Clinical response to antibiotics among children with bloody diarrhea

WHO recommends ciprofloxacin as the drug of choice for bloody diarrhea. We retrospectively analyzed antibiotic response in 100 children with bloody diarrhea admitted between 2006–2010. Cotrimoxazole (n=55) had higher chance of attaining improved appetite and normal activity in 48h, hospitalization of <3d, blood disappearance in ≤5d and not requiring a second antibiotic compared to others (n=45). Older antimicrobials should be tried in all possible situations.     

Bright blue emitting CuSe/ZnS/silica core/shell/shell quantum dots and their biocompatibility

In the in vivo scenario, the nanomaterials have to stay for a prolonged period in fluids like blood and therefore a detailed understanding of their interaction with blood elements is mandatory. We report the synthesis and characterization of highly blue emitting smaller size, 3.6 nm CuSe quantum dots (QDs) and its core/shell structure CuSe/ZnS. We modified QDs with a silica shell, which is the most accepted approach to lessen the toxic liabilities, and the blood compatibility of resultant CuSe/ZnS/Silica QDs were evaluated. MTT assay and cellular uptake using HepG2 and C 6 glioma cancer cells were studied to show their potential as drug targeting vehicles. The documented observation to date about the silica on cells is its ability to cause apoptosis by the production of reactive oxygen species. However, its impact on the blood cells has never been addressed or studied in detail. Our data indicate that concentrations of ≤50 μg/mL CuSe/ZnS/Silica QDs are blood compatible. The concentration dependant blood compatibility of silica modified QDs, point out the need for rethinking of using silica coatings over nanomaterials for diverse applications like drug targeting and cellular labeling.     

Alpha-melanocyte-stimulating hormone down-regulates CXC receptors through activation of neutrophil elastase

Considering the role of interleukin-8 (IL-8) in a large number of acute and chronic inflammatory diseases, the regulation of IL-8-mediated biological responses is important. Alpha-melanocyte-stimulating hormone (alpha-MSH), a tridecapeptide, inhibits most forms of inflammation by an unknown mechanism. In the present study, we have found that alpha-MSH interacts predominantly with melanocortin-1 receptors and inhibits several IL-8-induced biological responses in macrophages and neutrophils. It down-regulated receptors for IL-8 but not for TNF, IL-4, IL-13 or TNF-related apoptosis-inducing ligand (TRAIL) in neutrophils. It down-regulated CXCR type 1 and 2 but not mRNA levels. alpha-MSH did not inhibit IL-8 binding in purified cell membrane or affinity-purified CXCR. IL-8 or anti-CXCR Ab protected against alpha-MSH-mediated inhibition of IL-8 binding. The level of neutrophil elastase, a specific serine protease, but not cathepsin G or proteinase 3 increased in alpha-MSH-treated cells, and restoration of CXCR by specific neutrophil elastase or serine protease inhibitors indicates the involvement of elastase in alpha-MSH-induced down-regulation of CXCR. These studies suggest that alpha-MSH inhibits IL-8-mediated biological responses by down-regulating CXCR through induction of serine protease and that alpha-MSH acts as a potent immunomodulator in neutrophil-driven inflammatory distress.     

Subchronic exposure to mitragynine,the principal alkaloid of Mitragyna speciosa, in rats

Ethnopharmacological relevance

Mitragyna speciosa is a popular medicinal plant in Southeast Asia which is commonly used for its morphine-like effects. Although the analgesic properties of Mitragyna speciosa and its ability to ameliorate withdrawal signs after abrupt cessation of opioid abuse are well known, information about the long-term safety of the plant's active compounds is lacking. In this work, we evaluated the effects of sub-chronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa leaves in rats. Materials and methods: Male and female Sprague-Dawley rats received three doses of mitragynine (1, 10, 100 mg/kg, p.o) for 28 days respectively. Food intake and relative body weight were measured during the experiment. After completion of drug treatment biochemical, hematological, and histological analyses were performed.

Results

No mortality was observed in any of the treatment groups. The groups of rats treated with the lower and intermediate doses showed no toxic effects during the study. However, the relative body weight of the group of female rats treated with the 100 mg/kg dose was decreased significantly. Food intake also tended to decrease in the same group. Only relative liver weight increased after treatment with the high dose of mitragynine (100 mg/ kg) in both the male and female treatment groups of rats. Biochemical and hematological parameters were also altered especially in high dose treatment group which corresponds to the histopathological changes.

Conclusions

The study demonstrated that mitragynine is relatively safe at lower sub-chronic doses (1–10 mg/kg) but exhibited toxicity at a highest dose (sub-chronic 28 days: 100 mg/kg). This was confirmed by liver, kidney, and brain histopathological changes, as well as hematological and biochemical changes.     

Self-similar Rayleigh–Taylor mixing with accelerations varying in time and space

As a ubiquitous paradigm of instabilities and mixing that occur in instances as diverse as supernovae, plasma fusion, oil recovery, and nanofabrication, the Rayleigh–Taylor (RT) problem is rightly regarded as important. The acceleration of the fluid medium in these instances often depends on time and space, whereas most past studies assume it to be constant or impulsive. Here, we analyze the symmetries of RT mixing for variable accelerations and obtain the scaling of correlations and spectra for classes of self-similar dynamics. RT mixing is shown to retain the memory of deterministic conditions for all accelerations, with the dynamics ranging from superballistic to subdiffusive. These results contribute to our understanding and control of the RT phenomena and reveal specific conditions under which Kolmogorov turbulence might be realized in RT mixing.

Turbulence is an unfinished problem of classical physics. Its theoretical richness attracts physicists and mathematicians alike, while its practical importance demands the attention of engineers and practitioners. Isotropy, homogeneity, and localness of scale-to-scale interactions are some of the fundamental paradigms that have advanced our understanding of turbulent dynamics. However, realistic processes often depart from these ideal paradigms. An important class of such processes is linked to the Rayleigh–Taylor (RT) mixing encountered in a large variety of configurations (1, 2).RT instability occurs when the fluid interface is perturbed near the equilibrium state and develops under an accelerating velocity field. When the acceleration is constant, the instability is referred to as the classical RT instability, and the impulsive (e.g., shock-driven) case is known as the Richtmyer–Meshkov (RM) instability (3, 4). In general, the flow transitions from an initial stage of quick perturbation growth to a nonlinear stage, in which the growth rate slows and the interface is transformed to a combination of the large-scale coherent structure and shear-driven small scales. The final stage of this instability is an intense interfacial mixing, whose dynamics is believed to be self-similar. For an appreciation of the problem in a rich variety of contexts, see refs. 5–22.This work adopts continuum fluid equations and advances the significant success achieved via the group-theory approach analyzing symmetries and invariant properties of RT dynamics (19, 22, 23). We explore the special classes of self-similar dynamics of RT mixing driven by accelerations that obey power laws in time and in space, which have not been discussed in earlier work (22–25). Our results explain existing experiments, broaden the horizons of studies of RT-relevant processes, and outline conditions under which Kolmogorov turbulence may manifest in RT/RM mixing.     

Evaluation of hepatoprotective effect of methanolic extract of Clitoria ternatea (Linn.) flower against acetaminophen-induced liver damage

Objective

To evaluate the hepatoprotective and antioxidant activity of Clitoria ternatea (C. ternatea) flower extract against acetaminophen-induced liver toxicity.

Methods

The antioxidant property of C. ternatea flower extract was investigated by employing established in vitro antioxidant assay. The C. ternatea flower extract was studied in this work for its hepatoprotective effect against acetaminophen-induced liver toxicity in mice. Activity was measured by monitoring the levels of aspartate aminotransferase, alanine aminotransferase, billirubin and glutathione with histopathological analysis.

Results

The amount of total phenolics and flavonoids were estimated to be 105.40±2.47 mg/g gallic acid equivalent and 72.21±0.05 mg/g catechin equivalent respectively. The antioxidant activity of C. ternatea flower extract was 68.9% at a concentration of 1 mg/mL and was also concentration dependant, with an IC₅₀ value of 327.00 µg/mL. The results of acetaminophen-induced liver toxicity experiment showed that mice treated with the extract (200 mg/kg) showed a significant decrease in alanine aminotransferase, aspartate aminotransferase, and bilirubin levels, which were all elevated in the paracetamol group (P<0.05). Meanwhile, the level of glutathione was found to be restored in extract treated animals compared to the groups treated with acetaminophen alone (P<0.05). Therapy of extract also showed its protective effect on histopathological alterations and supported the biochemical finding.

Conclusion

The present work confirmed the hepatoprotective effect of C. ternatea flower against model hepatotoxicant acetaminophen.