Formulation and <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Lipid-Based Terbutaline Sulphate Bi-layer Tablets for Once-Daily Administration

The objective of this study was to prepare and evaluate terbutaline sulphate (TBS) bi-layer tablets for once-daily administration. The bi-layer tablets consisted of an immediate-release layer and a sustained-release layer containing 5 and 10 mg TBS, respectively. The sustained-release layer was developed by using Compritol®888 ATO, Precirol® ATO 5, stearic acid, and tristearin, separately, as slowly eroding lipid matrices. A full 4?×?2² factorial design was employed for optimization of the sustained-release layer and to explore the effect of lipid type (X ₁), drug–lipid ratio (X ₂), and filler type (X ₃) on the percentage drug released at 8, 12, and 24 h (Y ₁, Y ₂, and Y ₃) as dependent variables. Sixteen TBS sustained-release matrices (F1–F16) were prepared by melt solid dispersion method. None of the prepared matrices achieved the targeted release profile. However, F2 that showed a relatively promising drug release was subjected to trial and error optimization for the filler composition to develop two optimized matrices (F17 and F18). F18 which consisted of drug–Compritol®888 ATO at ratio (1:6 w/w) and Avicel PH 101/dibasic calcium phosphate mixture of 2:1 (w/w) was selected as sustained-release layer. TBS bi-layer tablets were evaluated for their physical properties, in vitro drug release, effect of storage on drug content, and in vivo performance in rabbits. The bi-layer tablets showed acceptable physical properties and release characteristics. In vivo absorption in rabbits revealed initial high TBS plasma levels followed by sustained levels over 24 h compared to immediate-release tablets.     

Platelet-rich plasma ameliorates neurotoxicity induced by silver nanoparticles in male rats via modulation of apoptosis,inflammation, and oxidative stress

The widespread use of silver in various forms raises concerns about its potential adverse effects. Silver nanoparticles (AgNPs) can enter the brain and subsequently induce neurotoxicity. As a source of diverse growth factors and for its cytoprotective properties, platelet-rich plasma (PRP) has received considerable attention in regenerative medicine. Our aim was to estimate the toxic effects of AgNPs on the rat brain and assess the possible protective effects of PRP against AgNPs induced neurotoxicity. A total of 40 adult male rats were divided into four groups (n = 10), namely the control, AgNPs, AgNPs+PRP, and auto-recovery groups. AgNPs were given intraperitoneally (i.p.) at a 10 mg/kg dose.bw daily for 28 days. PRP was given (a day after AgNPs treatment) i.p. at a dose of 0.5 mL/kg.bw twice weekly for 3 weeks. Rats in the auto-recovery group were left without treatment for 3 weeks after AgNP toxicity. Serum and brain tissue samples were collected for assessment of proinflammatory cytokines, oxidative stress markers, as well as the expression levels of apoptotic markers. Brain histopathological and immunohistochemistry examinations were done. AgNPs significantly increased oxidative stress markers and proinflammatory cytokines, decreased antioxidant defense markers, and induced apoptosis and histopathological brain injuries. However, PRP treatment restored brain oxidant/antioxidant balance, attenuated the inflammatory state, prevented apoptosis, and improved the brain histopathological lesions induced by AgNPs, with no significant improvements shown by auto-recovery group. Our data provided a novel protective effect for PRP against AgNPs-induced neurotoxicity due to its antioxidant, anti-inflammatory, and antiapoptotic effects.     

Cytogenetic effects of sildenafil citrate (Viagra) on SWR/J mouse bone marrow cells

The present study was conducted to investigate the cytogenetic effects of sildenafil citrate in SWR/J mouse bone marrow cells. Thirty-six males and 36 females were used and divided into four groups. Each group contained 18 animals (9 males and 9 females), weighing 30–35 g. These animals were orally administered with a single dose of 13, 26 or 40 mg/kg sildenafil citrate solution. A control group received normal saline in an identical condition. The animals were sacrificed at 12, 24 or 48 h, after the treatment. Chromosome aberrations were investigated in 50 metaphases per animal.No significant differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between treated male and female mice at any doses or at any time intervals used, therefore, data from the two sexes were pooled when analyzed statistically.No significant (p < 0.05) differences in the percentages of mitotic indices or in the frequencies of chromosome aberrations were observed between sildenafil citrate-treated groups and the control group at any doses or at any time intervals used. However, the percentages of centromeric adhesions increased significantly (p < 0.01) in treated groups as compared with the control group at all doses and at all time intervals used.In conclusion, the results of the present study suggest that sildenafil citrate does not have cytogenetic effects on mouse bone marrow cells, but the centromeric adhesions induced by this drug need further studies to confirm them and to investigate the possible mechanism(s) responsible for such effect.     

Effect of the new potent LHRH antagonist antide

The ability of the new LHRH antagonist antide to induce a long-term chemical castration in adult male rats and cynomolgus monkeys was investigated. The animals were treated subcutaneously with different doses either once or on 5 consecutive days. The effects on serum concentration of LH (only rat) and testosterone and on the weights of the testes, prostates and seminal vesicles were investigated after different periods of time. Histological evaluation of testes, pituitary and hypothalamus was also performed. In the rat a clear dose-dependent inhibitory effect on the above mentioned parameters was observed whereby long-lasting castration-like effects were achieved at concentrations between 6 (8 weeks) and 15 mg/kg (> 8 weeks). In the cynomolgus monkey a prolonged inhibitory effect was induced only at 15 mg/kg and the duration was only 2–3 weeks. Histologically, no signs indicative of irreversible effects were observed in either species. In conclusion: although species differences became evident in terms of the duration of a long-lasting inhibutory effect on the male reproductive system, antide exhibited such an effect in the rat and the monkey and was able to induce a chemical castration in both species. In addition, using the rat Dunning R 3327 prostatic carcinoma model, 10 mg/kg antide given subcutaneously every 6 weeks for a total period of 26 weeks, had an inhibitory effect on tumor growth identical to that of castration emphasizing the suitability of this compound for treatment of prostatic cancer.     

Correction: Genotypic detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis strains by DNA sequencing: a randomized trial

Correction to Genotypic detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis strains by DNA sequencing: a randomized trial Amina Abdelaal, Hassan Abd El-Ghaffar, Mohammad Hosam Eldeen Zaghloul, Noha El mashad, Ehab Badran, Amal Fathy Annals of Clinical Microbiology and Antimicrobials 2009, 8:4 (30 January 2009)     

Initial characterization of an autoclaved Toxoplasma vaccine in mice

Toxoplasmosis is a zoonotic protozoal disease that has a major significance from the perspectives of public health and veterinary medicine. Therefore, an obvious long-term goal of many scientists would be the development of an effective vaccine. In this study, autoclaved vaccine was evaluated for its ability to protect mice against Toxoplasma gondii RH challenge as an acute infection model. Results showed that autoclaved Toxoplasma vaccine (ATV) when combined with BCG as an adjuvant was effective in triggering cell mediated immunity as shown by a significant increase in the percentage of splenic CD8+ T-lymphocytes. Following challenge, death of mice vaccinated with ATV was delayed for nine days. There was a significant decrease in parasite density in different organs, and a marked reduction of pathological changes in the liver suggesting that significant immune responses were mounted following vaccination. Future studies are warranted to test the vaccine against challenge with brain cysts as a chronic infection model and to evaluate it with other recent immunization strategies that can further enhance its immunogenicity.     

Proteomic profiling of aging in the mouse heart: Altered expression of mitochondrial proteins

Using two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry, we have used a systems biology approach to study the molecular basis of aging of the mouse heart. We have identified 8 protein spots whose expression is up-regulated due to aging and 36 protein spots whose expression is down-regulated due to aging (p0.05 as judged by Wilcoxon Rank Sum test). Among the up-regulated proteins, we have characterized 5 protein spots and 2 of them, containing 3 different enzymes, are mitochondrial proteins. Among the down-regulated proteins, we have characterized 27 protein spots and 16 of them are mitochondrial proteins. Mitochondrial damage is believed to be a key factor in the aging process. Our current study provides molecular evidence at the level of the proteome for the alteration of structural and functional parameters of the mitochondria that contribute to impaired activity of the mouse heart due to aging.     

Impact of the age of Biomphalaria alexandrina snails on Schistosoma mansoni transmission: modulation of the genetic outcome and the internal defence system of the snail

Of the approximately 34 identified Biomphalariaspecies,Biomphalaria alexandrina represents theintermediate host of Schistosoma mansoni in Egypt. Usingparasitological and SOD1 enzyme assay, this study aimed to elucidate the impact ofthe age of B. alexandrina snails on their genetic variability andinternal defence against S. mansoni infection. Susceptible andresistant snails were reared individually for self-reproduction; four subgroups oftheir progeny were used in experiment. The young susceptible subgroup showed thehighest infection rate, the shortest pre-patent period, the highest total cercarialproduction, the highest mortality rate and the lowest SOD1 activity. Among the youngand adult susceptible subgroups, 8% and 26% were found to be resistant, indicatingthe inheritance of resistance alleles from parents. The adult resistant subgroup,however, contained only resistant snails and showed the highest enzyme activity. Thecomplex interaction between snail age, genetic background and internal defenceresulted in great variability in compatibility patterns, with the highest significantdifference between young susceptible and adult resistant snails. The resultsdemonstrate that resistance alleles function to a greater degree in adults, withhigher SOD1 activity and provide potential implications for Biomphalariacontrol. The identification of the most susceptible snail age enablesdetermination of the best timing for applying molluscicides. Moreover, adultresistant snails could be beneficial in biological snail control.