Effects of hydroxypropyl-beta-cyclodextrin on the chemical stability and the aqueous solubility of thalidomide enantiomers

The aim of this work was to study the effect of hydroxypropyl-beta-cyclodextrin on the solubility and stability of thalidomide enantiomers in aqueous solutions for clinical oral administration to be used in HIV-infected children. For this reason racemic thalidomide was added to solutions containing different concentrations of hydroxypropyl-beta-cyclodextrin. True complexes were obtained by using hydroxypropyl-beta-cyclodextrin and the solubility of both thalidomide enantiomers was increased directly depending on the amount of hydroxylpropyl-beta-cyclodextrin in the medium although no enantioselective differences were observed at 37 degrees C. The chemical stability of thalidomide enantiomers is clearly improved by hydroxypropyl-beta-cyclodextrin. No enantioselective degradation of thalidomide was observed in sodium chloride solution (0.9%) samples stored at 6 degrees C for nine days when hydroxypropyl-beta-cyclodextrin was employed as excipient. Therefore a thalidomide solution suitable for oral administration can be prepared by adding hydroxypropyl-beta-cyclodextrin at 10% (w/v).     

Discordance between IgA Switching at the DNA Level and IgA Expression at the mRNA Level in IgA-Deficient Patients

IgA deficiency is a common immune disorder in Caucasians and is associated with certain MHC conserved extended haplotypes, such as [HLA-B8, SC01, DR3], which presumably carry a susceptibility gene(s). We applied a competitive digestion-circularization PCR method to quantitate the number of switch (S)mu to S alpha rearrangements in peripheral B cells from IgA-deficient subjects homozygous for this haplotype and compared their number with the productive C alpha mRNA level to determine C alpha gene expression in IgA-switched B cells. Two types of defects, low expression of both secreted and membrane forms of productive C alpha mRNA in IgA-switched B cells and impaired IgA switching, were characterized in IgA-deficient subjects homozygous for [HLA-B8, SC01, DR3]. The former defect was also found in another noncarrier subject. It may directly cause low IgA secretion and reflects a blockade in post-IgA switch differentiation of B cells. These results suggest that the heterogeneity of defects in IgA deficiency is not simply ascribable to MHC susceptibility genes.     

Correlates of Perinatal Post-Traumatic Stress among Culturally Diverse Women with Depressive Symptomatology

Post-traumatic stress disorder (PTSD) is an important and often neglected comorbidity of pregnancy; left untreated, it can lead to serious health complications for the mother and developing fetus. Structured interviews were conducted to identify risk factors of PTSD among culturally diverse women with depressive symptomatology receiving perinatal services at community obstetric/gynecologic clinics. Women abused as adults, with two or more instances of trauma, greater trauma severity, insomnia, and low social support were more likely to present perinatal PTSD symptoms. Perinatal PTSD is prevalent and has the potential for chronicity. It is imperative healthcare providers recognize salient risk factors and integrate culturally sensitive screening, appropriate referral, and treatment services for perinatal PTSD.     

MRI fused with prone FDG PET/CT improves the primary tumour staging of patients with breast cancer

Objective

Our aim was to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) fused with prone 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in primary tumour staging of patients with breast cancer.

Methods

This retrospective study evaluated 45 women with 49 pathologically proven breast carcinomas. MRI and prone PET-CT scans with time-of-flight and point-spread-function reconstruction were performed with the same dedicated breast coil. The studies were assessed by a radiologist and a nuclear medicine physician, and evaluation of fused images was made by consensus. The final diagnosis was based on pathology (90 lesions) or follow-up?≥?24 months (17 lesions).

Results

The study assessed 72 malignant and 35 benign lesions with a median size of 1.8 cm (range 0.3–8.4 cm): 31 focal, nine multifocal and nine multicentric cases. In lesion-by-lesion analysis, sensitivity, specificity, positive and negative predictive values were 97%, 80%, 91% and 93% for MRI, 96%, 71%, 87%, and 89% for prone PET, and 97%. 94%, 97% and 94% for MRI fused with PET. Areas under the curve (AUC) were 0.953, 0.850, and 0.983, respectively (p?<?0.01).

Conclusions

MRI fused with FDG-PET is more accurate than FDG-PET in primary tumour staging of breast cancer patients and increases the specificity of MRI.

Key points

? FDG PET-CT may improve the specificity of MRI in breast cancer staging.? MRI fused with prone 2-[fluorine-18]-fluoro-2-deoxy-D-glucose PET-CT has better overall diagnostic performance than MRI.? The clinical role of fused PET-MRI has not yet been established.

     

Infection of human fallopian tube epithelial cells with Neisseria gonorrhoeae protects cells from tumor necrosis factor alpha-induced apoptosis

Following infection with Neisseria gonorrhoeae, bacteria may ascend into the Fallopian tubes (FT) and induce salpingitis, a major cause of infertility. In the FT, interactions between mucosal epithelial cells and gonococci are pivotal events in the pathogen's infection cycle and the inflammatory response. In the current study, primary FT epithelial cells were infected in vitro with different multiplicities of infection (MOI) of Pil+ Opa+ gonococci. Bacteria showed a dose-dependent association with cells and induced the secretion of tumor necrosis factor alpha (TNF-alpha). A significant finding was that gonococcal infection (MOI = 1) induced apoptosis in approximately 30% of cells, whereas increasing numbers of bacteria (MOI = 10 to 100) did not induce apoptosis. Apoptosis was observed in only 11% of cells with associated bacteria, whereas >84% of cells with no adherent bacteria were apoptotic. TNF-alpha was a key contributor to apoptosis, since (i) culture supernatants from cells infected with gonococci (MOI = 1) induced apoptosis in na?ve cultures, suggesting that a soluble factor was responsible; (ii) gonococcal infection-induced apoptosis was inhibited with anti-TNF-alpha antibodies; and (iii) the addition of exogenous TNF-alpha induced apoptosis, which was inhibited by the presence of increasing numbers of bacteria (MOI = 10 to 100). These data suggest that TNF-alpha-mediated apoptosis of FT epithelial cells is likely a primary host defense mechanism to prevent pathogen colonization. However, epithelial cell-associated gonococci have evolved a mechanism to protect the cells from undergoing TNF-alpha-mediated apoptosis, and this modulation of the host innate response may contribute to establishment of infection. Understanding the antiapoptotic mechanisms used by Neisseria gonorrhoeae will inform the pathogenesis of salpingitis and could suggest new intervention strategies for prevention and treatment of the disease.     

Liver radioembolization using 90 y resin microspheres in elderly patients: tolerance and outcome

Purpose Yttrium 90 (90 Y) microsphere radioembolization (90 Y-RE) is an emerging locoregional treatment for liver cancer. The most common complications of 90 Y-RE arise from excessive irradiation of nontarget organs (eg, gastrointestinal tract, lung, and nontumoral liver). Patients with advanced age may have substantial comorbidities that can affect their life expectancy, and tolerance to radiation in elderly patients may be altered. The purpose of this study is to evaluate the safety and survival of elderly patients treated with 90 Y-RE. Materials and Methods We analyzed 255 patients with liver tumors (primary or metastatic) who were treated with 90 Y-RE in our institution from September 2003 to February 2010. We categorized patients as "elderly" if aged ≥ 70 years and "younger" if aged < 70 years. Results Seventy-three patients (29%) were aged ≥ 70 years. The most frequent liver tumor among elderly patients was hepatocellular carcinoma. Complication rates were similar in both groups: 10.4% of elderly patients and 9.9% of younger patients developed radioembolization-induced liver disease (P = 1.000). Only 1.5% of elderly patients developed gastrointestinal ulceration and no patient in the elderly group developed pneumonitis. The median overall survival of patients with hepatocellular carcinoma was similar in elderly and younger groups (13 months, 95% confidence interval [CI], 10.4-15.5 and 12 months, 95% CI, 4.2-15.7; P = 0.4). In patients with colorectal carcinoma metastatic to the liver, the median overall survival was 10 months (95% CI, 5.2-14.7) for elderly patients and 13 months (95% CI, 7.0-18.9) for younger patients (P = 0.3). The median overall survival of patients with other histologies was 9 months (95% CI, 3.5-14.4) for younger patients and 4 months (95% CI, 2.7-5.2) for elderly patients (P = 0.9). Conclusion Elderly patients did not have more toxicity than younger patients treated with 90 Y-RE, and survival was similar for each histology. Elderly patients should be considered for 90 Y-RE if they otherwise meet the inclusion criteria applicable to younger patients.