Dandelion-enriched diet of mothers alleviates lead-induced damages in liver of newborn rats.

Lead (Pb) is a highly toxic metal present in the environment. It causes disturbances of several functions, including hematologic, renal, reproductive and nervous ones. Preventive or curative use of medicinal plants against these disorders may be a promising and safe therapeutic strategy. This study evaluated the hepatic toxic effects of prenatal exposure to lead in rats and the possible protective effect of dandelion (Taraxacum officinale) added to the diet. Female rats were given a normal diet (control) or a diet enriched with dandelion (treated). In addition, lead acetate was administered to half of the rats through drinking water from the 5th day of gestation until the 14th day postpartum. Lead toxicity was evaluated in their offspring by measuring body and liver weights, plasma biochemical parameters, liver damage, as well as protein content and activities of antioxidant enzymes in the liver tissues. Lead poisoning of mothers caused lead deposition in blood and stomach of their pups as well as hepatic tissue damages. Moreover, significant decreases in liver weight and protein content were found. Lead treatment caused oxidative stress and marked changes in the activity of antioxidant enzymes. However, no damages or biochemical changes were observed in puppies from the rats co-treated with lead and dandelion. These results indicate that supplementation of pregnant and lactating rats with dandelion protects their offspring against lead poisoning, likely through reduction of oxidative stress and liver damages.

Methyl thiophanate-induced toxicity in liver and kidney of adult rats: a biochemical, molecular and histopathological approach.

The aim of this study was to elucidate the redox effects of Thiophanate methyl (MT) in the rat liver and kidney. Our results showed, after 3 days of MT injection (700 mg/kg), an increase in malondialdehyde (MDA), hydrogen peroxide and advanced oxidation protein products levels. Glutathione peroxidase and superoxide dismutase activities were also remarkably increased in the liver but decrease in the kidney. Glutathione and vitamin C values were significantly reduced. The changes in biochemical parameters were substantiated by histological and molecular data. A smear without ladder formation on agarose gel was shown, indicating random DNA degradation in the liver and the kidney of MT treated rats. The increase in cyclooxygenase-2 gene expression, marker of inflammation, and an increase in genes expression of glutathione peroxidase and superoxide dismutase in liver and their decrease in the kidney were also occurred after MT exposure. These data confirmed the pro-oxidant and genotoxic effects of this fungicide.

Spirulina exhibits hepatoprotective effects against lead induced oxidative injury in newborn rats.

Lead is a toxic metal that induces a wide range of biochemical and physiological effects. The present investigation was designed at evaluating the toxic effects of a prenatal exposure to lead of mothers on hepatic tissue of newborn rats, and potent protective effects of spirulina. Female rats were randomly divided into 4 groups which were given a normal diet (control),a diet enriched with spirulina (S), lead acetate administered through drinking water (Pb), or a diet enriched with spirulina and lead contaminated water (S Pb), respectively. The duration of treatments was from the 5th day of gestation to 14 days postpartum. Lead toxicity was assessed by measuring body and liver weights, blood and stomach lead levels, hepatic DNA, RNA and protein amounts, blood enzyme activities (AST and ALT), as well as lipid peroxidation level and activities of antioxidant enzymes in hepatic tissues of neonates. Lead intoxication of mothers caused reduction of liver weight as well as of hepatic DNA, mRNA and protein levels in newborns. Moreover, oxidative stress and changes in antioxidant enzyme activities were recorded. Conversely, supplementation of mothers with spirulina mitigated these effects induced by lead. These results substantiated the potential hepatoprotective and antioxidant activity of spirulina.

Ameliorative effects of vanillin on potassium bromate induces bone and blood disorders in vivo.

The objective of this study was to investigate the propensity of potassium bromate (KBrO3) to induce oxidative stress in blood and bone of adult mice and its possible attenuation by vanillin. Our results demonstrated, after KBrO3 treatment, a decrease of red blood cells and hemoglobin and a significant increase of white blood cell. A decrease in plasma levels of folic acid, vitamin B12 and iron was also noted. Interestingly, an increase of lipid peroxidation, hydroperoxides, hydrogen peroxide, advanced oxidation protein products and protein carbonyl levels in erythrocytes and bone was observed, while superoxide dismutase, catalase and glutathione peroxidase activities and glutathione, non-protein thiol and vitamin C levels were decreased. KBrO3 treatment resulted in blood and bone DNA fragmentation, a hallmark of genotoxicity-KBrO3-induced, with reduction of DNA levels. Calcium and phosphorus levels showed a decrease in the bone and an increase in the plasma after KBrO3 treatment. These biochemical alterations were accompanied by histological changes in the blood smear and bone tissue. Treatment with vanillin improved the histopathological, hematotoxic and genotoxic effects induced by KBrO3. The results showed, for the first time, that the vanillin possesses a potent protective effect against the oxidative stress and genotoxicity in bone and blood of KBrO3-treated mice.

Biological activities and wound healing potential of a water-soluble polysaccharide isolated from Glycyrrhiza glabra in Wistar rat.

The present study aimed to evaluate the in vitro antibacterial and antioxidant activities and the in vivo wound healing performance of a polysaccharide isolated from Glycyrrhiza glabra named PSG. It was structurally characterized by Fourier transformed infrared (FT-IR) spectroscopy, which confirmed the presence of different polysaccharides functional bands. The antioxidant capacity of PSG was determined in vitro and evaluated in vivo through the examination of wound healing capacity. Thirty two rats were randomly divided into four groups: group I was treated with physiological serum (negative control); group II was treated with "CYTOL CENTELLA®"; group III was treated with glycerol and group IV was treated with polysaccharide. The response to treatments was assessed by macroscopic, histologic, and biochemical parameters. Data revealed that our sample exhibited potential antioxidant activities and accelerated significantly the wound healing process, after ten days of treatment, proved by the higher wound appearance scores and a higher content of collagen confirmed by histological examination, when compared with control and "CYTOL CENTELLA®". Overall, these findings proved that this polysaccharide isolated from Glycyrrhiza glabra could be considered as a natural bioactive polymer for therapeutic process in wound healing applications.

Recombinant human erythropoietin prevents etoposide- and methotrexate-induced toxicity in kidney and liver tissues via the regulation of oxidative damage and genotoxicity in Wistar rats.

Etoposide (ETO) and methotrexate (MTX) are two effective chemotherapeutic drugs. However, the clinical use of these drugs is limited by its toxicity in normal tissues, especially in kidney and in liver tissues. Recombinant human erythropoietin (rhEPO), erythropoietin hormone, has also been shown to exert tissue protective effects. The purpose of this study was to explore the protective effect of rhEPO against oxidative stress and genotoxicity induced by ETO and MTX in vivo. Adult male Wistar rats were divided into 10 groups (6 animals each): control group, rhEPO alone group, ETO alone group, MTX alone group and rhEPO + ETO/MTX groups. In rhEPO + ETO/MTX groups, three doses of pretreatment with rhEPO were performed: 1000, 3000 and 6000 IU/kg. Our results showed that rhEPO pretreatment protects liver and kidney tissues against oxidative stress induced by the anticancer drugs. The glycoprotein decreased malondialdehyde (MDA) levels, reduced catalase activity and ameliorated glutathione depletion. Furthermore, we showed that rhEPO administration prevented drug-induced DNA damage accessed by comet test. Altogether, our results suggested a protective role of rhEPO, especially at 3000 IU/kg, against ETO- and MTX-induced oxidative stress and genotoxicity in vivo.

LC-MSMS identification of Arabidopsis thaliana heat-stable seed proteins: enriching for LEA-type proteins by acid treatment.

Protein identification in systems containing very highly abundant proteins is not always efficient and usually requires previous enrichment or fractionation steps in order to uncover minor proteins. In plant seeds, identification of late embryogenesis abundant (LEA) proteins is often masked by the presence of the large family of storage proteins. LEA-proteins are predicted to play a role in plant stress tolerance. They are highly hydrophilic proteins, generally heat-stable, and correlate with dehydration in seeds or vegetative tissues. In the present work, we analyze the protein composition of heat-stable Arabidopsis thaliana seed extracts after treatment with trichloroacetic acid (TCA). The composition of the proteins that precipitate and those that remain in solution in 3% TCA was analyzed by two different approaches: 1D SDS-PAGE coupled to LC-ESI-MSMS analysis and a gel-free protocol associated with LC-MALDI-MSMS. Our results indicate that treating total heat-soluble extracts with 3% TCA is an effective procedure to remove storage proteins by selective precipitation and this fractionation step provides a soluble fraction highly enriched in Lea-type proteins. The analysis and determination of protein identities in this acid-soluble fraction by MS technology is a suitable system for large-scale identification of Lea-proteins present in seeds.

Dielectric environment and/or random disorder effects on free, charged and localized excitonic states in monolayer WS2.

Excitonic effects play an important role on the optoelectronic behavior of atomically thin two-dimensional (2D) crystals of the WS2 transition metal dichalcogenide. In this paper, neutral and charged exciton behaviors in monolayer WS2 are handled within effective-mass approximation for which the critical parameters are ensured from our ab initio calculations. Firstly, we reveal an exciton series with a novel energy dependence on the orbital angular momentum. Considerable control of the dielectric environment on neutral and charged excitons binding energies is elucidated. We demonstrate that for accepted values of effective masses, the negative and positive trion binding energies should be identical. Secondly, localization of neutral exciton center of mass motion by random potential arising from monolayer defects is also studied. The results obtained are in agreement with available experimental work.

Indium selenide: an insight into electronic band structure and surface excitations.

We have investigated the electronic response of single crystals of indium selenide by means of angle-resolved photoemission spectroscopy, electron energy loss spectroscopy and density functional theory. The loss spectrum of indium selenide shows the direct free exciton at ~1.3 eV and several other peaks, which do not exhibit dispersion with the momentum. The joint analysis of the experimental band structure and the density of states indicates that spectral features in the loss function are strictly related to single-particle transitions. These excitations cannot be considered as fully coherent plasmons and they are damped even in the optical limit, i.e. for small momenta. The comparison of the calculated symmetry-projected density of states with electron energy loss spectra enables the assignment of the spectral features to transitions between specific electronic states. Furthermore, the effects of ambient gases on the band structure and on the loss function have been probed.

Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment.

Six hundred sixty-two consecutive patients with acetaminophen overdoses were evaluated. Those at risk on the basis of their acetaminophen blood levels, as plotted on the study nomogram, were treated with oral acetylcysteine. Statistically significant differences in severity of hepatic toxicity were observed between patients treated within 16 hours after ingestion and those treated between 16 and 24 hours after ingestion. No deaths occurred among patients treated within 24 hours of ingestion, except for one patient who was an alleged gunshot homicide. Seven percent of patients with plasma acetaminophen levels in the potentially toxic range and treated with acetylcysteine within ten hours of ingestion showed transient SGOT level elevations, whereas 29% of those treated between ten and 16 hours after ingestion and 62% of those treated between 16 and 24 hours after ingestion showed such transient toxicity. No consistent difference in hepatotoxicity could be demonstrated between those patients with a history of chronic alcohol use and those patients with no history of chronic alcohol use. Acute alcohol use resulted in less severe toxic reactions than in those patients without acute alcohol use.

Noninvasive assessment of pulmonary hypertension from right ventricular isovolumic contraction time.

In order to assess a noninvasive method of predicting pulmonary arterial pressure in adults, right ventricular systolic time intervals were determined with echocardiography simultaneously with pulmonary arterial end-diastolic pressure measurements. Right ventricular isovolumic contraction time was measured from echographic recordings of the tricuspid and pulmonary valves. Although this interval was found to increase as pulmonary arterial pressure increased, the method cannot be used to predict quantitatively the level of pulmonary arterial pressure in adults. However, an echocardiographically determined right ventricular contraction time of less than 25 ms suggests a normal pulmonary arterial pressure. In patients with pulmonary parenchymal diseases, echograms of the tricuspid and pulmonary valves are only rarely of such quality as to permit accurate delineation of the valvular events required for these measurements.

Pooling 12 nomifensine studies for efficacy generalizability.

Twelve parallel group, randomized, double-blind studies of nomifensine's safety and efficacy in the treatment of depressed patients were combined into three pools according to common protocols. This approach permitted evaluation of 1) efficacy results for studies with moderate-sized pools of patients, 2) the degree to which efficacy was generalizable to depressed patients in the general population, and 3) the conditions under which pooled active vs. active (imipramine vs. nomifensine) studies could be regarded as pivotal in support of efficacy. Results showed that nomifensine's superiority over placebo was generalizable to patients with a wide range of characteristics, including age 60 years or older. An appropriate statistical profile of more pronounced nomifensine responders would include patients with a duration of present episode less than 4 months who are acutely depressed, exhibit more severe symptoms, and have been previously hospitalized or treated with other psychotropic medications. A comprehensive assessment and power analysis of the pooled active vs. active studies provided strong evidence for comparability of nomifensine and imipramine.

Methylphenidate and memory: dissociated effects in hyperactive children.

Fourteen children with Attention Deficit Disorder with Hyperactivity (ADD + H) were administered the psychostimulant methylphenidate in a double-blind, placebo-controlled, crossover study. Subjects were evaluated on a well-validated measure of verbal memory and learning with an experimental design comprised of four conditions: placebo and active drug at three doses. Positive memory effects were found in the drug conditions. Significant dose-response relationships were found, indicating enhanced learning from placebo to low to medium to high dose. However, there was a differential drug effect on the memory task; methylphenidate selectively enhanced storage and retrieval mechanisms without affecting immediate acquisition.

Are American College of Rheumatology 50% response criteria superior to 20% criteria in distinguishing active aggressive treatment in rheumatoid arthritis clinical trials reported since 1997? A meta-analysis of discriminant capacities.

OBJECTIVE: To carry out a meta-analysis designed to compare the discriminant capacities of American College of Rheumatology 50% (ACR50) with 20% (ACR20) responses in clinical trials on rheumatoid arthritis reported after 1997 and to analyse whether ACR50 can be as informative as ACR20 in distinguishing active from control treatments in more recent trials. METHODS: Clinical trials on rheumatoid arthritis reported since 1997 were identified, which included aggressive combinations of disease-modifying antirheumatic drugs and glucocorticoids, as well as powerful new agents-leflunomide, etanercept, infliximab, anakinra, adalimumab, abatacept, tacrolimus and rituximab. A meta-analysis of ACR20 compared with ACR50 responses for 21 clinical trials was carried out on differences in proportions of responders for active and control treatments and corresponding odds ratios (ORs). RESULTS: In all but one clinical trial on rheumatoid arthritis published since 1997 with data available on ACR20 and ACR50, more than 50% of patients who were ACR20 responders among those randomised to active treatment were also ACR50 responders. This phenomenon was seen for control groups in 38% of trials, many of which included treatment with methotrexate. A meta-analysis of the clinical trials indicated a slight advantage to ACR50 for quantifying treatment comparisons, not significant for differences in proportions but significant for ORs. CONCLUSION: ACR20 and ACR50 seem to be similar in distinguishing active from control treatments in clinical trials on rheumatoid arthritis reported since 1997. As ACR50 represents a considerably stronger clinical response, ACR50 may be a preferred end point for contemporary clinical trials on rheumatoid arthritis.

Consistency in the diagnosis of the functional psychoses.

A review of the case books of 868 patients who had been admitted into a psychiatric hospital from January 1, 1970, to December 31, 1973, was carried out for consistency in the pattern of diagnosis by the same or different psychiatrists. Of these, 16.5% had a revision in diagnosis. The pertinent literature was reviewed. The possible factors that contribute to the observed inconsistency in diagnosis in this and other investigations are discussed. It is concluded that the problems as reflected in the significant change in diagnosis in this study are multifactorial. It is suggested that these problems may be related to the unknown etiology of the functional psychoses and the absence of identifiable specific lesions.

Evaluation of alternative statistical models for crossover studies to demonstrate caffeine adjuvancy in the treatment of tension headache.

This paper discusses alternative statistical models for the analysis of six crossover studies to determine whether better relief of tension headache occurs from treatment with an analgesic plus caffeine (C) than with the analgesic alone (A) or with placebo (P). Each patient in these crossover studies randomly received a pair of distinct medications in such a way as to treat the first two of four headaches with the initial medication in the pair and to treat the third and fourth headaches with the last medication in the pair. In order to have greater power for the C versus A comparison, three times as many patients were randomly assigned to the A:C and C:A sequence groups as to the A:P, C:P, P:A, and P:C sequence groups. An issue of statistical interest for these crossover studies is the extent to which the possibility of unequal carryover effects of the three medications influences the roles of alternative models for data analysis and the interpretation of results. When carryover effects for all three medications are equal, univariate analysis of variance for the difference scores between the average response for the first two headaches and the average response for the third and fourth headaches for each patient provides nearly the same power for pairwise treatment comparisons as more comprehensive multivariate methods for all four headaches. However, for comparisons concerning carryover effects and for treatment comparisons with adjustment for carryover effects, multivariate methods encompassing all four headaches jointly can provide greater power than univariate analysis for difference scores, particularly when there is low intraclass correlation for responses within the same patient. Another noteworthy role for multivariate methods in situations with potentially unequal carryover effects is their capacity to clarify whether multiple types of carryover effects occur across the second, third, and fourth headaches in the respective sequence groups. Multivariate models with alternative specifications of carryover effects are fit to the data from the six crossover studies to compare C, A, and P by weighted least squares. The role of potential variation among centers is addressed in these analyses by the use of stratified proportional means over centers, means of center means, and means ignoring centers. The primary focus of attention in the respective analyses is the evaluation of treatment comparisons with and without adjustment for potential differences among carryover effects of the treatments.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrotrichogenesis: further evidence of efficacy and safety on extended use.

These data represent a subset of data from the original 36-week study conducted by Maddin et al., which was in itself a preliminary study of a pulsed electrical stimulation device in male subjects alone. The extension phase of this study, which is summarized here, was undertaken to gather data on longer-term efficacy and safety and to study clinical effects in control subjects who were then switched to active treatment. Thirteen subjects had active treatment for 70 weeks, and 14 subjects were included in the crossover group, which had sham treatment for 36 weeks followed by active treatment for 30 additional weeks. On average, terminal hair counts increased from 82 to 276 in the active treatment group. Among those in the crossover group, a mild increase, from 124 to 160, was observed during the sham treatment period and a more notable increase, from 160 to 249, occurred during the subsequent active treatment period. The results presented here provide evidence of the efficacy and safety of this device during extended use; however, the generalizability of these findings is limited by the small subset of subjects for whom complete data are available.

Application of rank analysis of covariance methods to analysis of multiple anatomical regions with treatment for seborrheic dermatitis.

This paper presents the advantages of rank analysis of covariance in contrast to the Mantel-Haenszel procedure in the presence of a covariate. In this paper, data from a clinical trial with an indication for seborrheic dermatitis, which afflicts multiple anatomical regions, is presented. This paper presents analysis performed using both the Mantel-Haenszel procedure and rank analysis of covariance for separate anatomical regions, as well as for the combined anatomical regions. The analysis for the combined anatomical regions involves weighted sums over different strata.

The withdrawal of benztropine mesylate in chronic schizophrenic patients.

In this double-blind, four-week study, 28 chronic schizophrenic patients receiving neuroleptic medication plus the antiparkinsonian drug, benztropine mesylate, were either switched to placebo or maintained on benztropine. Patients withdrawn from benztropine reliably increased their overall scores on the Wechsler Memory Scale in comparison with the drug group. Sub-test scores suggest that deficits in attention and concentration were induced by treatment with benztropine. Psychotic decompensation appeared to develop simultaneously with extrapyramidal symptoms (EPS) in some patients, but only 14.2 per cent of the placebo group experienced extrapyramidal symptoms severe enough to require resumption of benztropine therapy. It is suggested that antiparkinsonian agents should be prescribed only if and when EPS occur.