Determination of cyanide in whole seeds and brans of linseed (Linum usitatissimum Linn) by molecular spectrophotometry

Abstract The addition of linseed (Linum usitatissimum Linn) in the diet, as a functional food, has increased over the years. However, it possesses cyanogenic glycosides. This study aimed to quantify and compare cyanide concentration in whole seed and bran of brown and golden types to establish a safe limit of intake. Three commercial labels, from brown and golden whole seed types (Ab, Ag, Bb, Bg, Cb and Cg), and six commercial labels of brown and golden bran (1b, 2g, 3g, 4b, 5g, and 6b), were selected, totalizing twelve samples. Total cyanide concentration was quantified by a colorimetric method employing alkaline picrate, after acid hydrolysis. The whole seed cyanide values were between 348.4 and 473.20 µg/g and the bran cyanide values were between 459.53 and 639.35 µg/g. The analyzed bran presented increased cyanide concentrations than the whole seeds with no differences between brown and golden types. Food able to produce cyanide less than 90 µg/kg body weight, daily, is considered secure for consumption. Considering this limit and analyzed samples, it is safe to eat approximately two tablespoons of seeds or one tablespoon of bran. These results point out the importance of cyanide amount daily intake information to be in linseed packaging, to ensure secure consumption

Outcome after bilateral deep vein thrombosis.

Background: The aim of our study was to assess how often deep vein thrombosis (DVT) occurs bilaterally and if this has an impact on the recurrence rate of thromboembolic disease and on the occurrence of malignant tumors. Additionally, the occurrence of pulmonary embolism and mortality of patients was assessed. Patients and methods: For this observational study, we retrospectively screened all patient's records for DVT, investigated between 2000 and 2017. 2409 patients with the diagnosis of DVT were found. The patients aged between 18 and 89 years old in 2017, received a follow-up questionnaire, asking for thromboembolic recurrence, malignant tumors and pulmonary embolism. 755 patients were included in the follow-up cohort (604 with unilateral, 151 with bilateral DVT). We performed nonparametric tests to assess two group analysis. Results: Bilateral DVT occurred in 19% of the patients in this cohort. Patients with bilateral DVT develop significantly more often cancer, either at the time of diagnosis or in the follow up, compared to patients with unilateral DVT (22.5% vs. 15.4%, p=0.036). They also endure significantly more often pulmonary embolism simultaneously (33.8% vs. 20.8%, p<0.001). Patients with bilateral DVT were significantly older (median 69 years) than patients with unilateral DVT (median 63 years, p<0.001). In addition, patients with bilateral DVT show a higher mortality (9.1% vs. 5.2%, p=0.002), a higher recurrence rate could not be observed. Conclusions: Bilateral DVT is more common than published so far. Patients with bilateral DVT suffer more often from malignant tumors, and are more often diagnosed with pulmonary embolism. The patients with bilateral DVT are older and have a higher mortality. Further investigations should address the issue of recurrent thromboembolic disease in a prospective cohort study.

Genotoxicity and pharmacokinetic characterization of Cereus jamacaru ethanolic extract in rats.

The effect of Cereus jamacaru ethanolic extract in rats was analyzed using genotoxicity assays and liver ABCB1 and CYP2D4 gene expression. The lyophilized extract of C. jamacaru cladodes was analyzed with LC-MS/MS. Male Wistar rats (n=36) were equally distributed into six groups that did (+) or did not (-) receive cyclophosphamide treatments: Control (-); Control (+); EXP 1 (-), and EXP 1 (+), both treated with 210 mg/kg of ethanolic extract; and EXP 2 (-) and EXP 2 (+), both treated with 420 mg/kg of ethanolic extract. After 30 d of treatment, body weight and food and water intake were monitored. Right femur of the rats and spinal canal fluid were harvested and used for genotoxicity assays, and the liver samples were used for gene expression studies. The phytochemical analysis identified novel compounds. Animals treated with C. jamacaru showed lower body weight and food ingestion compared to controls (P<0.05). The genotoxicity assay showed an absence of ethanolic extract cytotoxicity. CYP2D4 expression was higher in EXP 2 groups compared with EXP 1 (-) group (P<0.05). ABCB1A expression was higher in negative groups compared with the positive groups. These results indicated a new phytochemical characterization of C. jamacaru and its effect on food ingestion and body weight gain. Moreover, the genotoxicity assay suggested that C. jamacaru ethanolic extract treatment presents significant intrinsic genotoxic potential and the enhanced expression of ABCB1 and CYP2D4 on C. jamacaru extract treatment suggests a role of the efflux transporter and microsomal enzyme, respectively, in C. jamacaru pharmacokinetics.

Diurnal Fluctuations of Verticality Perception - Lesser Precision Immediately after Waking up in the Morning.

Internal estimates of direction of gravity are continuously updated by integrating vestibular, visual and proprioceptive input, and prior experience about upright position. Prolonged static roll-tilt biases perceived direction of gravity by adaptation of peripheral sensors and central structures. We hypothesized that in the morning after sleep, estimates of direction of gravity [assessed by the subjective visual vertical (SVV)] are less precise than in the evening because of adaptation to horizontal body position and lack of prior knowledge about upright position. Using a mobile SVV-measuring device, verticality perception was assessed in seven healthy human subjects on 7 days in the morning immediately after waking up and in the evening while sitting upright. Paired t-tests were applied to analyze diurnal changes in SVV trial-to-trial variability. Average SVV variability in the morning was significantly larger than in the evening (1.9 ± 0.6° vs. 0.9 ± 0.3°, p = 0.002). SVV accuracy was not significantly different (-1.2 ± 0.9° vs. -0.4 ± 0.4°, morning vs. evening, p = 0.058) and was within normal range (±2.3°) in all but one subject. A good night's sleep has a profound effect on the brain's ability to estimate direction of gravity. Resulting variability was significantly worse after waking up reaching values more than twice as large as in the evening while there was no significant impact on SVV accuracy. We hypothesize that lacking prior knowledge, adaptation of peripheral sensors, and lower levels of arousal and cerebral metabolism contribute to such impoverished estimates. Our observations have considerable clinical impact as they indicate an increased risk for falls and fall-related injuries in the morning.

Oral exposure to cylindrospermopsin in pregnant rats: reproduction and foetal toxicity studies.

Cylindrospermopsin (CYN) induces toxicity in pregnant mice when administered intraperitoneally. This study investigated whether oral exposure to CYN (0.03, 0.3 and 3 µg/kg) during pregnancy causes toxic effects and impairs gestation in rats. The results of reproductive performance and teratology studies were similar between the control and experimental dams. Our findings suggest that CYN consumption within the guideline values for drinking water is not able to promote foetal toxicity or alterations in rat reproductive performance.

Evaluation of (anti)genotoxic activities of Phyllanthus niruri L. in rat bone marrow using the micronucleus test

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.

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.

Antioxidant activity and protective effect of Turnera ulmifolia Linn. var. elegans against carbon tetrachloride-induced oxidative damage in rats.

The present study aimed to determine whether the leaves of Turnera ulmifolia Linn. var. elegans extract exert significant antioxidant activity. The antioxidant activity of its hydroethanolic extract (HEETU) was evaluated by assessing (a) its radical scavenging ability in vitro, and (b) its in vivo effect on lipid peroxidation and antioxidant enzyme activities. The in vitro antioxidant assay (DPPH) clearly supported HEETU free radical scavenging potential. Moreover, glutathione content and antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase and catalase) were significantly enhanced in CCl(4)-treated rats due to oral HEETU-treatment (500 mg/kgb.w.) over 7 and 21 days. In addition, an improvement was observed in lipid peroxidation and serum biochemical parameters (aspartate aminotransferase and alanine aminotransferase), indicating a protective effect against CCl(4)-induced liver injuries, confirmed by histopathological studies. The HEETU effect was comparable to the standard drug Legalon® (50 mg/kgb.w.) under the same experimental condition. Quantitative analysis of the HPLC extract revealed the presence of flavonoids, wich mediate the effects of antioxidant and oxidative stress. In conclusion, extract components exhibit antioxidant and hepatoprotective activities in vitro and in vivo.

Production of bispecific antibodies: diabodies and tandem scFv.

Recombinant bispecific antibodies have many different applications; especially promising is their therapeutic potential due to their ability to retarget an effector molecule or a cell to a disease-related target structure. In the last years, many formats have been developed: two commonly used are the bispecific diabody and the tandem scFv. In this chapter, the cloning, bacterial production, purification, and characterization of the two antibody formats are described in detail.

Embryo and fetal toxicity of Mentha x villosa essential oil in Wistar rats.

CONTEXT: Mentha x villosa Hudson (Lamiaceae) is an aromatic herb employed as a food spice. In folk medicine, it leaves are used as a tranquilizer and anti-hypertensive, even by pregnant women. OBJECTIVE: There are no reports about its effects in gestation and exposed fetuses, the aim of this study. MATERIALS AND METHODS: At gestation day (GD) 01, 24 rats were divided in four groups: one control and three experimental groups (n = 6/group). The experimental groups received, by gavage, from GD06 to GD16, 10, 25 or 50 µg/kg/day of Mentha x villosa essential oil. The control group received the vehicle (Tween 80 and distilled water--2%). The parameters of body weight gain, water and food intake were recorded. At GD20 the females were euthanized. Half of the fetuses from each litter were directed for the study of visceral malformations and the remaining fetuses for the study of skeletal malformations. RESULTS: The statistical analyses revealed absence of alterations in body weight gain, water and food intake, litter weight, fetuses number and weight, reabsorptions and implantations. The treatment revealed absence of visceral and skeletal malformations. The visceral analysis revealed mild hemorrhagic points at brain, but more numerous at kidney, liver and blood vessels near heart, in some fetuses from some experimental litters. CONCLUSION: The essential oil was not able to promote impairment to the pregnant rats and to gestation. Even occurring lack of malformations, fetotoxicity was revealed by mild hemorrhagic points at liver, kidney, brain and blood vessels of some exposed fetuses.

Half-life extension of a single-chain diabody by fusion to domain B of staphylococcal protein A.

Binding of a therapeutic protein to a long-circulating plasma protein can result in a strongly extended half-life. Among these plasma proteins, albumin and immunoglobulins are of special interest because of their exceptionally long half-life, which is to a great extent determined by recycling through the neonatal Fc receptor (FcRn). Many strategies have been established employing reversible binding to albumin, e.g. using an albumin-binding domain from streptococcal protein G. We show here that the half-life of a recombinant antibody molecule can also be prolonged by fusion to a single immunoglobulin-binding domain (IgBD) from staphylococcal protein A. This domain (domain B, SpA(B)) is composed of 56 amino acid residues and was fused to the C-terminus of a bispecific single-chain diabody (scDb). The scDb-SpA(B) fusion protein was produced in HEK293 cells and retained its antigen-binding activity as shown by enzyme-linked immunosorbent assay and flow cytometry. Furthermore, the fusion protein was capable of binding to human and mouse IgG in a pH-dependent manner. In mice, the terminal half-life of the fusion protein was improved from ∼1-2 h of the unmodified scDb to 11.8 h. Although the fusion protein did not reach the long half-life seen for IgG, our results established the applicability of a single bacterial IgBD for half-life extension purposes.

Plasma half-life extension of small recombinant antibodies by fusion to immunoglobulin-binding domains.

Many therapeutic proteins possessing a small size are rapidly cleared from circulation. Half-life extension strategies have therefore become increasingly important to improve the pharmacokinetic and pharmacodynamic properties of protein therapeutics. Here, we performed a comparative analysis of the half-life extension properties of various bacterial immunoglobulin-binding domains (IgBDs) derived from Staphylococcus protein A (SpA), Streptococcus protein G (SpG), and Finegoldia (formerly Peptostreptococcus) protein L (PpL). These domains, composed of 50-60 amino acid residues, were fused to the C terminus of a single-chain Fv and a bispecific single-chain diabody, respectively. All fusion proteins were produced in mammalian cells and retained their antigen-binding properties. The half-lives of the antibody molecules were prolonged to varying extents for the different IgBDs. The strongest effects in mice were observed for domain C3 of SpG (SpG(C3)) followed by domains B and D of SpA, suggesting that SpG(C3) is particularly useful to extend the plasma half-life of small proteins.

The effects of affinity and valency of an albumin-binding domain (ABD) on the half-life of a single-chain diabody-ABD fusion protein.

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.

Evaluation of Bauhinia monandra aqueous and ethanol extracts in pregnant rats.

Bauhinia monandra Kurz. (Fabaceae: Caesalpinioideae) is a plant widely employed in Brazilian folk medicine for hypoglycemia. However, little is known about the effect of maternal exposure to this plant on fetal development. The aqueous and ethanol extracts obtained from B. monandra dried leaves were administered to pregnant Wistar rats throughout gestation (day 1 to day 20) at 1,400 or 7,000 mg/kg/day (n = 6/group). Maternal toxicity was not observed in the dams of both groups, and was evaluated by observing body weight, water and food intake during treatment, by measuring serum biochemical levels of creatinine, urea, AST and ALT, and by studying the histopathology of liver, kidney, pancreas, spleen and uterus at the end of treatment (gestation day 20). Both extracts and doses did not impair reproductive performance or delay fetal development, measured by observing implantations and reabsorptions in the uterus, by counting the number of corpora lutea in ovaries, by recording the litter weight and number of live and dead fetuses and by analyzing possible skeleton and viscera malformations in the fetuses. Also, the aqueous extract promoted decreased post-implantation loss when compared to the control group. The aqueous and ethanol extracts from B. monandra dried leaves (1,400 or 7,000 mg/kg/day) did not cause maternal or fetal toxicities and the aqueous extract promoted increased implantation and decreased post-implantation loss in the pregnant rats.

Toxicological evaluation of 10% Solanum lycocarpum St. Hill fruit consumption in the diet of growing rats: hematological, biochemical and histopathological effects.

Solanum lycocarpum St. Hill (Solanaceae) is a native shrub very common in the Brazilian savanna. The fruit of this plant contains steroidal glycoalkaloids that may disrupt the endocrine system. Because this plant is employed in folk medicine for the management of diabetes, obesity and decreasing cholesterol levels, the present study determined the possible toxic effects of exposure to S. lycocarpum fruit from weaning (21 days old) until adult age (8 weeks of treatment) in male and female rats. In male rats, the plant reduced weight gain, while few significant differences were observed in female animals. Slight significant differences were observed in food and water consumption and in hematological parameters in treated rats. Reductions in adrenal gland, spleen, heart, kidneys and thymus weights of treated males were observed, while increased relative weights were detected in the heart, epididymises, lungs, seminal vesicles, and testicles. In females, no differences were observed in organ weights and few differences were observed in relative weights of some organs. The histopathologic study showed no alteration between groups. Serum biochemical parameters showed triglyceride reductions in treated animals of both sexes; in females, an increase in albumin and alanine aminotransferase levels and a reduction in total protein levels were noted. The present data therefore demonstrate sex-related differences in S. lycocarpum toxicity.

Avalação de efeitos toxicológicos e comportamentais da Hypericum perforatum e da Pipe methysticum em ratos / Hypericum perforatum and Piper methysticum are phytotherapics frequently employed for the treatment of mild to moderate central nervous system depression

There is no conclusive information in literature about the adverse side effects in human health. The aim of this study was to assess if these phytotherapics can promote toxic and/or behavioral alterations in rats. Adult male Wistar rats (17) were randomly divided into three groups. Two experimental groups (n=6) were treated by gavage with an aqueous solution obtained from commercial extracts of H. perforatum (15 per cent m/v - 2 mg/kg/day of hypericine) or P. methysticum (7.5 per cent m/v - 85.7 mg/kg/day of kavapirones). The control group (n=5) received only water by gavage. At day 31 the animal behavior was analyzed in the open field, elevated plus-maze and employing the forced swimming test. The animals were sacrificed for serum and tissues samples collection, allowing the biochemical and histopathological studies. The statistical analysis employed revealed no behavioral changes and absence of alterations at the parameters body weight gain, foodand water intake, ALT, AST, urea and creatinine serum levels, and in the histopathological study. The data obtained show that rats treated with the respective plants aqueous solutions, did not present behavioral alterations or toxic effects.

As ervas Hypericum perforatum e Piper methysticum são frequentemente empregadas no tratamento de depressões leves a moderadas. O presente trabalho objetivou analisar efeitos tóxicos e alterações comportamentais desses fitoterápicos em ratos. Foram utilizados 17 ratos machos Wistar adultos, separados em três grupos: controle (n=5) e experimentais (n=6/grupo). Os animais experimentais receberam, por gavagem, soluções aquosas de H. perforatum (15 por cento m/v) contendo 2 mg/kg de hipericina, ou de P. methysticum (7,5 por cento m/v) contendo 85,7 mg/kg de kavapironas, diariamente durante 30 dias. Um dia após término do tratamento, os animais tiveram o comportamento avaliado no campo-aberto, no labirinto em cruz elevado e pelo emprego do teste da natação forçada. Em seguida, os animais foram submetidos à eutanásia para a coleta de amostras de sangue e tecidos para estudos bioquímicos e histopatológicos. A análise estatística dos dados indicou que as soluções aquosas empregadas não foram capazes de promover alterações comportamentais nem toxicidade, por não terem sido observadas alterações nos parâmetros ganho de peso, ingestão hídrica, consumo de ração, níveis séricos de ALT, AST, uréia e creatinina, e no estudo histopatológico. Portanto, o presente trabalho sugere que os fitoterápicos, nas dosagens e tempo de administração, empregados não foram capazes de causar toxicidade e alterações comportamentais em ratos.

Reproductive alterations in male rats exposedperinatally to Solanum lycocarpum fruits / Alterações reprodutivas em ratos machos expostos perinatalmente aos frutos da Solanum lycocarpum

This work employed pregnant rats treated with Solanum lycocarpum unripe fruits (10% in diet) from gestation day (GD) 06 to post-natalday (PND) 07, for the evaluation of the sperm number, daily sperm production and epididymal sperm transit time of the male offspring at PND 60 and PND 90. No differences were observed in the daily sperm production (DSP) and sperm number in the testis of the exposed males at PND 60 and PND 90. Also, no alterations were observed in sperm transit time in the caput epididymis of the exposed males at PND 60 and PND 90. However, a reduced sperm transit time was observed in the corpus/cauda epididymis of the experimental males at PND 90. The last data may explain the reduced sperm number observed in the corpus/cauda epididymis of the experimental male rats at PND 90. These data show that the male rats exposed to S.lycocarpum fruits during gestation did not present alterations in testis sperm production and number, however the sperm transit time through epididymis was impaired, resulting in a decreased number of spermatozoa in epididymis cauda. We conclude that S. lycocarpummay cause imbalance on hypothalamus-pituitary gland axis

Ratas prenhes foram tratadas do dia 06 da gestação (GD 06) ao dia 07 pós-natal (PND 07) com frutos verdes secos e moídos da Solanum lycocarpum (10% na ração). Após nascimento das ninhadas, foi avaliado na prole masculina adulta aos 60 e 90 dias de vida, o número de espermátides e a produção espermática diária nos testículos e o tempo de trânsito espermático no epidídimo. A exposição não foi capaz de promover alterações na produção espermática diária (DSP) e no número de espermátides produzidas pelo testículo dos ratos expostos aos frutos verdes da S. lycocarpum durante a gestação e início da lactação. Não foram observadas alterações no tempo de trânsito espermático na cabeça do epidídimo, porém, foi constatado menor número de espermatozóides no corpo/cauda do epidídimo nos machos experimentais com 90 dias de vida, provavelmente resultante do menor tempo de trânsito espermático observado no corpo/cauda do epidídimo aos PND 90. Estes dados sugerem que a exposição de ratos aos frutos verdes da S. lycocarpum durante a gestação e início dalactação, não foi suficiente para promover alterações na produção mas sim no trânsito espermático, indicando possível alteração no eixo hormônio liberador das gonadotrofinas hipotálamo-hipófise-gônada

Phytochemical study of Solanum lycocarpum (St. Hil) unripe fruit and its effects on rat gestation.

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.

Rats offspring exposed to Ipomoea Carnea and handling during gestation: neurochemical evaluation

The present study evaluated the central monoamine levels of male and female adult rat offspring exposed orally by gavage to 0.0, 0.7, 3.0 and 15.0 mg/kg I. carnea aqueous extract daily, from gestation day (GD) 5 to GD 21. Several alterations in the monoamine activity systems were observed. However, the major differences were noted between the 0.0 mg/kg and the no gavage control groups, showing that alterations showing that alterations were not due to the alterations to the aqueous extract. The control data showed that gavage and handling of dams were stressful enough to produce a significant decline in 3,4-dihydroxyphenylacetic acid (DOPAC) and an increase in vanilmandelic acid (VMA), indicating decreased dopamine (DA) and enhanced norepinephrine (NE) activity, respectively.

Estudo anterior realizado em filhotes de ratas tratadas diariamente por gavage com 0,0, 0,7, 3,0 e 15,0 mg/kg de uma solução aquosa obtida de folhas frescas da Ipomoea carnea, do dia 5 ao dia 21 da gestação, mostrou poucas alterações comportamentais na prole em vida adulta. O presente estudo teve como objetivo avaliar a atividade e níveis das monoaminas cerebrais nas proles masculina e feminina expostas ao mesmo tratamento acima descrito. As maiores alterações encontradas, entretanto, foram entre os grupos 0,0 mg/kg e controle negativo (no gavage), impedindo a atribuição das alterações encontradas à solução aquosa. O dados resultantes do grupo controle sugerem que o estresse provocado pela gavage e pelo manuseio das fêmeas enquanto prenhes é suficiente para produzir um importante declínio nos níveis do ácido 3,4 dihidroxifenilacético (DOPAC) e um não menos importante aumento nos níveis do ácido vanilmandélico (VMA), promovendo maior atividade do sistema noradrenérgico (NE).

Impaired female sexual behavior of rat offspring exposed to Solanum lycocarpum unripe fruits during gestation and lactation: lack of hormonal and fertility alterations.

Solanum lycocarpum St. Hil (Solanaceae) is an invasive and native shrub very common in the Brazilian savanna. It is well known that this plant contain steroidal glycoalkaloids that can be transformed into an intermediate for steroidal drugs production, like oral contraceptives. In this way, it is very possible that these glycoalkaloids and its aglycone, once in the body by ingestion of S. lycocarpum fruits, may act disrupting to the endocrine system. Rat offspring were exposed to S. lycocarpum unripe fruits (10% in the diet) from gestational day (GD) 06 to post-natal day (PND) 07. The female exposed offspring showed, at adult age (PND 100), impaired sexual behavior. However, the fecal hormonal metabolite levels, measured at PND 30, PND 60 and PND 90, and the fertility (PND 120) of male and female experimental offspring were normal. We can assume that the steroidal glycoalkaloids, solamargine and solasodine, present in the fruit, are degradated, once inside the organism, to the steroidal alkaloid solasodine, which may penetrate, by simple diffusion, the placental and/or the hematoencephalical barriers and impact the fetuses. Finally, S. lycocarpum fruit may act as phytohormones, promoting perhaps some neural alterations that at adult age may impair the sexual behavior of the experimental female without impairing the fertility and sexual hormone synthesis. These changes observed can be the direct consequence of the toxic actions of the steroidal alkaloid on the female offspring during fetal development.

Homeopatia no Sistema Único de Saúde

Diante da realidade atual da Homeopatia no Sistema Único de Saúde (SUS), o presente trabalho visa retratar o atendimento homeopático, o perfil do paciente, as formas medicamentosas mais receitadas, o grau de abandono do tratamento, a duração do tratamento e forma de aquisição dos medicamentos pelos pacientes atendidos em ambulatórios do SUS do Estado de São Paulo [...] Todos os pacientes entrevistados na cidade de São Paulo disseram acreditar na Homeopatia. Já na região de Botucatu, 28,6% dos pacientes entrevistados disseram não acreditar na Homeopatia, possivelmente pelo fato de apenas 52% destes terem utilizado a Homeopatia. Além disso, apenas 43% dos entrevistados em Botucatu foram atendidos pelo SUS, enquanto que 75% dos pacientes entrevistados em São Paulo foram atendidos pelo sistema público. A grande maioria dos pacientes entrevistados em São Paulo continuam empregando a Homeopatia como forma de tratamento das enfermidades. Já em Botucatu a grande maioria dos pacientes que já fizeram uso do medicamento homeopático não empregam mais a Homeopatia para tratar suas enfermidades. Adicionalmente, enquanto 100% dos pacientes entrevistados em São Paulo disseram utilizar e recomendar a Homeopatia, apenas 57% dois entrevistados em Botucatu disseram recomendar o tratamento e apenas 48% disseram empregar a Homeopatia para o tratamento de enfermidades. Uma possível falha na atenção médica homeopática na região de Botucatu, pode ser aqui sugerida. Certamente os tratamentos não são levados adiante não por desinteresse ou descaso do paciente, mas sim pelas dificuldades enfrentadas pela equipe de saúde da região. De um modo geral, é importante que a equipe homeopática do SUS de São Paulo e Botucatu se empenhem em eclarecer as dúvidas dos pacientes quanto ao conceito da Homeopatia e em adquirir recursos para que o medicamento homeopático seja oferecido gratuitamente ao paciente.