. 유기게르마늄 화합물인 Ge-132의 약리활성 (의학과 약학)

Pharmacological activity of organic Germanium

Abstract

Organo germanium, Ge-132, have been known to have a variety of biological activities including immuno-enhancement and anticancer activities. They have anticancer activities through increasing interferon secretion, macrophage activation, NK cell activation, increasing cellular immunity, increasing the antigen dependent cytotoxic cell (ADCC), and activation of cytotoxic T cells. These phenomenons were due to interferon secretion by organic germanium. Furthermore, it can be used for recovery and maintaining calcium metabolism, analgesic drug for chronic patients, and maintaining the homeostasis of body.

Source: Medicine and Pharmacology. (1983) 9(3), 814~826

     통

1. 엔케팔린 분해효소 유도에서 Ge-132의 통각억제 효과 (생명과학과 응용 생화학)

Mutagenicity, Carcinogenicity and Teratogenicity of Germanium Compounds G.B. Gerber, A. Leonard
Teratogenicity and Mutagenicity Unit, Catholic University of Lourain, Belgium

Abstract

The metalloid germanium has found widespread application in electronics, nuclear sciences and medicine. General toxicity of germanium is low, except for the tetrahydride germane, and few observations on toxicity of germanium in man exist. Germanium is not carcinogenic and even appears to inhibit cancer development and, in the form of the organic germanium compound, spirogermanium, to destroy cancer cells. Germanium compounds have no mutagenic activity and may, under certain conditions, inhibit the mutagenic activity of other substances. High doses of germanium may result in an increased embryonic resorption, but possible malformations have been reported only after administration of dimethyl germanium oxide to pregnant animals. Germanium may thus be considered an element of rather low risk to man.

Source: Mutation Research. 1997. 387, 141~146.

콜 레 스 테 롤  저 하

1. 13가지 미량원소를 먹인 쥐에서 혈중 콜레스테롤 수치 (식량학회)

Serum Cholesterol Levels in Rats Fed Thirteen Trace Elements  HENRY A. SCHROEDER
Department of Physiology, Dartmouth Medical School, and Brattleboro Memorial Hospital

Abstract

To ascertain differences in serum cholesterol levels as possibly affected by trace elements in the drinking water, rats were given soluble salts of zirconium, vanadium, niobium, chromium, nickel, cadmium, germanium, tin, lead, arsenic, and antimony at 5 ppm and selenium and tellurium at 2 ppm from the time of weaning until 11 to 30 months of age. The feeding of chromium at 1 ppm was associated with suppressed levels in males but not in females; 5 ppm appeared to be required for this effect in females. The lowest serum cholesterol levels were observed in groups given germanium, niobium, chromium and nickel, the highest in groups fed tellurium, with all animals receiving I ppm chromium. Significant differences in values of the 2 sexes appeared for 7 elements. It is possible that chromium, nickel and niobium exert anti-cholesterogenic properties, whereas tellurium may be cholesterogenic.

Source: J. Nutrition. 1968. 94.

항 바 이 러 스 효 과

1. 유기게르마늄 화합물 Ge-132의 백시니아 바이러스 감염억제 작용

Suppressive effect of organic germanium on Vaccinia virus infection Iwao Umezawa and Kanki Komiyama. The Kitasato Institute

Abstract

Ge-132 is one of potent biological response modifier (BRM) in human through activation of immunity. Induction of interferon and activation of NK cells and macrophages were achieved by administration of germanium. In this study, antiviral activity, one of another potent activities of organic germanium was investigated. The antiviral activity was measured by counting the plaque forming units (pfu) in each time. The pfu counting was minimal in the highest Ge-132 group at various treating times than control group when the DDY mice were infected with vaccina virus. It is clearly showed that Ge-132 can protect from vaccinia virus infection and propagation in mice. In other studies, induction of interferon and activation of NK cells and macrophages were achieved by administration of germanium. The propagation of virus was inhibited by germanium through activation of host’s immunity.

Source: Medicine and Biology. 1987. 114(6), 393~395.

항 산 화 작 용

1. 낮은 농도의 셀레늄 함유 곡물을 먹인 쥐에서 셀레늄, 게르마늄이 지질과산화에 미치는 영향 
    (중국예방의학회지) 

Effects of selenium and germanium on lipid peroxidation in rats fed with low-selenium grain
 Xie Wen, Chen Xuemin, Yang Kedi et al Dept. of Environmental Health Tongji Medical University

Abstract

Rats were fed with grain produced in the area prevalent of Keshan disease for 12 weeks, by adding certain amount of sodium selenite (Na2SeO3) and carboxyethyl germanium (Ge-132) to study the combined effects of selenium and germanium on lipid peroxidation and metabolism of free radicals in their bodies. Results showed selenium and germanium added to the grain could reduce the content of free radicals in rats liver and kidney tissues, and that of lipid peroxide in their heart, liver and kidney, and increase the activation of glutathione peroxidase (GSH-Px) in their blood, in a synergic way. 

Source: Chin. J. Prev. Med. 1996. 30(2)

 
 

 

 

 

 

 항 암 효 과

1. Ge-132에 의한 L1210 백혈병세포의 열발생 (의학과 생물학)

Heat production from L1210 leukemic cells by carboxyethyl-germanium sesquioxide, Ge-132
Shigeru Arimori and Shunji Takeuchi
Department of Internal Medicine, School of Medicine, Tokai University

Abstract

Carboxyethyl-germanium sesquioxide, Ge-132, have been known to have a variety of biological activities including immuno-enhancement and anticancer activities. These facts suggested that both the augmentation of NK cell activity and activation of macrophages after oral administration of Ge-132 are mediated by the induced IFN. Accordingly, they have some benefits not only in the clinical management of cancer but also of chronic infection. Also, it may be useful as an inducer of contrasuppressor T cells in immunocompromised individuals bearing suppressor T cells. In this study, we evaluate heat production measured with a flow microcalorimeter in leukemic cell treated with Ge-132. In the results, heat production from leukemic cell by germanium was increased dose dependent manner. 

Source: Medicine and Biology

2. Ge-132를 처리한 L1210 세포의 전자현미경 관찰 (의학과 생물학)

Election microscopic observations of L 1210 cells treated in vitro with Germanium-132
Shigeru Arimori and Shunji Takeuchi
Dept. of Medicine, Tokai University

Abstract

Carboxyethyl-germanium sesquioxide, Ge-132, have been known to have a variety of biological activities including immuno-enhancement and anticancer activities. They have some benefits not only in the clinical management of cancer but also of chronic infection. Also, it may be useful as an inducer of contrasuppressor T cells in immunocompromised individuals bearing suppressor T cells. In previous study, we evaluated heat production measured with a flow microcalorimeter in leukemic cell treated with Ge-132. Heat production from leukemic cell by germanium was increased dose dependent manner. In this study, we observed cellular change of shape and others in lukemic cells treated with germanium by electronic microscopy. Lukemic cells treated germanium showed significantly changes in ultrastructural aspects including various shape of nodule in cell surface, irregular surface of cellular membrane, smaller distribution of nuclear chromatin, and decreased surface of mitochondria. Correlations of ultrastructure and functional damage to mitochondria of L 1210 cells treated germanium were not clearly understood.

Source: Medicine and Biology. 1982, 104(5), 385~388.

3. 유기게르마늄을 투여한 쥐에서 분리한 혈청의 항암활성 (암과 화학요법)

Ability of sera from mice treated with Ge-132, an organogermanium compound, to inhibit experimental murine ascites tumors Fujio Suzuki
Dept. of Microbiology, Kumamoto University Medical School
 

Abstract

Serum specimens from mice treated orally with Ge-132 (100mg/kg) exhibited antitumor activity against Ehrlich (allogeneic) and RL ♂1 (syngeneic) ascites tumors in BALB/c mice. Sera obtained from mice 21 hours after Ge-132 administration displayed the highest antitumor effects and the antitumor activity was dode-dependent. Sera prepared from mice 12, 36, or 48 hours after Ge-132 treatment had no protective effect. Circulating interferon (IFN) was induced at 24 hours after administration. The antiviral activity of serum from Ge-132 treated mice was inactivated by treatment with trypsin, low pH, and anti-IFN- g antiserum. The inactivated preparation of serum IFN induced by Ge-132 did not show antitumor activity when administered to mice bearing Ehrlich ascites tumors. These results suggested that the antitumor activity in the sera of Ge-132 treated mice may have been expressed though IFN- g which was induced by Ge-132.

Source: Jpn. J. Cancer and Chemotherapy. 1985. 12(12), 2314~2321.

4. 유기게르마늄 화합물의 항종양효과 : 투여경로별 효과의 비교 (암과 화학요법)

Antitumor effect in mice of an organic germanium compound when different administration methods are used
Hisashi Aso, Emi Shibuya and Fujio Suzuki
Dept. of Microbiology, Kumamoto University Medical School
 

Abstract

The antitumor effects of an organic germanium compound, Ge-132, was examined in mice using two systems; one, the ascites form of Ehrlich carcimoma in DDI mice, and the other, the solid form form of Meth A fibrosarcoma in BALB/c mice. In the mice with Ehrlich ascites tumors, a remarkable prolongation in life span was observed after intraperitoneal (i.p.) or per oral (p.o.) administration of Ge-132 (300mg/kg), but not after intravenous (i.v.) injection of the compound. Followinf i.p. or p.o. administration, cytotoxic macrophages were induced in the peritoneal cavity after 18 hrs, although this was not the case after i.v. injection. When the in vivo effect of these in vitro active cytotoxic macrophage was examined after adoptive transfer to mice bearing Ehrlich ascites tumor cells, a significant antitumor effects was noted. In the mice bearing solid Meth A tumors, i.v. injection of Ge-132 (100mg/kg) were found to inhibit tumor growth remarkably, although i.p. and p.o. administration did not have the same results. This inhibitory effect of Ge-132 by i.v. administration was explained by the continued augmentation of NK activity in peripheral blood, which was followed by the induction of specific killer cells appearing in the spleen. When the mice which had recovered from Meth A tumor growth, following i.v. injection of Ge-132, were challenged with the same tumor on day 30, all mice were able to tolerate the challenge, but not a challenge of male RL1 tumor cells. These observation may indicate that the differing antitumor effects of Ge-132 produced when different administration methods are used can be explained by the variation in effector cells induced by such different administration routes.

Source: Jpn. J. Cancer and Chemotherapy. 1985. 12(12), 2345~2351.

5. 유기게르마늄을 투여한 쥐에서 분리한 마크로파지의 항종양활성 (암과 화학요법)

Suppression of tumor growth by peritoneal macrophages isolated from mice treated with carboxyethyl germanium sesquioxide
Fujio Suzuki
Dept of Microbiology, Kumamoto University Medical School

Abstract

In a murine model it has been shown that the antitumor activity of Ge-132 can be depleted by administration of macrophage blockers. In the present study, the role the macrophage plays in the antitumor activity of the compound was investigated. Oral administration of Ge-132 in mice was demonstrate to be effective in activating macrophage, and the cytotoxic activity of these macrophage appeared in the peritoneal cavity of mice 48 hours after oral administration of the compound. Co-cultivation of RL♂-1 leukemia or Ehrlich carcinoma cells with Ge-132 ?cytotoxic macrophage in vitro resulted in marked suppression of the growth of tumor cells. The transfer of peritoneal exudate cells (PEC), or purified macrophage fractions of PEC from Ge-132-treated mice to mice bearing Ehrlich or RL♂-1 ascites tumors resulted in significant protection. However, when the cytotoxic macrophages were depleted carbonyl-iron treatment in vitro, no antitumor effect was demonstrated in mice bearing Ehrlich or RL♂-1 ascites tumors. Macrophage fractions obtained from PEC of Ge-132-treated mice exhibited an inhibitory effect against certain tumors both in vivo and in vitro suggesting that the antitumor effect of Ge-132 observed in vivo resulted from the activation of macrophage.

 Source: Jpn. Cancer and Chemotherapy. 1985. 12(11), 2122~2128.

6. Sarcoma 180 유발 생쥐에 미치는 amygdaline과 carboxyethyl-germanium sesquioxide의  단독 및 병합 투여의영향      (서울 보건대 논문집)

Studies on the effects of Sarcoma 180 bearing mice after the treatment with Amygdaline and carboxyethyl germanium sesquioxide alone and in combination
Dong-Jin Rha
Dept of Medical Technology, Seoul Health Junior College.

Abstract

The Sarcoma 180 bearing mouse was experimentally induced and the chromosome variants and hematological findings were examined. Antitumor drug, that is, the span of life about the single or mutual combined of amygdaline and carboxyethy germanium sesquioxide, (GE-132) and change of each blood cell were examined.

The results obtained were as follows;

1. The number of the chromosome of the sarcoma 180 bearing mouse showed phenomenon of 41 - 68 hyperploid and the phenomenon of translocation and duplication among the chromosome showed clearly and double minute showed, too. The shape of the blood cell of the sarcoma 180 bearing mouse showed lots of heterochromatin and immature cell which had toxic granule and lymphocyte showed rieder cell.

2. Mean survival day of sarcoma 180 mouse found to be 21.22 days. On the other hand, the life span of antitumor drug, was extended the range from about 23 days (GE-132) to 25 days (Amygdaline), and the difference were recognized in each antitumor drugs. Life span of amygdaline and GE-132 in combined treatment was reflected to be extended more than that of GE-132 alone, but to be shortened than that of amygdaline alone.

3. The red blood cells of the sarcoma 180 bearing mouse were decreased on the l0th after tumor implantation. The white blood cells of sarcoma 180 bearing mouse were decreased on the 5th after tumor implantation. Each groups treated antitumor drug showed a tendency to decrease.

4. According to the comparative percentage of the leukocyte of the sarcoma 180 bearing mouse, neutrophil, eosinophil and monocyte were markedly increased, and conversely lymphocyte were markedly decreased.

Source: Annual Bulletin of Seoul health Junior college. 1986. 6,103-110

7. 암에 걸린 쥐에서 유기게르마늄의 항암효과 기전(carboxyethyl-germanium sesquioxide) (암과 화학요법)

Antitumor mechanisms of carboxyethyl germanium sesquioxide in mice bearing Ehrlich ascites tumors
Fujio Suzuki
Dept of Microbiology, Kumamoto University Medical School
 

Abstract

The administration of IFN containing sera (Ge-sera) obtained from Ge-132 treated mice (Ge-mice) or the passive transfer of macrophages (MØ) to mice bearing ascites tumors resulted in inhibition of tumor growth. The cooperative role of Ge-sera and Ge0-MØ in the display of Ge-132 anti tumor activity was studied. When mice were prepared with anti-mouse-IFNg antiserum, no IFN inducing or antitumor activities of the compound were detected. Cytotoxic activities were detected in peritoneal MØ of mice treated with Ge-sera, and passive transfer of these MØ to tumor bearing mice resulted in the inhibition of tumor growth. When tumor bearing mice were pretreated with substances toxic to MØ, no antitumor activity of Ge-sera was obtained. However, Ge-132 antitumor activity was observed in mice depleted of T cells, even though the antitumor effect of the compound itself were not demonstrable in T cell depleted mice. Therefore, a part of the antitumor activity of Ge-132 appears to be expressed as follow: (1) Ge-132 stimulates T cells to produce circulating lymphokine(s) which are inactivated by anti-IFNg treatment; (2) activated MØ are generated from resting MØ by these lymphokine(s); (3) the transplanted tumor are inhibited by these MØ.
 

Source: Jpn. Cancer and Chemotherapy. 1987. 14(1), 127~134.

혈 압 조 절

1. 쥐의 심혈관 기능과 박동에 있어서 유기게르마늄의 효과 (약리학)

Suppressive effect of organic germanium on Vaccinia virus infection
Iwao Umezawa and Kanki Komiyama.

The Kitasato Institute

Abstract

Ge-132 is one of potent biological response modifier (BRM) in human through activation of immunity. Induction of interferon and activation of NK cells and macrophages were achieved by administration of germanium. In this study, antiviral activity, one of another potent activities of organic germanium was investigated. The antiviral activity was measured by counting the plaque forming units (pfu) in each time. The pfu counting was minimal in the highest Ge-132 group at various treating times than control group when the DDY mice were infected with vaccina virus. It is clearly showed that Ge-132 can protect from vaccinia virus infection and propagation in mice. In other studies, induction of interferon and activation of NK cells and macrophages were achieved by administration of germanium. The propagation of virus was inhibited by germanium through activation of host’s immunity.

Source: Medicine and Biology. 1987. 114(6), 393~395.

 

 

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