Development and Evaluation of a Novel Modified-Release Pellet-Based Tablet System for the Delivery of Loratadine and Pseudoephedrine Hydrochloride as Model Drugs

Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion–spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.     

Characterization and Comparison of Clavibacter michiganensis subsp. nebraskensis Strains Recovered from Epiphytic and Symptomatic Infections of Maize in Iowa

Clavibacter michiganensis subsp. nebraskensis (Cmn), the causal organism of Goss’s wilt and leaf blight of maize, can be detected in the phyllosphere of its host prior to disease development. We compared the morphology and pathogenicity of 37 putative isolates of Cmn recovered from asymptomatic and symptomatic maize leaves. Thirty-three of the isolates produced mucoid orange colonies, irrespective of the source of isolation and all but four of these isolates were pathogenic on maize. The remaining 4 isolates recovered from asymptomatic leaves had large fluidal yellow colonies, and were non-pathogenic on maize. Isolates varied in their aggressiveness on a susceptible hybrid of maize but no significant differences in aggressiveness were detected between epiphytic isolates and those recovered from diseased maize tissues. The genomics of Cmn is poorly understood; therefore as a first step to determining what genes may play a role in virulence, we compared 33 putative virulence gene sequences from 6 pathogenic and a non-pathogenic isolate recovered from the phyllosphere. Sequence polymorphisms were detected in 5 genes, cellulase A, two endoglucanases, xylanase B and a pectate lyase but there was no relationship with pathogenicity. Further research is needed to determine what genes play a role in virulence of Cmn. Our data show however, that the virulence factors in Cmn likely differ from those reported for the closely related subspecies michiganensis and sepedonicus.     

Fisetin Inhibits Human Melanoma Cell Invasion through Promotion of Mesenchymal to Epithelial Transition and by Targeting MAPK and NFκB Signaling Pathways

Malignant melanoma is responsible for approximately 75% of skin cancer-related deaths. BRAF plays an important role in regulating the mitogen-activated protein kinase (MAPK) signaling cascade in melanoma with activating mutations in the serine/threonine kinase BRAF occurring in 60–70% of malignant melanomas. The BRAF-MEK-ERK (MAPK) pathway is a key regulator of melanoma cell invasion. In addition, activation of NFκB via the MAPK pathway is regulated through MEK-induced activation of IKK. These pathways are potential targets for prevention and treatment of melanoma. In this study, we investigated the effect of fisetin, a phytochemical present in fruits and vegetables, on melanoma cell invasion and epithelial-mesenchymal transition, and delineated the underlying molecular mechanism. Treatment of multiple human malignant melanoma cell lines with fisetin (5–20 µM) resulted in inhibition of cell invasion. BRAF mutated melanoma cells were more sensitive to fisetin treatment, and this was associated with a decrease in the phosphorylation of MEK1/2 and ERK1/2. In addition, fisetin inhibited the activation of IKK leading to a reduction in the activation of the NFκB signaling pathway. Treatment of cells with an inhibitor of MEK1/2 (PD98059) or of NFκB (caffeic acid phenethyl ester) also reduced melanoma cell invasion. Furthermore, treatment of fisetin promoted mesenchymal to epithelial transition in melanoma cells, which was associated with a decrease in mesenchymal markers (N-cadherin, vimentin, snail and fibronectin) and an increase in epithelial markers (E-cadherin and desmoglein). Employing three dimensional skin equivalents consisting of A375 cells admixed with normal human keratinocytes embedded onto a collagen-constricted fibroblast matrix, we found that treatment of fisetin reduced the invasive potential of melanoma cells into the dermis and increased the expression of E-cadherin with a concomitant decrease in vimentin. These results indicate that fisetin inhibits melanoma cell invasion through promotion of mesenchymal to epithelial transition and by targeting MAPK and NFκB signaling pathways.     

Impact of Universal Health Insurance Coverage on Hypertension Management: A Cross-National Study in the United States and England

Background

The Patient Protection and Affordable Care Act (ACA) galvanised debate in the United States (US) over universal health coverage. Comparison with countries providing universal coverage may illustrate whether the ACA can improve health outcomes and reduce disparities. We aimed to compare quality and disparities in hypertension management by socio-economic position in the US and England, the latter of which has universal health care.

Method

We used data from the Health and Retirement Survey in the US, and the English Longitudinal Study for Aging from England, including non-Hispanic White respondents aged 50–64 years (US market-based v NHS) and >65 years (US-Medicare v NHS) with diagnosed hypertension. We compared blood pressure control to clinical guideline (140/90 mmHg) and audit (150/90 mmHg) targets; mean systolic and diastolic blood pressure and antihypertensive prescribing, and disparities in each by educational attainment, income and wealth, using regression models.

Results

There were no significant differences in aggregate achievement of clinical targets aged 50 to 65 years (US market-based vs. NHS- 62.3% vs. 61.3% [p = 0.835]). There was, however, greater control in the US in patients aged 65 years and over (US Medicare vs. NHS- 53.5% vs. 58.2% [p = 0.043]). England had no significant socioeconomic disparity in blood pressure control (60.9% vs. 63.5% [p = 0.588], high and low wealth aged ≥65 years). The US had socioeconomic differences in the 50–64 years group (71.7% vs. 55.2% [p = 0.003], high and low wealth); these were attenuated but not abolished in Medicare beneficiaries.

Conclusion

Moves towards universal health coverage in the US may reduce disparities in hypertension management. The current situation, providing universal coverage for residents aged 65 years and over, may not be sufficient for equality in care.     

Biochemically Triggered Heat and Drought Stress Tolerance in Rice by Proline Application

Journal of Plant Growth Regulation - Abiotic stresses are the prime coercion to sustainable crop production in changing climate scenario. Heat and drought stresses at reproductive as well as...     

Investigation on the Phytochemical Composition,Antioxidant and Enzyme Inhibition Potential of Polygonum Plebeium R.Br: A Comprehensive Approach to Disclose New Nutraceutical and Functional Food Ingredients

The present work describes medicinal potential and secondary metabolic picture of the methanol extract (PP-M) of Polygonum plebeium R.Br. and its fractions; hexane (PP-H), ethyl acetate (PP-E) and water (PP-W). In total bioactive component estimation, highest contents of phenolic (89.38±0.27 mgGAE/g extract) and flavonoid (51.21±0.43 mgQE/g extract) were observed in PP-E, and the same fraction exhibited the highest antioxidant potential in DPPH (324.80±4.09 mgTE/g extract), ABTS (563.18±11.39 mgTE/g extract), CUPRAC (411.33±15.49 mgTE/g extract) and FRAC (369.54±1.70 mgTE/g extract) assays. In Phosphomolybdenum activity assay, PP-H and PP-E showed nearly similar potential, however, PP-H was the most active (13.54±0.24 mgEDTAE/g extract) in metal chelating activity assay. PP-W was the stronger inhibitor (4.03±0.05 mgGALAE/g extract) of the enzyme AChE, while PP-H was potent inhibitor of BChE (5.62±0.27 mg GALAE/g extract). Interestingly, PP-E was inactive against BChE. Against tyrosinase activity, PP-E was again the most active fraction with inhibitory value of 71.89±1.44 mg KAE/g extract, followed by the activity of PP-M and PP-W. Antidiabetic potential was almost equally distributed among PP-M, PP-H and PP-E. For mapping the chemodiversity of P. plebeium, PP-M was analyzed through UHPLC/MS, which led to the identification of more than 50 compounds. Flavonoids were the main components derived from isovitexin, kaempferol and luteolin however, gallic acid, protocatechuic acid, gingerols and lyoniresinol 9′-sulfate were among important bioactive phenols. These findings prompted to conclude that Polygonum plebeium can be a significant source to offer new ingredient for nutraceuticals and functional foods.     

Short term exposure with ultraviolet radiations: A strategy to improve resistance against root-infecting fungi in Luffa cylindrica (L.) Roem

Ultraviolet (UV) radiation is a component of the solar radiations that alter various physiological and biochemical processes in plants. There have been interests in UV-C and UV-B radiations because of their effects on plant physiology. In this study, we investigated the effect of short term UV irradiance on both biochemical parameters and pathogenicity of several root-infecting fungi in Luffa cylindrica. Plant seedlings were exposed once to UV-B and UV-C radiation for 0, 1, 2, 3, 4, and 5 h. After exposure, plant seedlings were transferred to a potting soil that contained natural populations of root-infecting fungi for 30 days. Initially, the plant height and weight enhanced with the increase of exposure time but then plants showed slower growth at the highest time (5 h) of exposure. Colonization of Macrophomina phaseolina, Rhizoctonia solani, and Fusarium species was reduced when plants were exposed to UV radiation at various time intervals. We also found increased levels of chlorophyll ´a`, chlorophyll ‘b’, and carotenoids in plants exposed to radiation. An increase in protein content was also recorded under UV-B and UV-C exposure. Enhanced catalase (CAT) activity was noted after maximum time exposure with UV-C irradiance. Ascorbate peroxidase (APX) activity was increased with the exposure time to UV radiation. We conclude that short time UV irradiation causes alteration in photosynthetic pigments and stress enzymes activities in L. cylindrica that play a major role in the improvement of resistance against root-infecting fungi.     

Signature molecular changes in the skeletal muscle of hindlimb unloaded mice

Hind-limb unloaded (HU) mouse is a well-recognized model of muscle atrophy; however, the molecular changes in the skeletal muscle during unloading are poorly characterized. We have used Raman spectroscopy to evaluate the structure and behavior of signature molecules involved in regulating muscle structural and functional health. The Raman spectroscopic analysis of gastrocnemius muscles was compared between 16-18 weeks old HU c57Bl/6J mice and ground-based controls. The spectra showed that the signals for asparagine and glutamine were reduced in HU mice, possibly indicating increased catabolism. The peaks for hydroxyproline and proline were split, pointing towards molecular breakdown and reduced tendon repair. We also report a consistently increased intensity in> 1300 cm^-1 range in the Raman spectra along with a shift towards higher frequencies in the HU mice, indicating activation of sarcoplasmic reticulum (SR) stress during HU.