Cross‐sectional assessment of pain and physical function in skeletal dysplasia patients

Short stature skeletal dysplasia (SD) patients have orthopedic and neurologic complications causing significant pain and physical disability. We conducted a large cross‐sectional online survey in 361 people with short stature SD (>10 years) to describe pain prevalence, characteristics, and the relationship between pain and function. Chronic pain prevalence per Brief Pain Inventory (BPI) was 70.3%. Women reported more pain than men (73% vs 63% p = 0.04). Pain Severity Score (average of current, worst, least and average pain) averaged 3.3 ± 2, while the Pain Interference Score (with daily activities) averaged 3.4 ± 2.7 on a 10‐point scale. Per Bleck scale, 20.5% had little or no functional capacity. Increasing age and decreased ambulation independently predicted chronic pain. Chronic pain is prevalent in short stature SD patients and associated with poor physical function. Further study is required to clarify the temporal relationship among pain, function and treatments.     

Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells

Resveratrol (RL), a natural polyphenol, is known for its diverse biological effects against various human cancer cell lines. But low aqueous solubility, poor bioavailability, and stability limit its efficacy against prostate cancer. In this study polymeric nanoparticles encapsulating resveratrol (RLPLGA) were designed and their cytotoxic and mode of apoptotic cells death against prostate cancer cell line (LNCaP) was determined. Nanoparticles were prepared by solvent displacement method and characterized for particle size, TEM, entrapment efficiency, DSC and drug release study. RLPLGA exhibited a significant decrease in cell viability with 50% and 90% inhibitory concentration (IC₅₀ and IC₉₀) of 15.6?±?1.49 and 41.1?±?2.19?μM respectively against the LNCaP cells. This effect was mediated by apoptosis as confirmed by cell cycle arrest at G1-S transition phase, externalization of phosphatidylserine, DNA nicking, loss of mitochondrial membrane potential and reactive oxygen species generation in LNCaP cells. Furthermore, significantly greater cytotoxicity to LNCaP cells was observed with nanoparticles as compared to that of free RL at all tested concentrations. RLPLGA nanoparticles presented no adverse cytotoxic effects on murine macrophages even at 200?μM. Our findings support the potential use of developed resveratrol loaded nanoparticle for the prostate cancer chemoprevention/ chemotherapy with no adverse effect on normal cells.     

Two-stage mass spectrometry approach for the analysis of triterpenoid glycosides in Fagonia indica

Triterpenoid glycosides are molecules widely distributed in plants and have shown a wide range of biological activities against various diseases. This paper describes the qualitative and quantitative analysis of triterpenoid glycoside (saponins) using a two-stage mass spectrometry approach in five samples of Fagonia indica collected from various parts of the country. In the first stage, triterpenoid glycosides were identified using liquid chromatography high-resolution mass spectrometry using UHPLC-QTOF-MS system. In the second stage, compounds were quantified using a multiple reaction monitoring (MRM) approach using an UHPLC-QQQ-MS system. Fagonia indica has shown a wide range of biological activities and found to be rich in saponin or triterpenoid glycoside constituents. A total of thirteen triterpenoid saponins were identified based on high-resolution analysis, MS/MS and database comparison, while six of them were simultaneously quantified using the multiple reaction monitoring (MRM) approach. The results indicate that the samples share a similar UHPLC pattern, however, the amount of these saponins in samples varies greatly. Compound 4i.e. nayabin D was the major constituent (1.4–3.8 μg g⁻¹) among the six analyzed compounds. The results demonstrated that the developed multi-compound determination in combination with a fingerprint analysis method is rapid, accurate, precise and sensitive and can be utilized for quality control and high-throughput quantification of various saponins in Fagonia indica may be extended to other plant species.

Development of a rapid, accurate, precise, and effective method for the analysis and quantification of saponins in crude extracts from Fagonia indica.     

Diversity of carbapenemases in clinical isolates: The emergence of blaVIM-5 in Bangladesh

Global emergence and dissemination of carbapenemases are clinically threatening, notably in countries with endemic bla_NDM. To analyze the extent of carbapenemases in Bangladesh, 71 isolates were collected from 7 different clinical sources: wound swab (n = 38), pus (n = 13), urine (n = 9), blood (n = 4), tracheal aspirate (n = 3), pleural fluid (n = 1) and vaginal swab (n = 3) from Dhaka Medical College Hospital, Bangladesh. Among the isolates, 25 were resistant to at least one of the three carbapenems (imipenem, meropenem and doripenem), including 15 being resistant to all. These resistant isolates were identified as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, P. hibiscicola, Proteus mirabilis, Providencia stuartii and Citrobacter sedlakii. Carbapenemase detection among these 25 isolates varied in individual phenotypic assays (83% in Modified Hodge Test, 50% in Combined Disk Test for Metallo-β-lactamase prediction) as compared with the genotypes observed (96% prevalence of various carbapenemases including bla_OXA-1,48, bla_NDM-1,5, bla_VIM-2,5). bla_OXA-48 was the most prevalent gene (84%) followed by bla_NDM (72%). Coexistence of multiple gene combination such as bla_NDM+bla_OXA-48+bla_OXA-1 was prevalent (48%). Harborage of bla_VIM-5 (n = 1) was characterized for the first time, while bla_NDM-5 (n = 5) was reported contemporarily with a recent study in Bangladesh. Presence of plasmids (64%) and integron class 1 (100%) signifies the transferable potential of resistant traits. The emergence of such new variants along with the presence of the mobile genetic elements demands strict surveillance and combating strategies.     

trans‐resveratrol alone and hydroxystilbenes of rhubarb (Rheum rhaponticum L.) root reduce liver damage induced by chronic ethanol administration: a comparative study in mice

The hepatoprotective effects and pharmacokinetics of trans‐resveratrol and hydroxystilbenes of the garden rhubarb (Rheum rhaponticum L., R. rhaponticum) root ethanol extract were studied. Ethanol was administered to male BALB/c mice for 35 days in an inhalation chamber. During this time vehicle, trans‐resveratrol (20 mg/kg per day) or R. rhaponticum extract was intraperitoneally (i.p.) administered and mice were sacrificed for the collection of liver and blood. In an additional experiment, the level of parent compounds and metabolites was estimated in the blood after acute i.p. administration of trans‐resveratrol or R. rhaponticum extract. The levels of hydroxystilbenes, their metabolites and fatty acid oxy‐metabolites (oxylipins) were studied by LC‐tandem DAD‐MS/MS. Ethanol induced hepatotoxicity, as evidenced by histological changes and accumulation of oxylipins in the blood. Both trans‐resveratrol and R. rhaponticum extract reduced the extent of these changes. The pharmacokinetics of trans‐resveratrol was characterized by a rapid removal from the blood and metabolism to sulfates and glucuronides. After the administration of R. rhaponticum extract, in addition to trans‐resveratrol glucoside and its metabolites, several other hydroxystilbenes were found. Inhibition of oxidation of polyunsaturated fatty acids is proposed as a basis of the hepatoprotective effect of both trans‐resveratrol and R. rhaponticum extract. Copyright © 2008 John Wiley & Sons, Ltd.