Metoclopramide-induced central nervous system depression in the chicken

Background

Metoclopramide is a dopamine D2-receptor antagonist used as an antiemetic and gastroprokinetic agent in man and animals. The drug causes sedation as a side effect in man. Such a sedative action of metoclopramide has not been documented in the chicken as the drug is not used clinically in this species. The present study examines the central nervous system depressant effects of metoclopramide in 7–14 days old broiler chicks.

Results

Injection of metoclopramide at 50, 100 and 200 mg/kg, subcutaneously (s.c.) induced sedation in the chicks in a dose dependent manner. The chicks manifested, within 3.6–19 minutes of metoclopramide injection, signs of sedation characterized by drooping of the head and wings, closed eyelids, reduced motility and decreased distress calls. The duration of sedation ranged between 37.2 to 163.4 minutes. Metoclopramide at 100 and 200 mg/kg induced, within 12.2 and 6.2 minutes, sleep (loss of righting reflex) for 43.8 and 158.6 minutes, respectively. The median effective doses of metoclopramide for induction of sedation and sleep in the chicks were 11 and 53 mg/kg, s.c., respectively. Lower doses of metoclopramide (5 and 10 mg/kg, s.c.) significantly decreased the open-field activity of the chicks and increased the durations of their tonic immobility. All treated-chicks recovered from the central nervous system depressant effect of metoclopramide without any observable adverse effects.

Conclusion

The data suggest that metoclopramide induces central nervous system depression in chicks, and the drug could have potential clinical applications as a sedative-hypnotic agent in avian species not intended for human consumptions.     

ULIXES, unravelling and exploiting Mediterranean Sea microbial diversity and ecology for xenobiotics’ and pollutants’ clean up

The civilizations in the Mediterranean Sea have deeply changed the local environment, especially with the extraction of subsurface oil and gas, their refinery and transportation. Major environmental impacts are affecting all the sides of the basin with actual and potential natural and socio-economic problems. Events like the recent BP??s oil disaster in the Gulf of Mexico would have a tremendous impact on a close basin like the Mediterranean Sea. The recently EU-funded project ULIXES (http://www.ulixes.unimi.it/) aims to unravel, categorize, catalogue, exploit and manage the microbial diversity available in the Mediterranean Sea for addressing bioremediation of polluted marine sites. The rationale of the project is based on the multiple diverse environmental niches of the Mediterranean Sea and the huge range of microorganisms inhabiting therein. Microbial consortia and their ecology, their components or products are used for designing novel pollutant- and site-tailored bioremediation approaches. ULIXES exploits microbial resource mining by the isolation of novel microorganisms as well as by novel advanced ??meta-omics?? technologies for solving pollution of three major high priority pollutant classes, petroleum hydrocarbons, chlorinated compounds and heavy metals. A network of twelve European and Southern Mediterranean partners is exploring the microbial diversity and ecology associated to a large set of polluted environmental matrices including seashore sands, lagoons, harbors and deep-sea sediments, oil tanker shipwreck sites, as well as coastal and deep sea natural sites where hydrocarbon seepages occur. The mined collections are exploited for developing novel bioremediation processes to be tested in ex situ and in situ field bioremediation trials.     

Intratumoral Delivery of Paclitaxel in Solid Tumor from Biodegradable Hyaluronan Nanoparticle Formulations

In the current study, novel paclitaxel-loaded cross-linked hyaluronan nanoparticles were engineered for the local delivery of paclitaxel as a prototype drug for cancer therapy. The nanoparticles were prepared using a desolvation method with polymer cross-linking. In vitro cytotoxicity studies demonstrated that less than 75% of the MDA-MB-231 and ZR-75-1 breast cancer cells were viable after 2-day exposure to paclitaxel-loaded hyaluronan nanoparticles or free paclitaxel, regardless of the dose. These results suggest that hyaluronan nanoparticles maintain the pharmacological activity of paclitaxel and efficiently deliver it to the cells. Furthermore, in vivo administration of the drug-loaded nanoparticles via direct intratumoral injection to 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor in female rats was studied. The paclitaxel-loaded nanoparticles treated group showed effective inhibition of tumor growth in all treated rats. Interestingly, there was one case of complete remission of tumor nodule and two cases of persistent reduction of tumor size that was observed on subsequent days. In the case of free paclitaxel-treated group, the mean tumor volume increased almost linearly (R ² = 0.93) with time to a size that was 4.9-fold larger than the baseline volume at 57 days post-drug administration. Intratumoral administration of paclitaxel-loaded hyaluronan nanoparticles could be a promising treatment modality for solid mammary tumors.     

Patterns of testicular cytology in men with primary infertility: any change since the Gulf War?

OBJECTIVE: To evaluate the patterns of testicular cytology in men with primary infertility, to compare the morphologic patterns between the periods 1990-1995, immediately after Gulf War II, and 1997-2001 and to determine whether there is a correlation between hormonal profile, testicular volume and morphologic pattern. STUDY DESIGN: Retrospective study of men with primary infertility. History, complete physical examination, hormonal assay and testicular ultrasound were evaluated. A total of 545 patients had samples for testicular cytology obtained from both testes. The patient's consent was obtained in all cases. Smears were interpreted under light microscopy after treatment with Diff-Quik. A total of 104 healthy, fertile subjects were used for comparison of the hormonal profile and testicular volume. RESULTS: The mean (+/- SD) age was 28.66 +/- 4.36 years and duration of marriage 4.4 +/- 4.36 years. There were 11.2% patients with normal cytology, 55.8% with hypospermatogenesis, 28.4% with testicular atrophy, 2.9% with Sertoli cells only and 1.7% with maturation arrest. A significant increase in hypospermatogenesis and decrease in the Sertoli cell-only pattern were noted in 1997-2001 when compared with 1990-1995. The mean left testicular volume was 10.53 +/- 5.51 mL3 in the infertile group vs. 15.2 +/- 4.97 in the fertile group (p < 0.003); right testicular volume was 10.84 +/- 4.77 vs. 15.15 +/- 5.31 (p < 0.003). The hormonal profile revealed higher luteinizing hormone and follicle-stimulating hormone levels in the infertile group vs. control group (8.53 +/- 9.03 and 16.44 +/- 19.243 vs. 6.98 +/- 4.53 and 7.37 +/- 6.63, respectively [p < 0.001]). Free testosterone was higher in the fertile group (39.69 +/- 12.76 vs. 20.28 +/- 8.5 [p < 0.000]). CONCLUSION: The majority of infertile males in our cohort had hypospermatogenesis; testicular atrophy was the next most common disorder. There was no major change in overall absolute numbers since the Gulf War. Testicular cytology by fine needle aspiration is a safe and well-tolerated complementary investigation for unexplained male infertility.     

Use of RAPD-PCR fingerprinting to detect genetic diversity of soil Streptomyces isolates

Random amplified polymorphic DNA (RAPD) was used for identification and assessment of genetic diversity between isolates of Streptomyces from soil. Genomic DNA from 18 Streptomyces isolates and 2 reference strains were amplified using four different 10-mer primers. Different DNA fingerprinting patterns were obtained for all the isolates. Electrophoretic and cluster analysis of the amplification products revealed incidence of polymorphism among the isolates and none of them was identical to the reference strains although there were some common amplification bands. Two highly divergent groups were determined among the isolates. The results indicate that RAPD is an efficient method for discriminating and studying genetic diversity of Streptomyces isolates.     

<Emphasis Type="Italic">Arbutus andrachne</Emphasis> L. Reverses Sleep Deprivation-Induced Memory Impairments in Rats

Sleep deprivation (SD) is associated with cognitive deficits. It was found to affect the hippocampus region of the brain by impairing memory formation. This impairment is suggested to be caused by elevation in oxidative stress in the body, including the brain during SD. It was hypothesized that the methanolic extract of the fruits of Arbutus andrachne L. (Ericaceae) will prevent chronic SD-induced impairment of hippocampal memory via its antioxidative properties. The methanolic extract of the fruits of A. andrachne was evaluated for its beneficial properties to reverse SD-induced cognitive impairment in rats. Animals were sleep deprived for 8 weeks using a multiple platform model. The extract was administered i.p. at three doses (50, 200, and 500 mg/kg). Behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM). In addition, the hippocampus was dissected to analyze the following oxidative stress markers: glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG, glutathione peroxidase (GPx), and catalase. Chronic SD impaired short- and long-term memories (P < 0.05). Treatment of animals with A. andrachne fruit extract at all doses prevented long-term memory impairment induced by SD while such treatment prevented short-term memory impairment only at 200 and 500 mg/kg dose levels. Moreover, A. andrachne fruit extract normalized the reduction in the hippocampus GSH/GSSG ratio and activity of GPx, and catalase (P < 0.05) induced by chronic sleep deprivation. Chronic sleep deprivation impaired both short- and long-term memory formation, while methanolic extract of A. andrachne fruits reversed this impairment, probably through normalizing oxidative stress in the hippocampus.     

Assessing horizontal transfer of nifHDK genes in eubacteria: nucleotide sequence of nifK from Frankia strain HFPCcI3

The structural genes for nitrogenase, nifK, nifD, and nifH, are crucial for nitrogen fixation. Previous phylogenetic analysis of the amino acid sequence of nifH suggested that this gene had been horizontally transferred from a proteobacterium to the gram-positive/cyanobacterial clade, although the confounding effects of paralogous comparisons made interpretation of the data difficult. An additional test of nif gene horizontal transfer using nifD was made, but the NifD phylogeny lacked resolution. Here nif gene phylogeny is addressed with a phylogenetic analysis of a third and longer nif gene, nifK. As part of the study, the nifK gene of the key taxon Frankia was sequenced. Parsimony and some distance analyses of the nifK amino acid sequences provide support for vertical descent of nifK, but other distance trees provide support for the lateral transfer of the gene. Bootstrap support was found for both hypotheses in all trees; the nifK data do not definitively favor one or the other hypothesis. A parsimony analysis of NifH provides support for horizontal transfer in accord with previous reports, although bootstrap analysis also shows some support for vertical descent of the orthologous nifH genes. A wider sampling of taxa and more sophisticated methods of phylogenetic inference are needed to understand the evolution of nif genes. The nif genes may also be powerful phylogenetic tools. If nifK evolved by vertical descent, it provides strong evidence that the cyanobacteria and proteobacteria are sister groups to the exclusion of the firmicutes, whereas 16S rRNA sequences are unable to resolve the relationships of these three major eubacterial lineages.