Short-acting beta-adrenergic blockade and the fetus. A case report.

An infant was born to a woman who received intravenous esmolol for intrapartum supraventricular tachyarrhythmia. Despite the very short acting and cardio-selective beta-1 adrenergic blockade induced by that agent, neonatal effects can occur up to 48 hours after delivery.     

Osteonecrosis of the jaws associated with use of risedronate: report of 2 new cases.

Use of various bisphosphonates has been associated with the development of osteonecrosis of the jaws (ONJ). At least 865 cases of ONJ attributed to these agents have been reported in the English-language literature. Approximately 96% of these published cases were seen with administration of the intravenous agents pamidronate and zoledronate, whereas only 26 cases have been associated with oral bisphosphonates, 25 of them with alendronate. Only a single case of ONJ associated with the oral bisphosphonate risedronate has been previously cited. We report 2 cases of ONJ attributed to risedronate administration. The patients developed osteonecrosis 15 and 24 months after treatment for osteopenia. A regimen of antibiotics and chlorhexidine mouthrinse resolved the osseous defect in the mandible caused by complete exfoliation of a lingual torus in 1 patient. The other patient required sequestrectomy, repeated courses of antibiotics, surgical debridement, and steroids to promote closure of an oroantral fistula and management of sinusitis after bone grafting and implant placement in the posterior maxilla. A demographic profile of reported oral bisphosphonate users affected by ONJ is also provided. With the millions of patients receiving various oral bisphosphonates for osteopenia and osteoporosis, health care practitioners should be aware of the potential for the onset of osteonecrosis and familiar with its management.     

Synthesis and characterization of polyanhydride for local BCNU delivery carriers

p-Carboxyphenoxy propane (CPP) prepolymer consisting of 4 units and sebacic acid (SA) prepolymer consisting of about 10 units were synthesized by reacting CPP and SA in the presence of excess acetic anhydride, respectively. Polyanhydride, poly(CPP-SA) copolymers were copolymerized by a melt polycondensation process with a mixture of CPP and SA prepolymer. Copolymers of average molecular weight up to 110,000 g/mol were achieved. The crystallinity of poly(CPP-SA) copolymers was decreased by the addition of the CPP homopolymer segment to SA homopolymer. Poly(CPP-SA) copolymers gradually degraded for period of 10 days. No large difference of weight loss observed according to molecular weight variation of poly(CPP-SA) copolymers. BCNU release from wafers fabricated by poly(CPP-SA) showed a sustained release pattern with no initial burst and delay of drug release.     

Thermal preference behavior in preweaning genetically obese (ob/ob) and lean (+/?, +/+) mice

Impaired nonshivering thermogenesis and lowered rectal temperatures (Tre) are hallmarks that appear early in the postnatal ontogeny of the genetically obese (ob/ob) mouse. Adult obese mice compensate behaviorally for these impairments and do not defend their low Tres. We predicted that, because young mice primarily rely on behavior to ensure thermal homeostasis during preweaning development, the appearance of the obese mouse's thermoregulatory impairment should promote their continued reliance on behavioral thermoregulation compared to lean pups. Accordingly, intact litters of pups from heterozygous lean (C57BL/6J, ob/+) and from homozygous lean (+/+) matings were tested at 6, 12, and 18 days postpartum on a thermal gradient (14-44 degrees C). Obese pups had lower pretest Tres than lean (+/?) littermates at 6 days and lower pretest Tres than both lean littermates and homozygous (+/+) lean control pups at 12 and 18 days. Exposure to the gradient ameliorated these differences (i.e., no posttest Tre differences among phenotypes). Correspondingly, obese pups preferred warmer gradient locations than +/+ pups but similar locations to their phenotypically lean (+/?) littermates until 18 days, when both lean groups preferred similar thermal locations compared to warmer-seeking obese pups. These data support our hypothesis and emphasize the age-dependent impact of the ob gene on altering mouse pups' thermal preferences.     

Noninvasive in vivo magnetic resonance imaging of injury-induced neointima formation in the carotid artery of the apolipoprotein-E null mouse

Mice deficient in apolipoprotein-E (apoE) experience severe hypercholesterolemia, are prone to atherosclerosis, and recently have emerged as a powerful tool in the study of plaque formation. In this study, we developed magnetic resonance (MR) imaging methods to detect the progression of atherosclerosis noninvasively in a mouse model of arterial injury. Four 14-week-old apoE-deficient mice were imaged 5 weeks after beginning an atherogenic Western diet and 4 weeks after wire denudation injury of the left common carotid artery (LCCA). Information from several images was combined into high-information content images using methods previously developed. The image resolution was 47 x 47 x 750 microm(3). We acquired T1-, T2-, and proton density (PD)-weighted images (TR/TE 650/14, 2000/60, and 2000/14 msec, respectively). Each 8-bit image was placed in a separate color channel to produce a 24-bit color image (red = T1, green = PD, and blue = T2). The composite image created contrast between different tissue types that was superior to that of any single image and revealed significant luminal narrowing of the LCCA, but not the uninjured RCCA. MR images were compared with corresponding histopathology cross sections and luminal area measurements from each method correlated(r2= 0.61). Atherosclerotic luminal narrowing was successfully detected through MR imaging in a mouse model of arterial injury that is small, reproduces quickly, and lends itself to genetic analysis and manipulation.     

A Raman spectroscopic study of the diclofenac sodium–β-cyclodextrin interaction

The inclusion complex of diclofenac sodium (DCFNa) and β-cyclodextrin (βCD) was prepared and analyzed by using Raman and SERS spectroscopy. The interaction between DCFNa and βCD molecules was evidenced by monitoring the change in the peak positions and the widths of some guest molecule bands relative to those observed in the spectra of the free compound and 1:1 DCFNa–βCD physical mixture. Raman data have shown that the interaction between the guest and host molecules in the 1:1 DCFNa–βCD complex is maintained both through the dichlorophenyl ring and the phenylacetate group. SER spectra revealed that depending on the pH value of the solution different isomeric forms of the 1:1 guest–host complex are preferentially adsorbed on the silver surface via the nonbonding electrons of the oxygen atom. The orientation of the adsorbed species with respect to the metal surface was also elucidated.     

Milk derived colloid as a novel drug delivery carrier for breast cancer

Triple negative breast cancer has an extremely poor prognosis when chemotherapy is no longer effective. To overcome drug resistance, novel drug delivery systems based on nanoparticles have had remarkable success. We produced a novel nanoparticle component ‘MDC’ from milk-derived colloid. In order to evaluate the anti-cancer effect of MDC, we conducted in vitro and in vivo experiments on cancer cell lines and a primary tumor derived breast xenograft. Doxorubicin (Dox) conjugated to MDC (MDC-Dox) showed higher cancer cell growth inhibition than MDC alone especially in cell lines with high EGFR expression. In a mouse melanoma model, MDC-Dox significantly suppressed tumor growth when compared with free Dox. Moreover, in a primary tumor derived breast xenograft, one of the mice treated with MDC-Dox showed partial regression, while mice treated with free Dox failed to show any suppression of tumor growth. We have shown that a novel nanoparticle compound made of simple milk-derived colloid has the capability for drug conjugation, and serves as a tumor-specific carrier of anti-cancer drugs. Further research on its safety and ability to carry various anti-cancer drugs into multiple drug-resistant primary breast models is warranted.