Accelerated alveolar bone loss in mice lacking interleukin-10: late onset

OBJECTIVE AND BACKGROUND: Interleukin-10 (IL-10) is an anti-inflammatory cytokine regulating immune responses. We have previously reported that IL-10(-/-) mice experience accelerated alveolar bone loss. The purpose of the present study was to examine the timing of the manifestation of accelerated alveolar bone loss in IL-10(-/-) mice. MATERIALS AND METHODS: Twenty-four IL-10(-/-) and 21 IL-10(+/+) age-matched male 129/SvEv mice were used. Sacrifice times occurred at 1, 3 and 9.5 months of age. Alveolar bone loss was determined morphometrically on defleshed jaws. Enzyme-linked immunosorbent assay (ELISA) was used for determination of serum concentration of type I collagen C-telopeptide, a systemic marker of bone resorption. RESULTS: Alveolar bone loss for the entire IL-10(-/-) group was significantly different than for the IL-10(+/+) group (p = 0.025). There was no significant difference in alveolar bone loss between IL-10(-/-) and IL-10(+/+) mice at 1 and 3 months of age. At 9.5 months of age, IL-10(-/-) mice exhibited 39% greater alveolar bone loss than IL-10(+/+) mice (p = 0.018). For IL-10(-/-) mice, alveolar bone loss significantly increased with age. Serum C-telopeptide levels significantly decreased with age in both groups. IL-10(-/-) mice had consistently higher C-telopeptide levels than IL-10(+/+) mice and the difference between the two groups reached statistical significance (p = 0.011) for the 9.5-month-old mice. CONCLUSIONS: These results suggest that the accelerated alveolar bone loss observed in IL-10(-/-) mice is a late-onset condition and that lack of IL-10 may have an effect on bone homeostasis.     

Addressing methodological issues in studying antidepressant onset efficacy using prespecified sensitivity analyses

Objectives: Assessing antidepressant onset efficacy presents substantial methodological challenges. Most assessments of onset efficacy are based on post hoc analyses. This article presents a case study of a prospectively designed trial to compare antidepressant onset efficacy. Experimental Design: The current study design was compared with previously published criteria for an ideal onset of action study. Prospectively defined sensitivity analyses were used to assess whether results of the present study were influenced by the assumptions and decisions necessary to implement this study. Principal Observations: The study achieved its primary objective of establishing noninferiority between SNRI and SSRI. Sensitivity analyses suggested that results from the primary analysis were not influenced by patient population, outcome measure, cut-off for defining clinically meaningful sustained improvement, or analytical method. Although not all limitations could be addressed, appropriate conclusions could be drawn. For example, the study tested only one fixed dose of each drug; hence, conclusions are limited to those dosages and cannot be extrapolated across the entire dose ranges, as would be possible in the ideal study. Conclusion: This article illustrates that prospectively designed studies (as opposed to retrospective comparisons) can be implemented and sensitivity analyses can be used to address concerns regarding assumptions and arbitrary decisions.     

Successful Hemodialysis Through Persistent Left Superior Vena Cava: a Case Report

Persistent left superior vena cava is an extremely rare venous anomaly affecting 0.5% to 2% of the general population. Persistent left superior vena cava with absent right superior vena cava, also termed as “isolated persistent left superior vena cava.” Persistent left superior vena cava, without associated cardiac anomalies, is usually innocuous. Its discovery, however, has important clinical implications. It can pose clinical difficulties with central venous access, hemodialysis catheter placement, and pacemaker implantation. We hereby present a case of persistent left superior vena cava that was incidentally encountered after the placement of a hemodialysis catheter through the left internal jugular vein. This case highlights the pertinent radiologic findings and emphasizes the importance of familiarity to such an anatomic anomaly.     

Viral hepatitis and HIV in Africa

With increasing access to antiretroviral therapy across sub-Saharan Africa, progress is finally being made in combating the devastating HIV epidemic. As HIV-infected individuals live longer, the effects of coinfection with chronic hepatitis B and C will likely become an increasingly relevant issue. Indeed, HIV adversely affects the natural history of HBV and HCV, both of which are endemic across the African continent, Issues ranging from appropriate diagnostic testing to prevention and treatment are affected by HIV coinfection, particularly in resource-limited settings. In addition, some of the more complex problems such as occult infection, immune reconstitution, and antiretroviral hepatotoxicity are becoming increasingly important considerations. In this review, we present the available data on coinfection in Africa with a major emphasis on prevalence, routes of transmission, prevention and treatment strategies.     

EphA2 Targeting Pegylated Nanocarrier Drug Delivery System for Treatment of Lung Cancer

Purpose

Evaluation of tumor targeting pegylated EphA2 peptide coated nanoparticles (ENDDs) of a novel anticancer agent DIM-C-pPhC₆H₅ (DIM-P) and Docetaxel (DOC) and investigate its antitumor activity and potential for treatment of lung cancer.

Methods

Nanoparticles were prepared with DIM-P and DOC (NDDs) using Nano-DeBEE. ENDDs were prepared by conjugating NDDs with 6His-PEG2K-EphA2 peptide and characterized for physicochemical properties, binding assay, cytotoxicity, cellular uptake studies, drug release and pharmacokinetic parameters. Anti-tumor activity of ENDDs was evaluated using a metastatic H1650 and orthotopic A549 tumor models in nude mice and tumor tissue were analyzed by RT-PCR and immunohistochemistry.

Results

Particle size and entrapment efficiency of ENDDs were 197?±?21 nm and 95?±?2%. ENDDs showed 32.5?±?3.5% more cellular uptake than NDDs in tumor cells. ENDDs showed 23?±?3% and 26?±?4% more tumor reduction compared to NDDs in metastatic and orthotopic tumor models, respectively. In-vivo imaging studies using the Care stream MX FX Pro system showed (p?Conclusions The results emanating from these studies demonstrate anti-cancer potential of DIM-P and the role of ENDDs as effective tumor targeting drug delivery systems for lung cancer treatment.     

Safety of Enteral Feedings in Critically Ill Children Receiving Vasoactive Agents

Background: The objective of this retrospective study was to evaluate the safety of enteral feeding in children receiving vasoactive agents (VAs). Methods: Patients aged 1 month to 18 years with a pediatric intensive care unit stay for ≥96 hours during 2007 and 2008 who received any VA (epinephrine, norepinephrine, vasopressin, milrinone, dopamine, and dobutamine) were included and categorized into fed and nonfed groups. Their demographics, clinical characteristics, type and dose of VA, and presence of gastrointestinal (GI) outcomes were obtained. GI outcomes were compared between the groups by the χ² test, Mann‐Whitney test, and logistic regression. Results: In total, 339 patients were included. Of these, 55% were in the fed group and 45% in the nonfed group. Patients in the fed group were younger (median age, 1.05 vs 2.75 years, respectively; P < .001) and tended to have a lower Pediatric Index of Mortality 2 (PIM2) risk of mortality (ROM) than those in the nonfed group (median, 3.33% vs 3.52%, respectively; P = .106). Mortality was lower in the fed group than the nonfed group (6.9% vs 15.9%, respectively; odds ratio [OR], 0.39; 0.18–0.84; P < .01, 95% CI), while GI outcomes did not differ between the groups. The vasoactive‐inotropic score (VIS) did not differ between the groups except on day 1 (P = .017). The ROM did not differ between the groups after adjusting for age, PIM2 ROM, and VIS on day 1 (OR, 0.58; 0.26–1.28; P = .18, 95% CI). Conclusions: Enteral feeding in patients receiving VAs is associated with no difference in GI outcomes and a tendency towards lower mortality. Prospective studies are required to confirm the safety of enteral feedings in patients receiving VAs.