ABSTRACT
Abstract The bats usually inhabit shelters with favorable conditions for fungal proliferation, including pathogenic and opportunistic species. The fungal diversity present on bats is little known and the studies are scarce in Brazil, which only a work has been performed in Cerrado and Pantanal biomes. Therefore, the objective of this study was evaluating the occurrence of filamentous fungi on the rostral region of Molossus molossus in an Atlantic Forest remnant of Brazil. The bats were captured with mist nets installed outside a shelter located in the municipality of Treviso, (28°29'23"S and 49°31'23"W), south region of state Santa Catarina. With a swab sterile moistened in saline solution, samples from the rostral region were obtained from all captured M. molossus individuals. The samples were taken to the laboratory for analysis and isolation in different culture media, followed of identification of fungal through the microculture technique. In total, 15 individuals were captured, which five fungal genus and 19 taxa were identified. Among the taxa registered, Aspergillioides sp.2, (47%), Penicillium sp.1 (33%), Chrysonilia sp. (33%), Cladosporium sp. (27%) were classified as little constant. In terms of abundance, Penicillium sp.1 (34%), Aspergillioides sp.2 (21%) and Aspergillus sp.2 (11%) were the most abundant in the samples. The results showed the occurrence of high diversity fungal in the rostral region of M. molossus in the Atlantic Forest, which is higher than observed in others Brazilian biomes. Some fungal genera found may harbor pathogenic and opportunistic species that need to be identified for preventing potential disease well as for bat conservation projects.
Resumo Os morcegos comumente abrigam-se em locais com condições favoráveis para proliferação fúngica, incluindo espécies patogênicas e oportunistas. A diversidade fúngica presente nos morcegos é pouco conhecida e os estudos são escassos no Brasil, no qual apenas um trabalho tem sido realizado nos biomas do Cerrado e Pantanal. Portanto, o objetivo deste estudo foi avaliar a ocorrência de fungos filamentosos na região rostral de Molossus molossus em um remanescente da Mata Atlântica no sul do Brasil. Os morcegos foram capturados com redes-de-neblina instaladas na saída de um abrigo localizado no município de Treviso (28°29'23"S e 49°31'23"W), região sul do estado de Santa Catarina. Com um swab esterilizado e umedecido em solução salina, amostras da região rostral foram obtidas de todos os indivíduos de M. molossus capturados. As amostras foram levadas ao laboratório para análise e isolamento em diferentes meios de cultura, seguido de identificação taxonômica fúngica pela técnica de microcultivo. No total, 15 indivíduos foram capturados, nos quais 5 gêneros fúngicos e 19 taxa foram identificados. Dentre os taxa registrados foram classificados como pouco constante Aspergillioides sp.2, (47%), Penicillium sp.1 (33%), Chrysonilia sp. (33%), Cladosporium sp. (27%). Em termos de abundância, Penicillium sp.1 (34%), Aspergillioides sp.2 (21%) e Aspergillus sp.2 (11%) foram os mais abundantes nas amostras. Os resultados mostraram ocorrência de elevada riqueza de fungos na região rostral de M. molossus na Mata Atlântica, riqueza essa que é superior àquela observada para outros biomas brasileiros. Alguns gêneros fúngicos encontrados podem abrigar espécies patogênicas e oportunistas que precisam ser identificadas tanto para prevenir potenciais doenças, assim como, para os projetos de conservação dos morcegos.
Subject(s)
Humans , Animals , Chiroptera , Aspergillus , Brazil , Forests , EcosystemABSTRACT
The bats usually inhabit shelters with favorable conditions for fungal proliferation, including pathogenic and opportunistic species. The fungal diversity present on bats is little known and the studies are scarce in Brazil, which only a work has been performed in Cerrado and Pantanal biomes. Therefore, the objective of this study was evaluating the occurrence of filamentous fungi on the rostral region of Molossus molossus in an Atlantic Forest remnant of Brazil. The bats were captured with mist nets installed outside a shelter located in the municipality of Treviso, (28°29'23"S and 49°31'23"W), south region of state Santa Catarina. With a swab sterile moistened in saline solution, samples from the rostral region were obtained from all captured M. molossus individuals. The samples were taken to the laboratory for analysis and isolation in different culture media, followed of identification of fungal through the microculture technique. In total, 15 individuals were captured, which five fungal genus and 19 taxa were identified. Among the taxa registered, Aspergillioides sp.2, (47%), Penicillium sp.1 (33%), Chrysonilia sp. (33%), Cladosporium sp. (27%) were classified as little constant. In terms of abundance, Penicillium sp.1 (34%), Aspergillioides sp.2 (21%) and Aspergillus sp.2 (11%) were the most abundant in the samples. The results showed the occurrence of high diversity fungal in the rostral region of M. molossus in the Atlantic Forest, which is higher than observed in others Brazilian biomes. Some fungal genera found may harbor pathogenic and opportunistic species that need to be identified for preventing potential disease well as for bat conservation projects.
Subject(s)
Chiroptera , Animals , Aspergillus , Brazil , Ecosystem , Forests , HumansABSTRACT
Barley (Hordeum vulgare L.) is an important cereal crop for food and represents one of the main ingredients in beer production. Considering the importance of barley and its derived products, the knowledge about the mycotoxin contamination in the barley production is essential in order to assess its safety. In this study, the levels of deoxynivalenol (DON) and zearalenone (ZEN) in brewing barley were determined using a LC-MS/MS method. A survey was conducted in 2015 to estimate the mycotoxin levels in these products (n = 76) from four crop regions in Brazil. The results showed high levels of DON and ZEN in the analyzed samples, with contamination levels of 94 and 73.6%, respectively. The mean levels of DON and ZEN ranged from 1700 to 7500 µg/kg and from 300 to 630 µg/kg, respectively. Barley samples from regions 1 and 2 presented higher levels of ZEN and DON, respectively, and those from region 4 presented lower levels of both. Co-occurrence of DON and ZEN was seen in the majority of the barley grain samples, and the mycotoxin content was above the maximum levels established by the Brazilian and European regulations.
Subject(s)
Beer/analysis , Food Contamination/analysis , Hordeum/chemistry , Trichothecenes/analysis , Zearalenone/analysis , Brazil , Chromatography, Liquid , Tandem Mass SpectrometryABSTRACT
Abstract The bats usually inhabit shelters with favorable conditions for fungal proliferation, including pathogenic and opportunistic species. The fungal diversity present on bats is little known and the studies are scarce in Brazil, which only a work has been performed in Cerrado and Pantanal biomes. Therefore, the objective of this study was evaluating the occurrence of filamentous fungi on the rostral region of Molossus molossus in an Atlantic Forest remnant of Brazil. The bats were captured with mist nets installed outside a shelter located in the municipality of Treviso, (28°29'23S and 49°31'23W), south region of state Santa Catarina. With a swab sterile moistened in saline solution, samples from the rostral region were obtained from all captured M. molossus individuals. The samples were taken to the laboratory for analysis and isolation in different culture media, followed of identification of fungal through the microculture technique. In total, 15 individuals were captured, which five fungal genus and 19 taxa were identified. Among the taxa registered, Aspergillioides sp.2, (47%), Penicillium sp.1 (33%), Chrysonilia sp. (33%), Cladosporium sp. (27%) were classified as little constant. In terms of abundance, Penicillium sp.1 (34%), Aspergillioides sp.2 (21%) and Aspergillus sp.2 (11%) were the most abundant in the samples. The results showed the occurrence of high diversity fungal in the rostral region of M. molossus in the Atlantic Forest, which is higher than observed in others Brazilian biomes. Some fungal genera found may harbor pathogenic and opportunistic species that need to be identified for preventing potential disease well as for bat conservation projects.
Resumo Os morcegos comumente abrigam-se em locais com condições favoráveis para proliferação fúngica, incluindo espécies patogênicas e oportunistas. A diversidade fúngica presente nos morcegos é pouco conhecida e os estudos são escassos no Brasil, no qual apenas um trabalho tem sido realizado nos biomas do Cerrado e Pantanal. Portanto, o objetivo deste estudo foi avaliar a ocorrência de fungos filamentosos na região rostral de Molossus molossus em um remanescente da Mata Atlântica no sul do Brasil. Os morcegos foram capturados com redes-de-neblina instaladas na saída de um abrigo localizado no município de Treviso (28°29'23S e 49°31'23W), região sul do estado de Santa Catarina. Com um swab esterilizado e umedecido em solução salina, amostras da região rostral foram obtidas de todos os indivíduos de M. molossus capturados. As amostras foram levadas ao laboratório para análise e isolamento em diferentes meios de cultura, seguido de identificação taxonômica fúngica pela técnica de microcultivo. No total, 15 indivíduos foram capturados, nos quais 5 gêneros fúngicos e 19 taxa foram identificados. Dentre os taxa registrados foram classificados como pouco constante Aspergillioides sp.2, (47%), Penicillium sp.1 (33%), Chrysonilia sp. (33%), Cladosporium sp. (27%). Em termos de abundância, Penicillium sp.1 (34%), Aspergillioides sp.2 (21%) e Aspergillus sp.2 (11%) foram os mais abundantes nas amostras. Os resultados mostraram ocorrência de elevada riqueza de fungos na região rostral de M. molossus na Mata Atlântica, riqueza essa que é superior àquela observada para outros biomas brasileiros. Alguns gêneros fúngicos encontrados podem abrigar espécies patogênicas e oportunistas que precisam ser identificadas tanto para prevenir potenciais doenças, assim como, para os projetos de conservação dos morcegos.
ABSTRACT
Analytical procedure more advanced allowed to identify, to isolate, and assay the compounds present in propoli which is is developed to be a valuable biological product as food resource as medical resource. Analytical procedure more and more sophisticated allowed (us) to assay the propoli composition without operate the derivatization of phenolic constituents making use the capacity of different detector used. These phenolic contents were analysed by capillary gas chromatography using an electron-capture detector. This detector shown a good electron capture response of these compounds, which belong to the so-called "conjugated electrophores".
Subject(s)
Anti-Infective Agents/pharmacology , Propolis/pharmacology , Anti-Infective Agents/chemistry , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Propolis/chemistrySubject(s)
Cross-Cultural Comparison , Electroconvulsive Therapy/trends , Psychotic Disorders/therapy , Adult , Cause of Death , Electroconvulsive Therapy/mortality , Female , Humans , Male , Middle Aged , Patient Care Team/trends , Psychotic Disorders/mortality , Psychotic Disorders/psychology , Treatment Outcome , UruguayABSTRACT
Two multivalent immunotoxins (ITs) with cytotoxic potential against Thy 1.2-expressing tumor cells were used in association with mouse interleukin 2 (IL2) for treatment of mice bearing ascitic EL4 lymphomas. The combined treatment, ITs + IL2, induced an enhanced antitumor effect revealed by a significant prolongation of the survival time of mice as compared to the simple treatment with ITs or IL2 alone. According to the survival of mice treated by combined therapy, the proportion of killed tumor cells rose up to 94% as resulted from the dose-dependent curve of the survival of nontreated mice versus the number of tumor cells inoculated.
Subject(s)
Immunotoxins/therapeutic use , Interleukin-2/therapeutic use , Neoplasms, Experimental/therapy , Animals , Ascites/therapy , Drug Synergism , Immunotoxins/administration & dosage , Interleukin-2/administration & dosage , Mice , Mice, Inbred C57BLABSTRACT
C57BL/6 mice with EL4 leukemia cells in ascitic form were intraperitoneally treated with ricin A chain-multivalent antibody immunotoxins. The immunotoxins containing rabbit IgG anti-Thy 1.2 antibodies complemented by protein A of Staphylococcus aureus were able to interact specifically with the target cells and to induce an antitumor effect as revealed by an increase in survival time of the mice. No apparent secondary effects consecutive to a cytotoxic action on the normal Thy 1.2 antigen bearing cells were observed with the immunotoxin doses used.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Immunotoxins/therapeutic use , Isoantibodies/therapeutic use , Leukemia, Experimental/therapy , Animals , Antibodies, Monoclonal/immunology , Immunotherapy , Isoantibodies/immunology , Male , Mice , Mice, Inbred C57BL , Rosette FormationABSTRACT
The protective role of amrinone against toxicity of anthracyclines was examined in both mice and rats. These two anthracyclines were selected since they are characterized by different patterns of toxicity. In contrast to doxorubicin, the 4'-deoxy derivative did not cause delayed mortality. The results of this investigation indicate that amrinone is an effective protective agent against acute lethal events induced by both anthracyclines. However, the inotropic agent did not reduce the delayed mortality produced by doxorubicin. This parallels the apparent lack of prevention of doxorubicin-induced myocardial toxicity in CD rats, as determined by ECG changes and by morphologic alterations following multiple drug administrations. The administration of amrinone did not interfere with the antitumor activity of 4'-deoxy-doxorubicin against C-26 colon tumor.
Subject(s)
Amrinone/pharmacology , Antibiotics, Antineoplastic/antagonists & inhibitors , Doxorubicin/analogs & derivatives , Doxorubicin/antagonists & inhibitors , Doxorubicin/toxicity , Heart Diseases/prevention & control , Animals , Antibiotics, Antineoplastic/toxicity , Colonic Neoplasms/drug therapy , Electrocardiography , Female , Heart Atria/drug effects , Heart Atria/pathology , Heart Diseases/chemically induced , Heart Diseases/physiopathology , Male , Mice , Mice, Inbred BALB C , Myocardial Contraction/drug effects , Organ Size , RatsABSTRACT
This study assessed the antitumor activity of 1-(2-chloroethyl)-3-/2-(dimethylaminosulfonyl)ethyl-1-nitrosourea (TCNU), a newly soluble nitrosourea, on NMU-1 lung tumor, a transplantable murine model poorly sensitive to BCNU. TCNU delivered orally was more effective after weekly than after biweekly treatments. When TCNU was given weekly intravenously, its therapeutic index was higher than after oral treatment. Compared with BCNU, TCNU showed superior antitumor effects on NMU-1 murine lung tumor. In this experimental model, TCNU activity was comparable to that of drugs active on human lung cancer.
Subject(s)
Lung Neoplasms/drug therapy , Nitrosourea Compounds/therapeutic use , Taurine/analogs & derivatives , Animals , Carmustine/therapeutic use , Male , Mice , Mice, Inbred BALB C , Taurine/therapeutic useABSTRACT
The influence of tumor growth kinetics on response to doxorubicin treatment of C3H mammary carcinoma was investigated. Gompertzian growth curves were obtained for the tumor mass of each mouse by a computerized best fit program. The response was assessed by evaluating: a) the total clonogenic cell reduction as a fraction of the initial tumor volume or the tumor volume that should result at the end of treatment in a free growth condition, and b) the partial clonogenic cell reduction at each drug administration, assuming a first order cell kill hypothesis. Slowly growing tumors at each dose level showed a significantly poorer response than rapidly growing tumors. Each response index exhibited a linear correlation with the specific instantaneous growth rate at the time of treatment. Data also suggested a dose-response dependence.
Subject(s)
Carcinoma/drug therapy , Doxorubicin/therapeutic use , Mammary Neoplasms, Experimental/drug therapy , Animals , Cell Survival , Dose-Response Relationship, Drug , Mice , Mice, Inbred C3HABSTRACT
The main side effect in photodynamic therapy is photosensitization of the patient's skin following systemic administration of the photosensitizing agent. In the case of superficial lesions, this problem can be avoided by topically applying the drug: in this way a local treatment can be performed. We tested the photosensitizing properties of a 2% solution of TPPS (tetrasodium-tetraphenylporphinesulfonate) in a vehicle containing a penetration enhancer, Azone, on skin of nude mice. An aliquot of 0.1 ml/cm2 of the solution was painted on the skin overlying an s.c. implanted NMU-1 tumor. Subsequently, animals were sacrificed at different times after application. Fluorescence microscopy revealed that TPPS penetration depth was related to time elapsed after application and to painting modalities. Solution penetration was enhanced by wiping with ether immediately before painting. Irradiation at 80 mW/cm2 for 20 min with a dye laser emitting at 640 nm, 4 h after TPPS application, produced necrosis of the upper skin layers, up to 0.2 mm in depth. These findings suggest that topical TPPS administration, followed by laser irradiation, may be a suitable treatment modality for skin lesions involving epithelial layers, even though several aspects of this metodology need further investigation.
Subject(s)
Photochemotherapy/adverse effects , Photosensitivity Disorders/chemically induced , Porphyrins/toxicity , Skin/pathology , Adenocarcinoma/drug therapy , Administration, Topical , Animals , Azepines/pharmacology , Male , Mice , Mice, Nude , Necrosis , Photosensitivity Disorders/pathology , Porphyrins/administration & dosage , Porphyrins/therapeutic use , Skin/drug effects , Skin/radiation effects , Skin Neoplasms/drug therapyABSTRACT
Free growth and post-Doxorubicin treatment regrowth of the C3H mammary carcinoma were analysed in individual mice. In both cases, the Gompertzian function provided a better fit than the exponential function, and the difference was statistically significant (P less than 0.001, chi 2 test). No comprehensive Gompertzian function was found, and each individual tumour growth or regrowth was described by a specific curve. Nevertheless, although both individually measured alpha 0 and beta, Gompertzian parameters varied from one animal to another, in both free-growing and post-treatment regrowing tumours a strong linear correlation between alpha 0 and beta was found. A parallelism test was performed to verify if there exists any treatment-induced alteration. The two regression lines appeared to be identical, however.
Subject(s)
Mammary Neoplasms, Experimental/pathology , Animals , Cell Division/drug effects , Doxorubicin/pharmacology , Female , Mathematics , Mice , Mice, Inbred C3H , Models, BiologicalABSTRACT
The purpose of this study was to investigate whether excitation of porphyrin could be related to nonlinear mechanisms of absorption of porphyrin itself or of the medium in which porphyrin is embedded. This possibility was proposed as an explanation for results of previous experiments where a Nd:YAG laser was used. An MS-2 sarcoma transplanted into the hind pad of BALB/c mice was used as the experimental tumor model. Mice were given HpD i.v. (25 mg/kg) 24 h before exposure to light delivered from an IR laser (1,060 nm). Since at dose-rates ranging between 600 and 1,200 mW/cm2 the thermal effect tended to mask the nonlinear effect, the temperature of the limb of mice was kept cold by running water. Irradiation performed under cooling conditions did not show any tumor growth inhibition. Experiments in vitro performed on HT-29 cells by a continuous wave (CW) or pulsed (Q-switch) Nd:YAG laser indicated no appreciable difference in DNA synthesis between irradiated and nonirradiated cells. Our results did not evidence nonlinear mechanisms of absorption by HpD with Nd:YAG laser both in CW and pulsed (nanosecond range) modes. Whether this effect should occur, in any case it is unlikely to be suitable to induce a photodynamic effect due to its low efficiency. Nd:YAG laser could induce a heating related effect, which can improve the therapeutic efficacy of PDT.
Subject(s)
Hematoporphyrins/therapeutic use , Photochemotherapy , Radiation-Sensitizing Agents/therapeutic use , Sarcoma, Experimental/drug therapy , Animals , Hematoporphyrin Derivative , Hindlimb , Light , Mice , Mice, Inbred BALB CABSTRACT
A mixed platinum (II) complex with tert-butylamine and doxorubicin (coordinated via the amino-group) has been synthesized and tested for antitumor activity. The results indicate that the complex was active against doxorubicin-resistant P388 and cisplatin-resistant L1210 leukemias, while maintaining antitumor activity against sensitive parent lines.
Subject(s)
Antineoplastic Agents/chemical synthesis , Doxorubicin/pharmacology , Platinum/pharmacology , Animals , Antineoplastic Agents/pharmacology , Leukemia, Experimental/drug therapy , Mice , Mice, Inbred StrainsABSTRACT
The synthetic polypeptide, poly-L-aspartic acid (PAA, mol. wt = 20,000) has been used as a macromolecular carrier for doxorubicin. The drug may be released in vivo through hydrolysis of the ester linkage formed between the carboxyl groups of the polymer and the drug side chain. PAA has been found to be a suitable carrier since it is a soluble, biodegradable, multivalent and nontoxic polymer. The toxicity and the therapeutic efficacy of free and polymer-linked doxorubicin have been evaluated in normal and tumour-bearing mice, using a variety of experimental tumour systems. In studies on single and multiple drug administration, the results indicated that the polymeric derivative of doxorubicin had approximately 3-fold lower toxicity than did free drug. In addition, the severity of specific toxic effects, including cardio- and vesicant toxicity, were appreciably reduced following conjugation to PAA. The doxorubicin-PAA conjugate gave similar or rather greater therapeutic effects than free drug at less toxic doses. This effect, more evident in the highly sensitive tumours, suggests an improvement of the therapeutic index of the polymer-linked drug.
Subject(s)
Doxorubicin/administration & dosage , Peptides , Animals , Dose-Response Relationship, Drug , Doxorubicin/therapeutic use , Doxorubicin/toxicity , Female , Heart/drug effects , Lung Neoplasms/drug therapy , Male , Mammary Neoplasms, Experimental/drug therapy , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Pharmaceutical Vehicles , RatsABSTRACT
The investigation has been carried out on stimulated and unstimulated peritoneal cavities of rats. China ink and Corynebacterium parvum were injected i.p. both as peritoneal stimuli and markers. Omenta were picked up at time intervals beginning with 10 min and up to seven days after the i.p. injection. The light and electronmicroscopic investigation showed after 10-30 minutes labeled macrophages stuck as monolayers on some peritoneal areas corresponding to the milky spots which developed in size and number. Days after the i.p. injection the labeled macrophages were found deeper in the milky spots. After the fourth day they appeared in the regional lymph nodes. The milky spots contained also large lymphocytes and plasma cells. The results suggest that milky spots are not only places of resident macrophages development and release in the peritoneal cavity but also their exit pathways. Therefore the omentum leads the traffic of peritoneal macrophages. The developed milky spots play also the role of lymphoid structures providing grounds for macrophage-lymphocyte contacts.
Subject(s)
Ascitic Fluid/pathology , Carbon , Macrophages/cytology , Omentum/cytology , Animals , Coloring Agents/pharmacology , Corynebacterium , Microscopy, Electron , Phagocytosis/drug effects , Rats , Rats, Inbred Strains , Staining and Labeling , Time FactorsABSTRACT
The therapeutic efficacy of photoradiation therapy (PRT) following hematoporphyrin derivative (HpD) administration was compared in the experimental MS-2 tumour model to that of conventional treatment methods for local control of neoplastic diseases. The therapeutic effects of PRT and surgical removal of primary tumour were comparable in these experiments. However, optimal effects were critically dependent on the stage of tumour development. In addition, the therapeutic advantage of PRT over radiotherapy suggest an interesting role of a new approach in tumours resistant to this conventional treatment.
Subject(s)
Hematoporphyrins/therapeutic use , Photochemotherapy , Radiation-Sensitizing Agents/therapeutic use , Sarcoma, Experimental/drug therapy , Animals , Cobalt Radioisotopes/therapeutic use , Hematoporphyrin Derivative , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Radioisotope Teletherapy , Radiotherapy, High-Energy , Sarcoma, Experimental/radiotherapy , Sarcoma, Experimental/surgeryABSTRACT
Although the photochemical reaction of hematoporphyrin derivative (HpD) appears to play a major role in cytotoxic activity, the hyperthermal contribution to tumor destruction has not yet been clarified. We investigated its role in the effectiveness of laser photoradiation therapy using MS-2 sarcoma transplanted into the hind pad of BALB/c mice as the experimental model. Mice received HpD i.v., 25 mg/kg - 24 h before exposure to light delivered from a dye laser or Nd-YAG laser, or before warming in a thermostated bath. Since our aim was not to cure the tumor, the treatment response was evaluated only as inhibition of tumor growth at different days after treatment. Our results support the view that in laser photochemotherapy the hyperthermia produced by irradiation and the photodynamic effect mediated by HpD could contribute to tumor destruction. Moreover, a synergistic interaction between the photodynamic effect and heat was observed in this experimental model.
Subject(s)
Hematoporphyrins/therapeutic use , Hot Temperature , Photochemotherapy , Sarcoma, Experimental/radiotherapy , Animals , Combined Modality Therapy , Lasers , Mice , PhototherapyABSTRACT
Daunorubicin was covalently linked to poly-L-aspartic and poly-L-lysine of different molecular weights via the methylketone side-chain of the drug by the use of a method that employs the 14-bromo derivative of the antibiotic. During reaction ester and C-N linkages were formed with poly-L-aspartic acid and poly-L-lysine respectively. Whereas a reduction of drug toxicity was observed with both types of conjugate, only the linking to the anionic polymer produced an enhancement of drug activity. In contrast, when drug was covalently attached to poly-L-lysine, cytotoxic activity and in vivo potency and efficacy were markedly reduced. The different therapeutic properties of these conjugates can be explained in terms of the different nature and stability of chemical bonds formed between the drug and the amino groups and carboxyl functions of the polyamino acid carrier.
