Fusion of small recombinant antibody fragments to an albumin-binding domain (ABD) from streptococcal protein G strongly extends their plasma half-life. This ABD binds with nanomolar affinity to human (HSA) and mouse serum albumin (MSA). It was speculated that an increase in albumin-binding affinity should lead to a further increase in half-life. In the present study, we analyzed the effects of affinity and valency of the ABD on the pharmacokinetic properties of a bispecific single-chain diabody (scDb), applied previously to investigate various half-life extension strategies. The scDb is directed against carcinoembryonic antigen (CEA) and CD3 capable of mediating T cell retargeting to tumor cells. Two scDb derivatives with increased (scDb-ABD-H) and decreased (scDb-ABD-L) affinity as well as an scDb molecule fused to two ABD (scDb-ABD(2)) were generated and produced in mammalian cells. The altered binding of these constructs to HSA and MSA was confirmed by ELISA and quartz crystal microbalance measurements. All constructs bound efficiently to CEA and CD3-positive cells and were able to activate T cells in a target cell-dependent manner, although T cell activation was reduced in the presence of serum albumin. All three derivatives showed a strongly increased half-life in mice as compared with scDb. Compared with the wild-type scDb-ABD, the half-life of scDb-ABD-H exhibited a prolonged half-life and scDb-ABD-L a reduced half-life, while the half-life scDb-ABD(2) was almost identical to that of scDb-ABD. However, these changes were only moderate, indicating that the half-life-extending property of the ABD in mice is only weakly influenced by affinity for serum albumin or valency of albumin binding.

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Solanum lycocarpum, St. Hil (Solanaceae) is a common native shrub in the Brazilian cerrado. The fruits are used in folk medicine as a hypoglycaemic agent in the management of diabetes, obesity and to decrease cholesterol levels. In this study the glycoalkaloids, solamargine and solasonine, were isolated from unripe fruits of S. lycocarpum. To evaluate the effects of the fruits on gestation, pregnant rats (n=25) were fed from day 6 to 22 with chow containing 10% of dried and ground unripe fruits. The control group (n=21) received regular chow. During and after the treatment period the dams showed reduced body weight and slower body weight gain, even with no change in food and water intake, evidencing mild maternal toxicity. Gestation was not significantly impaired, although experimental fetuses presented reduced body length at birth. Also, 20% of the treated dams showed one or two dead pups at birth. On day 22 of gestation and on post-natal day 1, the levels of metabolites of the sex hormones oestradiol, progesterone and testosterone were measured in faeces by radioimmunoassay. On post-natal day 1, tissue portions from the dams were collected for histopathological evaluation. No alterations were detected in either study. The results suggest that S. lycocarpum fruit did not impair gestation, however, it did promote mild maternal toxicity and mild fetotoxic effects if ingested as a food source during the gestation period. This study has implications for pregnant women, who employ phytotherapeutic formulations under the impression that they are harmless.

Phyllanthus niruri L. (Euphorbiaceae), known as "quebra-pedra" (Portuguese for "stonebreaker"), is an herb used for kidney disorders. In light of its frequent use by the population, the present study aimed to investigate the genotoxic, antigenotoxic and cytotoxic activities of a standardized P. niruri extract in bone marrow rats. Three groups of 12 animals were treated daily by gavage over a period of 30 days, with 50, 150 or 250 mg/kg of P. niruri extract aqueous solution. The control group (n = 12) received tap water. At the end of treatment (day 31), groups were divided into two minor subgroups (n=6/group) and received cyclophosphamide (50 mg/kg, i.p.) or saline 0.9% (i.p.). After 24 hours, we evaluated the frequency of micronucleated polychromatic erythrocytes for each animal (MNPCE) at 1000 PCE. Cytotoxicity was evaluated with the PCE/NCE ratio (NEC = normochromatic erythrocytes). General toxicity was assessed during treatment using the parameters of body weight gain, ration and water consumption. The dry extract did not provoke changes in body weight, weight gain, ration and water intake or changes in the frequency of MNPCE or cytotoxicity in bone marrow. We propose that the P. niruri extract used here showed no genotoxic, antigenotoxic and cytotoxic activities under the experimental conditions. Uniterms: Phyllanthus niruri L./genotoxicity. Phyllanthus niruri L./toxicological analysis/experimental study. Medicinal plantas/evaluation.Phyllanthus niruri L. (Euphorbiaceae), conhecida como "quebra-pedra", é uma planta medicinal utilizada frequentemente pela população no tratamento de problemas renais. Foram avaliadas as atividades genotóxicas, antigenotóxicas e citotóxicas de um extrato padronizado dessa espécie em ratos. Três grupos de doze animais foram tratados durante trinta dias, por gavagem, com 50, 150 ou 250 mg/kg/dia de solução aquosa do extrato de P. niruri e um grupo controle (n=12) recebeu água destilada pela mesma via. No final do tratamento os grupos foram divididos em dois subgrupos (6 animais/grupo) e receberam uma dose única de ciclofosfamida (50 mg/kg, i.p.) ou de solução salina 0,9% (i.p.). Após 24 horas, a frequência de eritrócitos policromáticos micronucleados (EPCMN) foi avaliada em 1000 EPC. A citotoxicidade foi avaliada pela relação entre eritrócitos policromáticos e normocromáticos (EPC/ ENC) e a toxicidade geral foi avaliada através dos parâmetros de ganho de peso corporal, consumo de ração e ingestão hídrica. O extrato seco não provocou alterações significativas no peso corporal, ganho de peso e consumo de ração em relação ao grupo controle, nem alterações na frequência de EPCMN ou citotoxicidade em medula óssea. Dessa maneira, pode-se concluir que P. niruri não apresentou atividades genotóxica, antigenotóxica e/ou citotóxica nas condições experimentais executadas. Unitermos INTRODUCTIONMedicinal plants and their preparations have been used to treat several illnesses since the dawn of human history and are one of the foundations for healthcare worldwide (AESGP, 1998;Turolla, 2004;Me...

Human chorionic gonadotropin (hCGβ) values were determined in the blood of 19 women and 4 men on maintenance hemodialysis. Blood samples were taken 3 times at an interval of 1 week. Measurements were done by an hCGβ RIA kit (Serono). The median hCGβ values were 9 mlU/ml (range 0–116) in 7 menstruating women, 6 (0–25) in 11 postmenopausal women and 0 (0–7) in 4 men. There was no statistically significant difference between the 3 groups. The median hCGβ values in all 3 groups were below the upper normal limit. However, the individual measurements varied considerably with elevation in 32% of 52 measured values (10-fold elevation in 2 cases). We conclude that in the blood of non-pregnant women on chronic hemodialysis, elevated hCGβ values can be found, erroneously indicating an intact pregnancy of 3–5 weeks duration or a nonintact pregnancy (e.g. impending abortion, extrauterine gravidity).