• Title/Summary/Keyword: Al toxicity

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Comparison of Liver, Kidney, Bone Metal Concentration in OhJeokSan-Treated Rats (오적산(五積散)을 투여한 흰쥐의 간장, 신장, 골중 금속농도 비교에 관한 연구)

  • Park Chul-Soo;Lee Sun-Dong;Park Hae-Mo;Park Yeong-Chul
    • Journal of Society of Preventive Korean Medicine
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    • v.6 no.2
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    • pp.66-85
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    • 2002
  • Traditional herbal medicine is used extensively among the Korean populations, and other Asian countries employ similar therapies as well In recent years, extensive focus was laid on adulteration of the herbal medicine with heavy metals. This may be mainly due to a soil contamination by an environmental pollution. The objective of this study is to identify the contents of various heavy metals in the blood from OhJeokSan-Decoction (OD) treated-rats. For this study, 13 kinds of metals including essential and heavy metals, i.e. Al, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se and Zn were analyzed by a slight modification of EPA methods and the following results are obtained. ; 1. There is no significant difference between the OD-treated groups and control group in liver, kidney, bone, brain, weight, food intake. 2. The amount of each metal analyzed in the liver are as follows; Al ; $0.235{\sim}4.215mg/kg$, As ; $0.103{\sim}0.461mg/kg$, Cd ; $0.005{\sim}0.010mg/kg$, Co ; $0.017{\sim}0.046mg/kg$, Cr ; $0.137{\sim}0.403mg/kg$, Cu ; $1.736{\sim}4.827mg/kg$, Fe ; $54.472{\sim}381.447mg/kg$, Hg ; not detected, Mn ; $1.159{\sim}2.803mg/kg$, Ni ; $0.007{\sim}0.095mg/kg$, Pb ; not detected, Se ; $0.682{\sim}1.887mg/kg$, Zn ; $10.213{\sim}26.119mg/kg$, by groups, respectively. In control and other experimental group, several metal (Co, Cu, Mn, Zn, As, Cr) has a significant difference, but in experimental I and other experimental II, III, IV, V groups, there are no significant difference. 3. The amount of each metal analyzed in the kidney are as follows; Al ; $1.712{\sim}31.230mg/kg$, As ; $0.062{\sim}0.439mg/kg$, Cd ; $0.010{\sim}0.062mg/kg$, Co ; $0.000{\sim}0.101mg/kg$, Cr ; $0.125{\sim}0.636mg/kg$, Cu ; $3.385{\sim}12.502mg/kg$, Fe ; $41.148{\sim}99.709mg/kg$, Hg ; $0.000{\sim}0.270mg/kg$, Mn ; $0.433{\sim}2.301mg/kg$, Ni ; $0.000{\sim}0.221mg/kg$, Pb ; $0.000{\sim}0.584mg/kg$, Se ; $0.540{\sim}1.600mg/kg$, Zn ; $8.775{\sim}17.060mg/kg$, by groups, respectively. The concentration of Cu, Se, Cr, and Hg are variated significantly in control and other experimental group, and Cu, Se, Cd, Cr are variated significantly in experimental I and other experimental II, III, IV, V groups. 4. The amount of each metal analyzed in the bone(tibia and fibula) are as follows; Al ; $9.557{\sim}119.464mg/kg$, As ; $0.139{\sim}12.250mg/kg$, Cd ; $0.000{\sim}0.295mg/kg$, Co ; $0.022{\sim}0.243mg/kg$, Cr ; $0.239{\sim}1.999mg/kg$, Cu ; $0.000{\sim}2.291mg/kg$, Fe ; $240.249{\sim}841.956mg/kg$, Hg ; $0.000{\sim}0.983mg/kg$, Mn ; $0.214{\sim}7.353mg/kg$, Ni ; $5.473{\sim}11.453mg/kg$, Pb ; $0.000{\sim}8.502mg/kg$, Se ; $0.000{\sim}3.005mg/kg$, Zn ; $61.158{\sim}195.038mg/kg$, by groups, respectively. The concentration of Se, Cd are variated significantly in control and other experimental groups, and Se is variated significantly in experimental I and other experimental II, III, IV, V groups. 5. Exceptionally several metal concentration is increased or decreased. but there is no significant harmful difference of metal concentration in the liver, kidney and bone, from the OD-treated-rats compared to those of the control group even if higher dosage($1{\sim}8$ times dosage of person) of OD was administered. Thus, it is expected that the herbal decoction in the traditional herbal medicine would not lay any burden on the body and the heavy metal toxins would not affect our physiological system. However, other kinds of herbal treatment, such as i.v. and i.p. should be considered in terms of metal toxicity in the body since the level of certain metal.

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Studies of Liming Effect on the Improvement of an Acid Sulphate Paddy Soil (특이산성답(特異酸性畓) 토양(土壤)의 개량(改良)을 위(爲)한 석회시용(石灰施用) 효과(?果)에 관(關)한 연구(硏究))

  • Park, Young-Sun
    • Applied Biological Chemistry
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    • v.17 no.3
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    • pp.193-218
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    • 1974
  • These studies were carried out for the elucidation of liming effect on the growth of rice seedlings and the chemical characteristics of an acid sulphate paddy that shows not only extremely high acidity of soil but also poor growth of rice plants, consequently low yield. Thus the liming effect on the changes of acidity, oxidation-reduction potential, and the contents of iron, aluminium, sulphate, and phosphorus fractions in the soil was investigated under the waterlogging and drying condition. The reclaimable or inhibitory effect of phosphorus, iron and aluminium on the growth of rice seedlings was also investigated under liming. The results are summarized as follows: 1. After liming, the pH of the acid sulphate subsoil decreased again on drying. 2. The oxidation-reduction potential reached a minimum after 5 days of flooding and greatly decreased on liming but increased after drying. 3. The contents of ferrous iron soluble in water-and Morgan's solution reached a maximum after 15 days of flooding and only the content of water soluble ferrous iron was greatly decreased. 4. The content of aluminium soluble in water-and Morgan's solution decreased by flooding and liming, and showed a tendency to increase on drying. 5. In the limed acid sulphate soil, the content of water soluble calcium showed a highly significant negative correlation with the content of sulphate and liming decreased sulphate content in the soil. 6. The contents of total phosphorus was 496.3 ppm in the acid sulphate topsoil and 387.5 ppm in the subsoil. The content of each phosphorus fraction was in the order of Fe-P>Occ. Fe-P>Ca-P>Occ. Al-P>Al-P and Fe-P content in the soil was the highest fraction among them. 7. Lime application increased greatly Ca-P and Al-P, and Occ. Fe-P and Occ. Al-P only slightly, but decreased Fe-P differently in each soil. 8. Effect of phosphorus on the dry matter yield of rice seedlings was great. The optimum amount of phosphorus to produce maximum dry matter yield of rice seedlings appeared to be 6.8% of maximum absorption (absorption coefficient) without liming and 10.0% with liming. 9. In rice seedlings liming increased the content and uptake of calcium and silica but decreased those of iron and aluminium. Phosphorus application increased the content and uptake of phosphorus and decreased iron while the application of iron and aluminium increased their contents and uptake but decreased those of phosphorus. 10. Liming greatly alleviated such toxicity of iron and aluminium. 11. When phosphorus was applied, the dry matter yield of rice seedlings showed highly significant positive correlations with uptake of phosphorus, calcium and silica each. When iron and aluminium were applied, dry matter yields indicated significant positive correlations with the contents or uptake of calcium and silica each, but significant negative correlations with the content or uptake of iron and aluminium. 12. Under the application of phosphorus and lime, dry matter yields showed significant positive correlations with pH and Morgan's extractable calcium each of the soil samples after harvest. Under the application of lime, iron and aluminium, dry matter yields showed significant positive correlations with pH, calcium and silica each, but negative correlations with iron and aluminium contents each of the soil samples after harvest.

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Monitoring of Seasonal Water Quality Variations and Environmental Contamination in the Sambo Mine Creek, Korea (삼보광산 하류 수계의 계절별 수질변화와 오염도 평가)

  • Jung, Goo-Bok;Lee, Jong-Sik;Kim, Won-Il;Ryu, Jong-Su;Yun, Sun-Gang
    • Korean Journal of Environmental Agriculture
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    • v.27 no.4
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    • pp.328-336
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    • 2008
  • Metal mining district drainage is a well recognized source of environmental contamination. Oxidation of metal sulfides produces acidic and metal-rich waters that contaminate local surface water and ground water in mines, mine dumps, and tailing impoundments. This monitoring study was carried out to investigate the stream water quality and pollution as affected by the Sambo mine drainage in relation to the relative distance from the mine. It obvious that pH values of the mine drainage ranged from 5.8 to 6.9, while the average concentrations of the dissolved chemical constituents for EC, $SO_4^{2-}$, $K^+$, $Ca^{2+}$, and $Mg^{2+}$ were $1.77\;dS\;m^{-1}$, 929, 14.6, 263.3, and 46.9 mg/L in mine drainage discharged from the main waste rock dumps (WRD), respectively. Furthermore, EC values and sulfate concentrations exceeded the critical toxicity levels in agricultural water for rice plant ($1.0\;dS\;m^{-1}$ for EC and 54.0 mg/L for $SO_4^{2-}$). Also, the average of dissolved cadmium concentrations ($0.016{\sim}0.021\;mg/L$) was higher than water quality standard (0.01 mg/L) for agricultural water in Korea, in addition to Zn, Fe and Mn were higher than trace metals maximum concentrations which recommended by FAO for irrigation water. The results indicate that mine drainage discharged from the Sambo mine affected stream water at least to distance of 1 km downstream of the mine water discharge point. EC values, $SO_4^{2-}$ and $Ca^{2+}$ concentrations in discharged water positively correlated with dissolved Cd, Zn, Al and Mn concentrations, while the pH values negatively correlated. In addition, EC values, $SO_4^{2-}$ and $Ca^{2+}$ concentrations were negatively correlated with pH values.

Decomposition of Eco-friendly Liquid Propellants over Ruthenium/Al2O3/metal foam Catalysts (Ru/Al2O3/메탈폼 촉매를 이용한 친환경 액체추진제 분해)

  • Yoo, Dalsan;Jeon, Jong-Ki
    • Clean Technology
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    • v.25 no.3
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    • pp.256-262
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    • 2019
  • Hydroxylammonium nitrate (HAN)-based liquid propellants are attracting attention as environmentally friendly propellants because they are not carcinogens and the combustion gases have little toxicity. The catalyst used to decompose the HAN-based liquid propellant in a thruster must have both low temperature activity and high heat resistance. The objective of this study is to prepare an Ru/alumina/metal foam catalyst by supporting alumina slurry on the surface of NiCrAl metal foam using a washing coating method and then to support a ruthenium precursor thereon. The decomposition activity of a HAN aqueous solution of the Ru/alumina/metal foam catalyst was evaluated. The effect of the number of repetitive coatings of alumina slurry on the physical properties of the alumina/metal foam was analyzed. As the number of alumina wash coatings increased, mesopores with a diameter of about 7 nm were well-developed, thereby increasing the surface area and pore volume. It was optimal to repeat the wash coating alumina on the metal foam 12 times to maximize the surface area and pore volume of the alumina/metal foam. Mesopores were also well developed on the surface of the Ru/alumina/metal foam catalyst. It was found that the metal form itself without the active metal and alumina can promote the decomposition reaction of the HAN aqueous solution. In the case of the Ru/alumina/metal foam-550 catalyst, the decomposition onset temperature was significantly lowered compared with that of the thermal decomposition reaction, and ${\Delta}P$ could be greatly increased in the decomposition of the HAN aqueous solution. However, when the catalyst was calcined at $1,200^{\circ}C$, the catalytic activity was lowered inevitably because the surface area and pore volume of the catalyst were drastically reduced and Ru was sintered. Further research is needed to improve the heat resistance of Ru/alumina/metal foam catalysts.

Manganese and Iron Interaction: a Mechanism of Manganese-Induced Parkinsonism

  • Zheng, Wei
    • Proceedings of the Korea Environmental Mutagen Society Conference
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    • 2003.10a
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    • pp.34-63
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    • 2003
  • Occupational and environmental exposure to manganese continue to represent a realistic public health problem in both developed and developing countries. Increased utility of MMT as a replacement for lead in gasoline creates a new source of environmental exposure to manganese. It is, therefore, imperative that further attention be directed at molecular neurotoxicology of manganese. A Need for a more complete understanding of manganese functions both in health and disease, and for a better defined role of manganese in iron metabolism is well substantiated. The in-depth studies in this area should provide novel information on the potential public health risk associated with manganese exposure. It will also explore novel mechanism(s) of manganese-induced neurotoxicity from the angle of Mn-Fe interaction at both systemic and cellular levels. More importantly, the result of these studies will offer clues to the etiology of IPD and its associated abnormal iron and energy metabolism. To achieve these goals, however, a number of outstanding questions remain to be resolved. First, one must understand what species of manganese in the biological matrices plays critical role in the induction of neurotoxicity, Mn(II) or Mn(III)? In our own studies with aconitase, Cpx-I, and Cpx-II, manganese was added to the buffers as the divalent salt, i.e., $MnCl_2$. While it is quite reasonable to suggest that the effect on aconitase and/or Cpx-I activites was associated with the divalent species of manganese, the experimental design does not preclude the possibility that a manganese species of higher oxidation state, such as Mn(III), is required for the induction of these effects. The ionic radius of Mn(III) is 65 ppm, which is similar to the ionic size to Fe(III) (65 ppm at the high spin state) in aconitase (Nieboer and Fletcher, 1996; Sneed et al., 1953). Thus it is plausible that the higher oxidation state of manganese optimally fits into the geometric space of aconitase, serving as the active species in this enzymatic reaction. In the current literature, most of the studies on manganese toxicity have used Mn(II) as $MnCl_2$ rather than Mn(III). The obvious advantage of Mn(II) is its good water solubility, which allows effortless preparation in either in vivo or in vitro investigation, whereas almost all of the Mn(III) salt products on the comparison between two valent manganese species nearly infeasible. Thus a more intimate collaboration with physiochemists to develop a better way to study Mn(III) species in biological matrices is pressingly needed. Second, In spite of the special affinity of manganese for mitochondria and its similar chemical properties to iron, there is a sound reason to postulate that manganese may act as an iron surrogate in certain iron-requiring enzymes. It is, therefore, imperative to design the physiochemical studies to determine whether manganese can indeed exchange with iron in proteins, and to understand how manganese interacts with tertiary structure of proteins. The studies on binding properties (such as affinity constant, dissociation parameter, etc.) of manganese and iron to key enzymes associated with iron and energy regulation would add additional information to our knowledge of Mn-Fe neurotoxicity. Third, manganese exposure, either in vivo or in vitro, promotes cellular overload of iron. It is still unclear, however, how exactly manganese interacts with cellular iron regulatory processes and what is the mechanism underlying this cellular iron overload. As discussed above, the binding of IRP-I to TfR mRNA leads to the expression of TfR, thereby increasing cellular iron uptake. The sequence encoding TfR mRNA, in particular IRE fragments, has been well-documented in literature. It is therefore possible to use molecular technique to elaborate whether manganese cytotoxicity influences the mRNA expression of iron regulatory proteins and how manganese exposure alters the binding activity of IPRs to TfR mRNA. Finally, the current manganese investigation has largely focused on the issues ranging from disposition/toxicity study to the characterization of clinical symptoms. Much less has been done regarding the risk assessment of environmenta/occupational exposure. One of the unsolved, pressing puzzles is the lack of reliable biomarker(s) for manganese-induced neurologic lesions in long-term, low-level exposure situation. Lack of such a diagnostic means renders it impossible to assess the human health risk and long-term social impact associated with potentially elevated manganese in environment. The biochemical interaction between manganese and iron, particularly the ensuing subtle changes of certain relevant proteins, provides the opportunity to identify and develop such a specific biomarker for manganese-induced neuronal damage. By learning the molecular mechanism of cytotoxicity, one will be able to find a better way for prediction and treatment of manganese-initiated neurodegenerative diseases.

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Cumulative Risk Assessment of Organophosphorus Pesticides in the Diet (식품을 통한 유기인계농약류의 동시노출위해성평가)

  • 이효민;한지연;윤은경;김효미;황인균;최동미;이강봉;원경풍;송인상
    • Journal of Food Hygiene and Safety
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    • v.16 no.1
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    • pp.21-26
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    • 2001
  • Risk assessment traditionally are conducted on individual chemicals; however, humans are exposed to multiple chemicals in daily life. The organophosphorus (OP) pesticides are considered in a single risk assessment because they act by a common mechanism of toxicity, and there is likely to be expose to multiple OP pesticides simultaneously or sequentially. The OP pesticides act by inhibiting the enzyme acetylcholinesterasc (AChE) and have available extensive database. AChE is widely distributed throughout the body, most importantly in the nervous system. Inhibition of AChE results in accumulation of acetylcholine in the nervous system that results in clinical signs of cholinergic toxicity, including increased salivation and lacrimation, nausea and vomiting, muscle fasciculation, lethargy and fatigue, among others. To conduct an exposure assessment for pesticides in the diet, we need to know the food consumption patterns of the populations, and the pesticide residue levels in the foods that are consumed. This study was conducted to identify cumulative dietary risk due to multiple OP pesticides that can be exposed through various foods. Total 22 food samples including cereals, vegetables and fruits were collected randomly two times from food markets in several sites (4 cities). The subjected foods were selected by regarding of highly consumed foods to general Korean people. The 12 OP pesticides including Acephate, Azinphos-methyl, Chlorpyrifos, and Diazinon were monitored. For the exposure assessment, general adult group of 60 kg body weight was regarded as target population and food consumption data suggested by Lee et al. (2000) were used as consumed value of individual food. Analyses of samples for OP pesticides have been carried out according to the multiclass multiresidue analysis method and acephate and methamidophos analysis method of Korea Food Code. In general the levels of OP pesticides found in the food samples were very low or not detected.

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A Case of Interstitial Pneumonitis developed by Interferon-${\alpha}$ Treatment for Chronic Hepatitis C (만성 C형 간염 환자에서 Interferon-${\alpha}$를 투여중 발생한 간질성 폐렴 1예)

  • Yoon, Jong Goo;Ahn, Joong Hyun;Ko, Seung Hyeon;Lee, Hyun Seoung;Kwon, Soon Seog;Kim, Young Kyoon;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.4
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    • pp.637-644
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    • 1996
  • Interstitial pneumonitis associated with interferon alpha therapy for chronic hepatitis C was first describe6 in 1994 by Kazoo et al In Japan. The mechanism of interstitial pneumonitis developed by interferon alpha was still unknown but immunologic, allergic of direct lung toxicity were suggested. We experienced a case of interstitial pneumonitis developed during interferon alpha therapy for chronic hepatitis C in a 52-year-old male patient. He was treated with 6 million units of interferon alpha intramuscularly 3 times per week for 4 weeks and noted progressive dyspnea and cough. These symptoms were subsided after 6 weeks' discontinuation of interferon alpha therapy. And so, he was retreated with 3 million units of interferon alpha 3 times per week for 8 weeks and felt dyspnea again. He was admitted to our hospital for further evaluation of progressive dyspnea. Arterial blood gas(ABG) values were $PaO_2$ 90.7 mmHg and $PaCO_2$ 31.9 mmHg, and antinuclear antibody(ANA) was negative. A chest X-ray film revealed diffuse reticulo-nodular shadows in bilateral lung fields, suggesting a diagnosis of interstitial pneumonitis. A marked increase in lymphocyte count and suppressor T cell were observed in bronchoalveolar lavage(BAL) fluid. Lymphocyte stimulation test with interferon alpha was positive. Interstitial pneumonitis was confirmed by transbronchial lung biopsy. After discontinuation of interferon alpha, we gave oral steroid in the condition that clinical symptoms were being improved gradually.

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Effect of Carbamazepine on the Ouabain-Induced Arrhythmia in Rabbits (가토의 Quabain-Induced Arrhythmia에 미치는 Carbamzepine의 효과)

  • Kim, Eui-Hong;Ha, Jeoung-Hee;Lee, Kwang-Youn;Kim, Won-Joon
    • Journal of Yeungnam Medical Science
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    • v.3 no.1
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    • pp.279-285
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    • 1986
  • Carbamazepine is a derivative of iminostilbene with carbamyl group and related chemically to the tricyclic antidepressants. Carbamazepine has been introduced for treatment of trigeminal neuralgia. Recently it is used as an antiepileptic agent such as diphenylhydantoin. Antiepileptic drugs are known to affect experimentally induced cardiac arrhythmia and are now widely used clinically for treatment of ventricular tachyarrhythmias, particularly those produced by digitalis intoxication. Steiner et al.(1970) reported that carbamazepine was found to be very effective in converting ventricular tachycardia due to digitalis toxicity to normal sinus rhythm. Clinically bradycardia, complete heart block, ventricular standstill and Adams-stokes attack were reported in the course of carbamazepine treatment. The purpose of this study was to investigate the effects of carbamazepine on the ouabain-induced arrhythmia in vivo. The rabbits of either sex, weighing from 1.6 to 3.2kg were anesthesized by urethane. After the trachea was cannulated, the rabbits were ventilated with room air using a respirator. Drugs were given into polyethylene cannula in the femoral vein. Blood pressure were recorded by physiograph via pressure tranducer connected with the cannula in the femoral artery. EKG were recorded by Physiograph via electrode implanted in both fore leg and left hind leg. The results are summarized as follows; 1. Arrhythmia was induced by continuous infusion of ouabain.($64{\pm}8.8{\mu}g/kg$) 2. Single administration of ouabain($64{\mu}g/kg$) induced arrhythmia which was persisted for 7-8 min. 3. Ouabain induced arrhythmia was restored to normal sinus rhythm by administration of carbamazepine.(The more dosage, the less frequent and the longer duration) 4. Severe bradycardia, A-V block, atrial fibrillation were seen on the EKG after injection of carbamazepine alone. By the above results, it may be concluded that carbamazepine inhibits the ouabain-induced arrhythmia by dose-dependent.

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Establishment of the Korean Tolerable Daily Intake of Bisphenol A Based on Risk Assessments by an Expert Committee

  • Choi, Chan-Woong;Jeong, Ji-Yoon;Hwang, Myung-Sil;Jung, Ki-Kyung;Lee, Kwang-Ho;Lee, Hyo-Min
    • Toxicological Research
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    • v.26 no.4
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    • pp.285-291
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    • 2010
  • Recently, reproductive and neurobehavioral effects of bisphenol A (BPA) have been documented, and thus a review was requested for BPA management direction by the government. Therefore, this study was performed to establish a Korean tolerable daily intake (TDI) for BPA. An expert committee, consisting of specialists in fields such as toxicology, medicine, pharmacology, and statistics, was asked to evaluate BPA health based guidance values (HbGVs). Although many toxicological studies were reviewed to select a point of departure (POD) for TDI, rat and mouse reproductive studies by Tyl et al. (2002, 2006), which were performed according to GLP standards and OECD guidelines, were selected. This POD was the lowest value determined from the most sensitive toxicological test. The POD, a NOAEL of 5 mg/kg bw/day, was selected based on its systemic toxicity as critical effects. An uncertainty factor of 100 including interspecies and intraspecies differences was applied to calculate the TDI. According to the evaluation results, a TDI of BPA for Korean was suggested at 0.05 mg/kg bw/day. In addition, the BPA exposure level based on food consumption by the Korean population was estimated as 1.509 ${\mu}g/kg$ bw/day, and the HI was evaluated at 0.03 when the TDI of 0.05 mg/kg bw/day was applied. This HI value of 0.03 indicated that hazardous effects would not be expected from BPA oral exposures. Although highly uncertain, further studies on low dose neurobehavioral effects of BPA should be performed. In addition, it is recommended that the 'as low as reasonably achievable' (ALARA) principle be applied for BPA exposure from food packaging materials in newborn infants and children.

Aromatase Inhibition and Capecitabine Combination as 1st or 2nd Line Treatment for Metastatic Breast Cancer - a Retrospective Analysis

  • Shankar, Abhishek;Roy, Shubham;Rath, Goura Kishor;Julka, Pramod Kumar;Kamal, Vineet Kumar;Malik, Abhidha;Patil, Jaineet;Jeyaraj, Pamela Alice;Mahajan, Manmohan K
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6359-6364
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    • 2015
  • Background: Preclinical studies have shown that the combination of an aromatase inhibitor (AI) and capecitabine in estrogen receptor (ER)- positive cell lines enhance antitumor efficacy. This retrospective analysis of a group of patients with metastatic breast cancer (MBC) evaluated the efficacy and safety of combined AI with capecitabine. Materials and Methods: Patients with hormone receptor-positive metastatic breast cancer treated between 1st January 2005 and 31st December 2010 with a combination of capecitabine and AI were evaluated and outcomes were compared with those of women treated with capecitabine in conventional dose or AI as a monotherapy. Results: Of 72 patients evaluated, 31 received the combination treatment, 22 AI and 19 capecitabine. The combination was used in 20 patients as first-line and 11 as second-line treatment. Mean age was 46.2 years with a range of 28-72 years. At the time of progression, 97% had a performance status of <2 and 55% had visceral disease. No significant difference was observed between the three groups according to clinical and pathological features. Mean follow up was 38 months with a range of 16-66 months. The median PFS of first-line treatment was significantly better for the combination (PFS 21 months vs 8.0 months for capecitabine and 15.0 months for AI). For second-line treatment, the PFS was longer in the combination compared with capecitabine and Al groups (18 months vs. 5.0 months vs. 11.0 months, respectively). Median 2 year and 5 year survival did not show any significant differences among combination and monotherapy groups. The most common adverse events for the combination group were grade 1 and 2 hand-for syndrome (69%), grade 1 fatigue (64%) and grade 1 diarrhoea (29%). Three grade 3 hand-foot syndrome events were reported. Conclusions: Combination treatment with capecitabine and AI used as a first line or second line treatment was safe with much lowered toxicity. Prospective randomized clinical trials should evaluate the use of combination therapy in advanced breast cancer to confirm these findings.