REPRODUCTION STUDIES OF CARBOPLATIN(III) : Intravenous administration to rats during the perinatal and lactation periods
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With the widespread use of routine abdominal ultrasound examination during pregnancy, adnexal masses are observed with increasing frequency. Most patients are clinically asymptomatic at the time of presentation, and most of the adnexal masses detected during early pregnancy disappear during the first 16 weeks of pregnancy. Ovarian tumors are estimated to occur in about 1 in 1,000 pregnancies and of these 3% are malignant. Here we present an overview about frequency, diagnostic procedures and pathological characteristics of these ovarian tumors. Moreover, current modalities for treatment during pregnancy are summarized. Surgical treatment of the adnexal masses has to be performed with adequate staging and debulking equal to the treatment of non-pregnant women. However, whereas during organogenesis abortion has to be considered prior to chemotherapy, later in pregnancy surgical debulking as complete as possible, followed by taxol-platinum chemotherapy is indicated. If the fetus is not viable at the time of primary surgery, neoadjuvant chemotherapy and complementation of surgery after delivery of the baby should be performed. It should be stressed that chemotherapy for ovarian cancer applied during pregnancy appears to be safe. However, no studies have evaluated the long-term consequences for children exposed to intra-uterine chemotherapy. Aspiration of cysts should be avoided, as the correlation between the histological evaluation of an ovarian malignancy and the cytological evaluation of aspirates is poor. Moreover, spillage of malignant cysts is hazardous for the patient.
With the widespread use of routine abdominal ultrasound examination during pregnancy, adnexal masses are observed with increasing frequency. Most patients are clinically asymptomatic at the time of presentation, and most of the adnexal masses detected during early pregnancy disappear during the first 16 weeks of pregnancy. Ovarian tumors are estimated to occur in about 1 in 1,000 pregnancies and of these 3% are malignant. Here we present an overview about frequency, diagnostic procedures and pathological characteristics of these ovarian tumors. Moreover, current modalities for treatment during pregnancy are summarized. Surgical treatment of the adnexal masses has to be performed with adequate staging and debulking equal to the treatment of non-pregnant women. However, whereas during organogenesis abortion has to be considered prior to chemotherapy, later in pregnancy surgical debulking as complete as possible, followed by taxol-platinum chemotherapy is indicated. If the fetus is not viable at the time of primary surgery, neoadjuvant chemotherapy and complementation of surgery after delivery of the baby should be performed. It should be stressed that chemotherapy for ovarian cancer applied during pregnancy appears to be safe. However, no studies have evaluated the long-term consequences for children exposed to intra-uterine chemotherapy. Aspiration of cysts should be avoided, as the correlation between the histological evaluation of an ovarian malignancy and the cytological evaluation of aspirates is poor. Moreover, spillage of malignant cysts is hazardous for the patient.
Nickel (1–3) is a transition element in group VIII of the periodic system belonging with palladium and platinum to the 10 (nickel) triad. It is a silver‐white metal with characteristic gloss and is ductile and malleable. It occurs in two allotropic forms. The specific density of nickel is 8.90 g/cm 3 , melting point 1455°C, and boiling point 2730°C. Nickel is not soluble in water, but it does dissolve in dilute oxidizing acids. It is resistant to lyes. Nickel is obtained by processing sulfide and laterite ore concentrates using pyrometallurgic and hydrometallurgic processes. The resultant nickel matte obtained by roasting and smelting is subjected to further cleaning by electro‐, vapo‐, and hydrometallurgic refining methods. Some portion of the matte is roasted to obtain commercial nickel oxide agglomerate. Pure, 99.9% nickel can be obtained by electrolytic refining process. Nickel has been used predominantly as a component of alloys. Information on the acute and chronic poisonings by nickel metal in people is limited and, in the majority of cases, refers to effects of the combined exposure to dusts or fumes comprising mixtures of metallic nickel, and its oxides and salts. Contact hypersensitivity to nickel and its salts, however, is quite well documented. Ruthenium, a transition element, belongs to group VIII (iron) of the periodic classification and to the light platinum metals triad. It is a hard and brittle metal that resembles platinum. Ruthenium compounds are usually dark brown (ranging from yellow to black). Ruthenium forms alloys with platinum, palladium, cobalt, nickel, and tungsten. Elemental ruthenium occurs in native alloys of iridium and osmium (irridosmine, siskerite) and in sulfide and other ores (pentlandite, laurite, etc.) in very small quantities that are commercially recovered. Ruthenium is used in electronics and electrical engineering, and also in the chemical industry. Ruthenium metal is used as a catalyst in the oxidizing reactions and in the synthesis of long‐chain hydrocarbons. Because of its catalytic activity, it is also used in the catalytic converters for motor car engines. Ruthenium is used to increase the hardness of platinum alloys designed to make electric contacts, to make resistance wires, circuit breakers, and other components. It is also employed as a substitute for platinum in jewelry and to make the tips of fountain pen nibs. Certain derived ruthenium(III) complexes are used in cancer therapy to prevent metaplasia or to inhibit tumor cell growth. Ruthenium 106 is also used for that purpose. Ruthenium(III) complexes may be also applied to treat diseases resulting from exposure to nitric oxide. Ammoniated ruthenium oxychloride (Ruthenium Red) has been used as staining agent in microscopy. Rhodium is a transition element belonging to the cobalt group and to the light platinum triad at the same time. There is only one stable isotope: 103 Rh. Rhodium, in the elemental state, is a quite soft, forgeable, silver‐white metal. It occurs in nature extremely rarely (abundance: 1 × 10 −70 % by wt) in the form of alloys with other platinum metals ( e.g ., in crude platinum) or accompanies gold. Because it is a very precious and expensive metal, rhodium is resistant to the action of cold chlorine and fluorine and insoluble in acids and aqua regia. Pure rhodium is prepared by the reduction of its ammonium salt (dichloropentaaminorhodium). Rhodium is used for the manufacture of thermocouples (in the form of platinum–rhodium alloy: 10% Rh and 90% Pt), laboratory vessels (crucibles), catalysts (as an additive to Pt and Pd), spinnerets for synthetic and glass fibers, surgical tools (Ph, Pt, and Ir alloys), and electroplating. Besides, rhodium is used in jewelry, RhCl 3 is capable of controlling some viruses. Anticarcinogenic activity of some rhodium compounds has also been confirmed. No toxic rhodium and rhodium compounds levels have been determined either for blood or urine. As the exposure of animals to rhodium results in respiratory function disorders, it seems useful to monitor the pulmonary function in the case of rhodium poisoning. Considering that central nervous system disorders have been observed among animals exposed to rhodium, it seems advisable to monitor this system in the case of rhodium poisoning in humans. Palladium, a transition element belonging to Group III in the periodic table (nickel group) and light platinum metals, is a medium‐hard, moderately forgeable, ductile silver‐white metal. In its compounds, palladium usually assumes oxidation state +2 and +4, forming bivalent and tetravalent salts. A characteristic feature of palladium is its high hydrogen absorption, which allows for use its in the form of palladium sponge or palladium black as a catalyst in reduction processes. Contrary to other platinum metals, palladium is considerably less resistant to chemicals. At elevated temperatures palladium reacts with oxygen, fluorine, chlorine, sulfur, and selenium. Palladium dust may constitute fire and explosion hazards. Palladium compounds show different water solubility. Palladium metal is practically nontoxic. The acute effects of palladium compounds depend on the type, dose and administration of the compound. In general, the effects are stronger after IV or IP administration than orally. Water‐soluble palladium compounds, namely, those soluble in systemic fluids, show stronger toxic activity than do the insoluble ones. Osmium, a transition element belongs to the odd series 8 1 (iron) family, and at the same time to the heavy platinum metals. It has seven stable isotopes. Osmium is a very hard and brittle gray‐blue metal. It forms hexagonal crystals. No data have been found in the relevant literature concerning the toxic effects of osmium metal in experimental animals. However, it oxidizes at relatively low temperatures to the volatile osmium tetroxide, which shows strong irritating activity to eyes, respiratory tract and skin. Platinum, an intermediate element belonging to group VIII (nickel, palladium, platinum) of the periodic table and at the same time to the heavy platinum group, is a relatively soft, very malleable, ductile, silver‐white metal of very high melting point and high density. It occurs mainly in the form of stable isotopes: 190 Pt (0.01%), 192 Pt (0.08%), 194 Pt (32.9%), 195 Pt (33.8%), 196 Pt (25.2%), and 198 Pt (7.2%). It is rare in the earth crust (abundance 2 × 10 −6 % by weight). Nevertheless, platinum is the most abundant element of the heavy platinum group. Platinum is obtained mainly from copper and nickel ores, and platinum alloys and by recovery from the catalyst and other waste. The main stages of platinum production include extraction of the precious‐metal concentrate from the ore followed by separation through a complex refining process, during which the concentrate is dissolved in aqua regia, and the platinum is precipitated in the form of ammonium(IV) hexachloroplatinate. The precipitate is then calcinated at 600–700°C to give platinum sponge, which is then hardened by melting at high temperatures, such as in the electric arc. The resultant gray platinum sponge contains 99.95–99.9% pure metal. Platinum has been widely used in various industries, such as chemical, ceramic, electronic, automotive, petroleum. It is also used in medicine, dental surgery, and for jewelry manufacture. Pure platinum and its alloys are used to produce special‐purpose chemical apparatus, laboratory equipment (crucibles, evaporating dishes, platinum wire nets, electrodes), spinning dies for spinning chemical and glass fibers, and electric contacts. Platinum/iridium alloys are used to make length and weight standards. The industrial application of platinum is associated mainly with its catalytic activity. Platinum is used to make surgical instruments and implants. The industrial application of platinum is not limited to its pure metal or alloy forms; it is used also in the form of chemical compounds to electroplate metal surfaces.
Nickel is a transition element in group VIII of the periodic system belonging along with palladium and platinum to the 10 (nickel) triad. It is a silver‐white metal with characteristic gloss and is ductile and malleable. It occurs in two allotropic forms. The specific density of nickel is 8.90 g/cm 3 , melting point is 1455°C, and boiling point is 2730°C. Nickel is not soluble in water, but it does dissolve in dilute oxidizing acids. It is resistant to lyes. Nickel is obtained by processing sulfide and laterite ore concentrates using pyrometallurgic and hydrometallurgic processes. The resultant nickel matte obtained by roasting and smelting is subjected to further cleaning by electro‐, vapo‐, and hydrometallurgic refining methods. Some portion of the matte is roasted to obtain commercial nickel oxide agglomerate. Pure, 99.9% nickel can be obtained by electrolytic refining process. Nickel has been used predominantly as a component of alloys. Information on the acute and chronic poisonings by nickel metal in people is limited and in majority of cases refers to the effects of the combined exposure to dusts or fumes comprising mixtures of metallic nickel, and its oxides and salts. Contact hypersensitivity to nickel and its salts, however, is quite well documented. Ruthenium, a transition element, belongs to group VIII (iron) of the periodic classification and to the light platinum metals triad. It is a hard and brittle metal that resembles platinum. Ruthenium compounds are usually dark brown (ranging from yellow to black). Ruthenium forms alloys with platinum, palladium, cobalt, nickel, and tungsten. Elemental ruthenium occurs in native alloys of iridium and osmium (irridosmine, siskerite) and in sulfide and other ores (pentlandite, laurite, etc.) in very small quantities that are commercially recovered. Ruthenium is used in electronics, in electrical engineering, and in the chemical industry. Ruthenium metal is used as a catalyst in the oxidizing reactions and in the synthesis of long‐chain hydrocarbons. Because of its catalytic activity, it is also used in the catalytic converters for motor car engines. Ruthenium is used to increase the hardness of platinum alloys designed to make electric contacts and to make resistance wires, circuit breakers, and other components. It is also employed as a substitute for platinum in jewelry and to make the tips of fountain pen nibs. Certain derived ruthenium(III) complexes are used in cancer therapy to prevent metaplasia or to inhibit tumor cell growth. Ruthenium 106 is also used for that purpose. Ruthenium(III) complexes may also be applied to treat diseases resulting from exposure to nitric oxide. Ammoniated ruthenium oxychloride (Ruthenium Red) has been used as staining agent in microscopy. Rhodium is a transition element belonging both to the cobalt group and to the light platinum triad. There is only one stable isotope: . Rhodium, in the elemental state, is a quite soft, forgeable, silver‐white metal. It occurs in nature extremely rarely (abundance: 1 × 10 −70 % by wt) in the form of alloys with other platinum metals (e.g., in crude platinum) or accompanies gold. Because it is a very precious and expensive metal, rhodium is resistant to the action of cold chlorine and fluorine and insoluble in acids and aqua regia. Pure rhodium is prepared by the reduction of its ammonium salt (dichloropentaaminorhodium). Rhodium is used for the manufacture of thermocouples (in the form of platinum–rhodium alloy: 10% Rh and 90% Pt), laboratory vessels (crucibles), catalysts (as an additive to Pt and Pd), spinnerets for synthetic and glass fibers, surgical tools (Ph, Pt, and Ir alloys), and electroplating. Besides, rhodium is used in jewelry; RhCl 3 is capable of controlling some viruses. Anticarcinogenic activity of some rhodium compounds has also been confirmed. No toxic rhodium and rhodium compound levels have been determined either for blood or urine. As the exposure of animals to rhodium results in respiratory function disorders, it seems useful to monitor the pulmonary function in the case of rhodium poisoning. Considering that central nervous system disorders have been observed among animals exposed to rhodium, it seems advisable to monitor this system in the case of rhodium poisoning in humans. Palladium, a transition element belonging to group III in the periodic table (nickel group) and light platinum metals, is a medium‐hard, moderately forgeable, ductile silver‐white metal. In its compounds, palladium usually assumes oxidation state +2 and +4, forming bivalent and tetravalent salts. A characteristic feature of palladium is its high hydrogen absorption, which allows for its use in the form of palladium sponge or palladium black as a catalyst in reduction processes. Contrary to other platinum metals, palladium is considerably less resistant to chemicals. At elevated temperatures palladium reacts with oxygen, fluorine, chlorine, sulfur, and selenium. Palladium dust may constitute fire and explosion hazards. Palladium compounds show different water solubility. Palladium metal is practically nontoxic. The acute effects of palladium compounds depend on the type, dose, and administration of the compound. In general, the effects are stronger after IV or IP administration than oral administration. Water‐soluble palladium compounds, namely, those soluble in systemic fluids, show stronger toxic activity than do the insoluble ones. Osmium, a transition element belongs to the odd series 8 1 (iron) family and at the same time to the heavy platinum metals. It has seven stable isotopes. Osmium is a very hard and brittle gray‐blue metal. It forms hexagonal crystals. No data have been found in the relevant literature concerning the toxic effects of osmium metal in experimental animals. However, it oxidizes at relatively low temperatures to the volatile osmium tetroxide, which shows strong irritating effect on eyes, respiratory tract, and skin. Platinum, an intermediate element belonging to group VIII (nickel, palladium, and platinum) of the periodic table and at the same time to the heavy platinum group, is a relatively soft, very malleable, ductile, silver‐white metal of very high melting point and high density. It occurs mainly in the form of stable isotopes: (0.01%), (0.08%), (32.9%), (33.8%), (25.2%), and (7.2%). It is rare in the earth crust (abundance 2 × 10 −6 % by weight). Nevertheless, platinum is the most abundant element of the heavy platinum group. Platinum is obtained mainly from copper and nickel ores and platinum alloys, and by recovery from the catalyst and other waste. The main stages of platinum production include extraction of the precious metal concentrate from the ore followed by separation through a complex refining process, during which the concentrate is dissolved in aqua regia and platinum is precipitated in the form of ammonium(IV) hexachloroplatinate. The precipitate is then calcinated at 600–700°C to give platinum sponge, which is then hardened by melting at high temperatures, such as in the electric arc. The resultant gray platinum sponge contains 99.95–99.9% pure metal. Platinum has been widely used in various industries, such as chemical, ceramic, electronic, automotive, and petroleum. It is also used in medicine, in dental surgery, and in jewelry manufacture. Pure platinum and its alloys are used to produce special‐purpose chemical apparatus, laboratory equipment (crucibles, evaporating dishes, platinum wire nets, and electrodes), spinning dies for spinning chemical and glass fibers, and electric contacts. Platinum/iridium alloys are used to make length and weight standards. The industrial application of platinum is associated mainly with its catalytic activity. Platinum is used to make surgical instruments and implants. The industrial application of platinum is not limited to its pure metal or alloy forms; it is also used in the form of chemical compounds to electroplate metal surfaces.
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