Regulation of constitutive and induced NF-kappaB activation in malignant melanoma cells by capsaicin modulates interleukin-8 production and cell proliferation.

In the present study, we demonstrate that upregulation of interleukin-1beta(IL-1beta)-mediated and tumor necrosis factor-alpha (TNF-alpha)-mediated IL-8 expression in human malignant melanoma cells is modulated by the activation of nuclear factor-kappaB (NF-kappaB). Addition of capsaicin (8-methyl-N-vanillyl-6-nonenamide), a known inhibitor of NF-kappaB, resulted in the inhibition of constitutive as well as IL-1beta-induced and TNF-alpha-induced IL-8 expression in melanoma cells. The inhibition of IL-8 expression was dependent on the concentration of capsaicin and duration of treatment. Further, electrophoretic mobility shift assay (EMSA) of nuclear extracts from melanoma cells showed a constitutive activation of NF-kappaB and activated protein 1 (AP-1), which was upregulated following treatment with IL-1beta. Treatment of melanoma cells with capsaicin inhibited activation of constitutive and IL-1beta-induced NF-kappaB, but not AP-1, leading to inhibition of IL-8 expression. Further, downregulation of IL-8 expression in capsaicin-treated melanoma cells resulted in inhibition of in vitro cell proliferation. These results demonstrate that constitutive and induced NF-kappaB activation regulates IL-8 expression in melanoma cells. Downregulation of constitutive and induced NF-kappaB activation in malignant melanoma cells leads to inhibition of IL-8 production and in vitro cell proliferation.     

Identification of coagulase negative staphylococcal species from bovine mastitis in India

Background:Staphylococcal mastitis is a major cause of concern to the dairy industry in India and several countries worldwide. Though Staphylococcus aureus is the major cause, coagulase negative staphylococcal species (CoNS) are being increasingly reported in recent years. Aims:To investigate the incidence of coagulase negative staphylococcal species in bovine mastitis. Methods:Isolation of staphylococci was carried out from 237 milk samples of cows and She buffaloes with clinical and subclinical mastitis from different regions of Andhra Pradesh and Karnataka. CoNS isolates were identified by tube coagulase test using fresh rabbit plasma and coagulase gene PCR. We employed the biochemical test scheme published elsewhere previously for identification of the CoNS isolates up to species and subspecies levels. Seven representative isolates were identified by 16S rDNA sequencing to check the accuracy of biochemical test based identification. Results:The CoNS constitute the majority of the staphylococcal isolates from mastitis (80/125, 64%) in this region. Using biochemical test scheme, the CoNS isolates from bovine mastitis were identified as S. cohnii sub sp. cohnii, S. simulans, S. capitis sub sp. capitis, S. cohnii sub sp. xylosus, and S. lugdunensis. The CoNS species S. schleiferi, S. haemolyticus, S. sciuri, S. xylosus, S. chromogenes, and Macrococcus epidermidis were identified by 16S rDNA sequencing. Conclusion:The 16S rDNA sequencing is the appropriate method for the identification of CoNS species. This study highlighted coagulase negative staphylococcal species as possible etiological agents of mastitis.Key Words: 16S rDNA sequencing, Biochemical test scheme, Coagulase negative staphylococci, Species identification     

Interventions to Reduce Risk for Pathogen Spillover and Early Disease Spread to Prevent Outbreaks,Epidemics, and Pandemics

The pathogens that cause most emerging infectious diseases in humans originate in animals, particularly wildlife, and then spill over into humans. The accelerating frequency with which humans and domestic animals encounter wildlife because of activities such as land-use change, animal husbandry, and markets and trade in live wildlife has created growing opportunities for pathogen spillover. The risk of pathogen spillover and early disease spread among domestic animals and humans, however, can be reduced by stopping the clearing and degradation of tropical and subtropical forests, improving health and economic security of communities living in emerging infectious disease hotspots, enhancing biosecurity in animal husbandry, shutting down or strictly regulating wildlife markets and trade, and expanding pathogen surveillance. We summarize expert opinions on how to implement these goals to prevent outbreaks, epidemics, and pandemics.     

Granulomatous Variant of Giant Centrifugal Miliaria Profunda

Abstract: Two infants presented with multiple asymptomatic papules and geographic and annular plaques over the extensor aspect of the upper and lower extremities and trunk. Skin biopsy of both lesions showed plugged and hyperplastic dilated acrosryingia and deep dermal ducts, along with granulomatous inflammatory reaction. These lesions showed self‐healing with complete resolution. A previous report described similar clinical and histopathologic features and labeled it giant centrifugal miliaria profunda. Because of the large granulomatous plaques and deep infiltrate, we propose that it was a granulomatous variant of giant centrifugal miliaria profunda. We report these cases for their rarity and self‐healing nature.     

Acute Disseminated Encephalomyelitis following Seasonal Influenza Vaccination in an Elderly Patient

Although such occurrences are rare, it should be recognized that certain vaccines might trigger serious neurological immune phenomena such as Guillain-Barre syndrome, seizures, cranial neuropathy, and acute disseminated encephalomyelitis (ADEM). Here we report on an elderly woman with ADEM following seasonal influenza vaccination who recovered after plasma exchange.     

KAP Studies Among Indian Antenatal Women: Can We Reduce the Incidence of Anemia?

Aim

To study the knowledge, attitude, and practices of antenatal women regarding nutrition and drug compliance in a maternal and child health center in Navi Mumbai.

Material and Methods

This study was carried out on 250 pregnant females visiting a maternal and child health center over a period of 4 months from November 2012 to February 2013. Women attending the antenatal OPD were asked to fill a questionnaire regarding anemia so as to test their knowledge, attitudes, and practices pertaining to anemia and role of their diet.

Observation

The observations were analyzed. This study reflects the ignorance and lack of education among the majority of child-bearing women of low socioeconomic class.

Conclusion

Educating antenatal women about the importance of diet and implementing this into practice will help in the prevention of anemia. It is also seen that drug compliance for iron and folic acid (free supply) has significantly improved, not only because of the cost factor but also due to the reinforcement of knowledge by the staff so as to achieve the minimum WHO target hemoglobin of 10.5 g% in all mothers.

Electronic supplementary material

The online version of this article (doi:10.1007/s13224-014-0618-0) contains supplementary material, which is available to authorized users.     

Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation

Activation of CD4⁺ T cells results in rapid proliferation and differentiation into effector and regulatory subsets. CD4⁺ effector T cell (Teff) (Th1 and Th17) and Treg subsets are metabolically distinct, yet the specific metabolic differences that modify T cell populations are uncertain. Here, we evaluated CD4⁺ T cell populations in murine models and determined that inflammatory Teffs maintain high expression of glycolytic genes and rely on high glycolytic rates, while Tregs are oxidative and require mitochondrial electron transport to proliferate, differentiate, and survive. Metabolic profiling revealed that pyruvate dehydrogenase (PDH) is a key bifurcation point between T cell glycolytic and oxidative metabolism. PDH function is inhibited by PDH kinases (PDHKs). PDHK1 was expressed in Th17 cells, but not Th1 cells, and at low levels in Tregs, and inhibition or knockdown of PDHK1 selectively suppressed Th17 cells and increased Tregs. This alteration in the CD4⁺ T cell populations was mediated in part through ROS, as N-acetyl cysteine (NAC) treatment restored Th17 cell generation. Moreover, inhibition of PDHK1 modulated immunity and protected animals against experimental autoimmune encephalomyelitis, decreasing Th17 cells and increasing Tregs. Together, these data show that CD4⁺ subsets utilize and require distinct metabolic programs that can be targeted to control specific T cell populations in autoimmune and inflammatory diseases.