Does Oil Rich in Alpha-Linolenic Fatty Acid Cause the Same Immune Modulation as Fish Oil in Walker 256 Tumor-Bearing Rats?

Objective: Polyunsaturated fatty acids n-3 (PUFA n-3) have shown effects in reducing tumor growth, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) abundantly present in fish oil (FO). When these fatty acids are provided in the diet, they alter the functions of the cells, particularly in tumor and immune cells. However, the effects of α-linolenic fatty acid (ALA), which is the precursor of EPA and DHA, are controversial. Thus, our objective was to test the effect of this parental fatty acid. Methods: Non-tumor-bearing and tumor-bearing Wistar rats (70 days) were supplemented with 1 g/kg body weight of FO or Oro Inca® (OI) oil (rich in ALA). Immune cells function, proliferation, cytokine production, and subpopulation profile were evaluated. Results: We have shown that innate immune cells enhanced phagocytosis capacity, and increased processing and elimination of antigens. Moreover, there was a decrease in production of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6)) by macrophages. Lymphocytes showed decreased proliferation capacity, increased cluster of differentiation 8 (CD8⁺) subpopulation, and increased TNF-α production. Conclusions: Oil rich in ALA caused similar immune modulation in cancer when compared with FO.     

Protection and Repair After Spinal Cord Injury: Accomplishments and Future Directions

It was an honor for me to present the 2014 G. Heiner Sell Memorial Lecture at the annual American Spinal Injury Association (ASIA) meeting in San Antonio. For this purpose, I provided a comprehensive review of the scope of research targeting discovery and translational and clinical investigations into spinal cord injury (SCI) research. Indeed, these are exciting times in the area of spinal cord research and clinical initiatives. Many laboratories and clinical programs throughout the world are publishing data related to the pathophysiology of SCI and new strategies for protecting and promoting recovery in both animal models and humans. For this lecture, several topics were discussed including neuroprotective and reparative strategies, neurorehabilitation, quality of life issues, and future directions. In the area of neuroprotection, pathophysiological events that may be targeted with therapeutic strategies, including pharmacological and targeted temperature management were reviewed. For reparative approaches, the importance of both intrinsic and extrinsic mechanisms of axonal regeneration was highlighted. Various cell therapies currently being tested in preclinical and clinical arenas were reviewed as well as ongoing US Food and Drug Administration approved trials for SCI patients. Neurorehabilitation is an evolving research field with locomotive training strategies, electrical stimulation, and brain-machine interface programs targeting various types of SCI. The importance of testing combination approaches including neuroprotective, reparative, and rehabilitative strategies to maximize recovery mechanisms was therefore emphasized. Finally, quality of life issues that affect thousands of individuals living with paralysis were also presented. Future directions and specific obstacles that require attention as we continue to move the SCI field forward were discussed.     

Use of a geographic information system to track smelter-related lead exposures in children: North Lake Macquarie, Australia, 1991–2002

Background  

To determine patterns of childhood lead exposure in a community living near a lead and zinc smelter in North Lake Macquarie, Australia between 1991 and 2002.     

Systematic review of methods to diagnose infection in foot ulcers in diabetes.

AIM: To undertake a systematic review of the diagnostic performance of clinical examination, sample acquisition and sample analysis in infected foot ulcers in diabetes. METHODS: Nineteen electronic databases plus other sources were searched. To be included, studies had to fulfil the following criteria: (i) compare a method of clinical assessment, sample collection or sample analysis with a reference standard; (ii) recruit diabetic individuals with foot ulcers; (ii) present 2 x 2 diagnostic data. Studies were critically appraised using a 12-item checklist. RESULTS: Three eligible studies were identified, one each on clinical examination, sample collection and sample analysis. For all three, study groups were heterogeneous with respect to wound type and a small proportion of participants had foot ulcers due to diabetes. No studies identified an optimum reference standard. Other methodological problems included non-blind interpretation of tests and the time lag between index and reference tests. Individual signs or symptoms of infection did not prove to be useful tests when assessed against punch biopsy as the reference standard. The wound swab did not perform well when assessed against tissue biopsy. Semiquantitative analysis of wound swab might be a useful alternative to quantitative analysis. The limitations of these findings and their impact on recommendations from relevant clinical guidelines are discussed. CONCLUSION: Given the importance of this topic, it is surprising that only three eligible studies were identified. It was not possible to describe the optimal methods of diagnosing infection in diabetic patients with foot ulceration from the evidence identified in this systematic review.     

Immunity after treatment of human schistosomiasis mansoni. III. Long-term effects of treatment and retreatment

Group mean Schistosoma mansoni reinfection patterns are presented for 2 years after treatment with oxamniquine in 1981 of over 100 9- to 16-year-old Kenyan schoolchildren, and for one year after retreatment in 1983 with either oxamniquine or praziquantel when most (nearly 700) infected people in the whole community were treated. Quality control confirmed comparable Kato egg counts throughout the study. Continuing transmission after 1981 raised prevalence to nearly its original level within 6 months, but intensity remained suppressed throughout the 2 year follow-up and very few children reacquired heavy infections (greater than 400 eggs/g). Age and sex had significant effects: reinfection diminished with age, especially among boys--a pattern not apparently attributable to differential water contact. Children with heavy pretreatment infections tended to develop heavy reinfections but this trend was not statistically significant on a group basis, nor were similar trends during the period of less pronounced transmission following the 1983 community treatment. Oxamniquine was equally effective in children receiving it in both 1981 and 1983, and the efficacy of praziquantel resembled that of oxamniquine. In this area of Kenya, repeated chemotherapy will be needed to contain transmission, probably annually or biennially, unless supplemented with other, effective control measures. These findings confirm the beneficial effects of treating even a limited segment of a community at intervals of a year or more without necessarily stopping transmission. They are also compatible with recent findings on potential immune mechanisms in man.     

Collateral sensitivity to nitrosoureas in multidrug-resistant cells selected with verapamil.

We have examined the effects of the nitrosoureas, streptozotocin (STZ) and 1,3-bis(chloroethyl)-1-nitrosourea (BCNU), on a human multiple myeloma cell line, RPMI 8226, and its drug-resistant variants. Cell lines selected for doxorubicin (DOX) resistance alone displayed a STZ and BCNU cytotoxicity profile similar to that of the parent cell line. In contrast, two of the drug-resistant variants selected with DOX plus verapamil, an agent which inhibits P-glycoprotein-mediated multidrug resistance, displayed a collateral sensitivity to STZ and BCNU. Verapamil was included in the selection protocol because it has been shown to inhibit the P-glycoprotein-mediated multidrug resistance phenotype and is now in clinical trials as a chemosensitizing agent. The collateral sensitivity to these nitrosoureas seen in the DOX plus verapamil-selected cell lines is due to the functional loss of a DNA repair molecule, O6-Methylguanine DNA methyltransferase (MGMT). The functional loss of MGMT is secondary to the loss of MGMT gene expression. The loss of MGMT gene expression is not due to loss or gross rearrangement of the MGMT-coding region. If this selection pressure applied in vitro reflects the in vivo situation, then new chemotherapeutic strategies may be devised to exploit this phenomenon. These cell lines will serve as useful models for delineating mechanisms which govern MGMT expression.