Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Received: 12 September 2001 / Accepted: 11 December 2001     

Oxazoline scaffold in synthesis of benzosiloxaboroles and related ring-expanded heterocycles: diverse reactivity,structural peculiarities and antimicrobial activity

Two isomeric benzosiloxaborole derivatives 3a and 5a bearing fluorine and 4,4-dimethyl-2-oxazolin-2-yl substituents attached to the aromatic rings were obtained. Both compounds were prone to hydrolytic cleavage of the oxazoline ring after initial protonation or methylation of the nitrogen atom. The derivative 3c featuring N-methylammoniumalkyl ester functionality was successfully subjected to N-sulfonylation and N-acylation reactions to give respective derivatives which demonstrates its potential for modular synthesis of structurally extended benzosiloxaboroles. Compound 5c bearing N-ammoniumalkyl ester underwent conversion to a unique macrocyclic dimer due to siloxaborole ring opening. Furthermore, an unexpected 4-electron reduction of the oxazoline ring occurred during an attempted synthesis of 5a. The reaction gave rise to an unprecedented 7-membered heterocyclic system 4a comprising a relatively stable B–O–B–O–Si linkage and stabilized by an intramolecular N–B coordination. It could be cleaved to derivative 4c bearing BOH and SiMe₂OH groups which acts as a pseudo-diol as demonstrated by formation of an adduct with Tavaborole. Apart from the multinuclear NMR spectroscopy characterization, crystal structures of the obtained products were determined in many cases by X-ray diffraction. Investigation of biological activity of the obtained compounds revealed that derivatives 3e and 3f with pendant N-methyl arylsulfonamide groups exhibit high activity against Gram-positive cocci such as methicillin-sensitive Staphylococcus aureus ATCC 6538P, methicillin-resistant S. aureus (MRSA) ATCC 43300 as well as the MRSA clinical strains, with MIC values in the range of 3.12–6.25 mg L⁻¹. These two compounds also showed activity against Enterococcus faecalis ATCC 29212 and Enterococcus faecium ATCC 6057 (with MICs of 25–50 mg L⁻¹). The results of the antimicrobial activity and cytotoxicity studies indicate that 3e and 3f can be considered as potential antibacterial agents, especially against S. aureus MRSA.

Transformations of oxazoline–benzosiloxaborole conjugates gave rise to novel boracyclic systems as well as functionalized derivatives featuring antibacterial activity.     

The toxicity of cationic surfactants in four bioassays

The purpose of this study was to investigate the toxicity of 15 quaternary ammonium compounds (QACs) in a battery of four bioassays comprising the bacterium Vibrio fischeri, two ciliated protozoa Spirostomum ambiguum and Tetrahymena thermophia, and the anostracean crustacean Artemia franciscana. The compounds were prepared by Professor Pernak's group at Poznań University of Technology (Poland). The toxicity of the test compounds was very high, with EC(LC)(50) values varying from 0.11 to 70 micromol/L. Microtox was the most sensitive bioassay, while the crustacean test was the least sensitive. Among the protozoa T. thermophila was 5-30 times less sensitive than S. ambiguum. The toxicity of the QACs depended on their structure, but no simple correlation was found for all the bioassays applied.     

The Influence of Intensive Nutritional Education on the Iron Status in Infants

Iron is an essential nutrient for a child’s proper development at every growth stage. It is crucial for the production of red blood and muscle cells, DNA replication, and the development of the brain, nervous and immune systems. Iron deficiency is the most common micronutrient deficiency in children worldwide. Despite widespread access to nutritional information for children, parents continue to make many feeding mistakes. This study aimed to assess whether any nutritional intervention would affect the iron status in children. The parents of 203 children were randomly assigned to one of two groups: the study group received intensive mobile nutritional education for a year, while the control group received no intervention. Blood tests were performed on both groups at the beginning of the study and one year later. The educational intervention resulted in statistically significantly higher levels of RBC (red blood cells; p = 0.020), HGB (haemoglobin; p = 0.039), HCT (haematocrit; p = 0.036), MCV (mean cell volume; p = 0.018) parameters and iron dietary intake (p ≤ 0.001). Even a non-targeted dietary intervention improves the iron status in children. As iron management is insufficient in most children, an iron-targeted nutritional intervention appears necessary.     

Spatial and seasonal variability of the mass concentration and chemical composition of PM2.5 in Poland

The seasonal changes in ambient mass concentrations and chemical composition of fine particulate matter (PM_2.5) were investigated in three locations in Poland. The analyses included PM_2.5-bound hazardous benzo(a)pyrene (BaP), As, Ni, Cd, and Pb. The samples of PM_2.5 were collected daily in Katowice (southern Poland, urban background site), Gdańsk, and Diabla Góra (northern Poland, urban and regional background sites, respectively) during 1-year-long campaign in 2010. Based on monthly ambient concentrations of PM_2.5-bound carbon (organic and elemental), water-soluble ions (Na⁺, NH₄ ⁺, K⁺, Mg²⁺, Ca²⁺, Cl^?, NO₃ ^?, SO₄ ^2?), and elements As, Ni, Cd, Pb, Ti, Al, Fe, the chemical mass closure of PM_2.5 was checked for each of the four seasons of the year and for the heating and non-heating periods at each site. Also, the annual concentrations of PM_2.5 were determined and the annual PM_2.5 mass closure checked. At each measuring point, the PM_2.5 concentrations were high compared to its Polish yearly permissible value, 25 μg/m³, and its concentrations elsewhere in Europe. The highest annual PM_2.5 concentration, 43 μg/m³, occurred in Katowice; it was twice the annual PM_2.5 concentration in Gdańsk, and thrice the one in Diabla Góra. The high annual averages were due to very high monthly concentrations in the heating period, which were highest in the winter. PM_2.5 consisted mainly of carbonaceous matter (elemental carbon (EC) + organic matter (OM), the sum of elemental carbon, EC, and organic matter, OM; its annual mass contributions to PM_2.5 were 43, 31, and 33 % in Katowice, Gdansk, and Diabla Góra, respectively), secondary inorganic aerosol (SIA), the Na_Cl group, and crustal matter (CM)—in the decreasing order of their yearly mass contributions to PM_2.5. OM, EC, SIA, Na_Cl, and CM accounted for almost 81 % of the PM_2.5 mass in Katowice, 74 % in Gdańsk, and 90 % in Diabla Góra. The annual average toxic metal contribution to the PM_2.5 mass was not greater than 0.2 % at each site. In Katowice and Gdańsk, the yearly ambient BaP concentrations were high (15.4 and 3.2 ng/m³, respectively); in rural Diabla Góra, the concentrations of BaP were almost equal to 1 ng/m³, the Polish BaP annual limit. The great seasonal fluctuations of the shares of the component groups in PM_2.5 and of the concentrations of PM_2.5 and its components are due to the seasonal fluctuations of the emissions of PM and its precursors from hard and brown coal combustion for energy production, growing in a heating season, reaching maximum in winter, and decreasing in a non-heating period. In Gdańsk, northern Poland, especially in the spring and autumn, sea spray might have affected the chemical composition of PM_2.5. The greatest hazard from PM_2.5 occurs in Katowice, southern Poland, in winter, when very high concentrations of PM_2.5 and PM_2.5-related carbonaceous matter, including BaP, are maintained by poor natural ventilation in cities, weather conditions, and the highest level of industrialization in Poland. In less industrialized northern Poland, where the aeration in cities is better and rather gaseous than solid fuels are used, the health hazard from ambient PM_2.5 is much lower.     

The chicken chorioallantoic membrane model in biology,medicine and bioengineering

The chicken chorioallantoic membrane (CAM) is a simple, highly vascularized extraembryonic membrane, which performs multiple functions during embryonic development, including but not restricted to gas exchange. Over the last two decades, interest in the CAM as a robust experimental platform to study blood vessels has been shared by specialists working in bioengineering, development, morphology, biochemistry, transplant biology, cancer research and drug development. The tissue composition and accessibility of the CAM for experimental manipulation, makes it an attractive preclinical in vivo model for drug screening and/or for studies of vascular growth. In this article we provide a detailed review of the use of the CAM to study vascular biology and response of blood vessels to a variety of agonists. We also present distinct cultivation protocols discussing their advantages and limitations and provide a summarized update on the use of the CAM in vascular imaging, drug delivery, pharmacokinetics and toxicology.     

Functionalization of α-hydroxyphosphonates as a convenient route to N-tosyl-α-aminophosphonates

Direct conversion of the α-hydroxyl group by para-toluenesulfonamide to yield α-(N-tosyl)aminophosphonates is reported. α-Aminophosphonates 23a,b–37a,b were obtained from the corresponding α-hydroxyphosphonates 6a,b–21a,b in the presence of K₂CO₃, via the retro-Abramov reaction of the appropriate aldehydes, 1–5. The subsequent formation of imines with simultaneous addition of diethyl phosphite provided access to the α-sulfonamide phosphonates 23a,b–37a,b with better diastereoselectivity than in the case of the Pudovik reaction. The mechanism for this transformation is proposed herein. When Cbz N-protected aziridine 9a,b and phenylalanine analogue 12a,b were exploited, intramolecular substitution was observed, leading to the corresponding epoxide 38 as the sole product, or oxazolidin-2-one 39 as a minor product. Analogous substitution was not observed in the case of proline 18a,b and serine 21a,b derivatives.

The reaction mechanism and diastereoselectivity of the direct transformation of α-hydroxyphosphonates 6a,b–21a,b by para-toluenesulfonamide, yielding α-(N-tosyl)aminophosphonates 23a,b–37a,b under K₂CO₃ conditions are presented.     

Tolerability of risedronate in postmenopausal women intolerant of alendronate

Bisphosphonates are effective treatments for osteoporosis, but some have been associated with upper gastrointestinal intolerance. This randomized, double-blind study assessed the upper gastrointestinal tolerability of risedronate in postmenopausal women who had discontinued alendronate treatment because of upper gastrointestinal adverse events. Sixty-six women who had previously discontinued treatment with alendronate 10 mg/day because of upper gastrointestinal symptoms received placebo (N=31) or risedronate 5 mg (N=35) daily for 3 months. The primary outcome was the rate of discontinuation due to upper gastrointestinal adverse events: 5/31 (16.1%) in the placebo group, and 4/35 (11.4%) in the risedronate group. Discontinuation rates were also similar in the two treatment groups among subgroups of patients with a history of gastrointestinal disorder, prior use of acid suppression drugs, and concomitant use of NSAIDs. The overall incidence of upper gastrointestinal events was comparable between the placebo (19.4%) and risedronate (20.0%) groups. Overall, risedronate 5 mg/day for 3 months was as well tolerated as placebo in patients who could not tolerate alendronate 10 mg. These results are consistent with, and complement those from previous studies showing that risedronate 5 mg has a gastrointestinal tolerability similar to that of placebo.