Storage Conditions and Passages Alter IL-6 Secretion in C26 Adenocarcinoma Cell Lines

The C26 adenocarcinoma tumor line is frequently used to establish peripheral tumors in mice for the study of cancer cachexia and cancer-related fatigue. Recently, we have noticed a progressive decline in the effects of tumor growth on our biological and behavioral measures in the tumor-bearing mice. Therefore, we compared effects of three aliquots of the C26 tumor cell line that differed in storage condition and number of passages on cytokine secretion, tumor growth, weight loss and fatigue behavior. Three aliquots of the C26 tumor line were selected as alpha (α), beta (β), and gamma (γ). Aliquot α was an original C26 stock line that had been stored at −80 °C. Aliquot β was stored in liquid nitrogen. Aliquot γ was taken from aliquot β and passaged three times. The three aliquots of the C26 tumor line showed differences in IL-6 mRNA and protein secretion in vitro, with aliquot β showing the greatest IL-6 secretion. These differences were mirrored in vivo. Plasma IL-6 levels were elevated in all tumor bearing mice but was greatest in group β mice. Carcass weight was decreased in all three tumor groups. Brain expression of IL-1β mRNA was greatest in group β and group β demonstrated the greatest decline in running activity at day 19. Storage conditions and number of passages influence C26 tumor cell secretion of cytokines. Variations in C26 aliquots may explain differences observed between laboratories using the same cell line. We recommend always storing cell lines in liquid nitrogen and limiting the number of passages before use in experiments

Challenges for Malaria Elimination in Zanzibar: Pyrethroid Resistance in Malaria Vectors and Poor Performance of Long-Lasting Insecticide Nets.

Long-lasting insecticide treated nets (LLINs) and indoor residual house spraying (IRS) are the main interventions for the control of malaria vectors in Zanzibar. The aim of the present study was to assess the susceptibility status of malaria vectors against the insecticides used for LLINs and IRS and to determine the durability and efficacy of LLINs on the island. Mosquitoes were sampled from Pemba and Unguja islands in 2010--2011 for use in WHO susceptibility tests. One hundred and fifty LLINs were collected from households on Unguja, their physical state was recorded and then tested for efficacy as well as total insecticide content. Species identification revealed that over 90% of the Anopheles gambiae complex was An. arabiensis with a small number of An. gambiae s.s. and An. merus being present. Susceptibility tests showed that An. arabiensis on Pemba was resistant to the pyrethroids used for LLINs and IRS. Mosquitoes from Unguja Island, however, were fully susceptible to all pyrethroids tested. A physical examination of 150 LLINs showed that two thirds were damaged after only three years in use. All used nets had a significantly lower (p < 0.001) mean permethrin concentration of 791.6 mg/m2 compared with 944.2 mg/m2 for new ones. Their efficacy decreased significantly against both susceptible An. gambiae s.s. colony mosquitoes and wild-type mosquitoes from Pemba after just six washes (p < 0.001). The sustainability of the gains achieved in malaria control in Zanzibar is seriously threatened by the resistance of malaria vectors to pyrethroids and the short-lived efficacy of LLINs. This study has revealed that even in relatively well-resourced and logistically manageable places like Zanzibar, malaria elimination is going to be difficult to achieve with the current control measures

Fluoxetine Prevents the Development of Depressive-like Behavior in a Mouse Model of Cancer Related Fatigue

Cancer patients frequently suffer from fatigue, a complex syndrome associated with tiredness and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, escalates during treatment, and can persist for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. We have previously shown that increased pro-inflammatory cytokine expression in the brain contributes to depressive- and fatigue-like behaviors in a mouse model of CRF. Inflammatory cytokines increase the activity of indoleamine 2,3-dioxygenase (IDO) and kynurenine 3-monooxygenase (KMO), which competitively reduce serotonin synthesis. Reduced serotonin availability in the brain and increased production of alternative neuroactive metabolites of tryptophan are thought to contribute to the development of depression and fatigue. The purpose of this study was to determine the effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on brain cytokines and behavioral measures of fatigue and depression in tumor-bearing mice. Here we show that tumor growth increased brain expression of pro-inflammatory cytokines and KMO. Treatment with fluoxetine had no effect on tumor growth, muscle wasting, fatigue behavior, or cytokine expression in the brain. Fluoxetine, however, reduced depressive-like behaviors in tumor bearing mice. In conclusion, our data confirm that increased brain expression of pro-inflammatory cytokines is associated with tumor-induced fatigue- and depressive-like behaviors. However, it is possible to separate the effects of tumor growth on mood and fatigue-like behaviors using SSRIs such as fluoxetine

Evaluation of bioluminescence-based assays of anti-malarial drug activity

Transgenic Plasmodium falciparum expressing luciferase offers an attractive bioluminescence-based assay platform for the investigation of the pharmacological properties of anti-malarial drugs. Here a side-by-side comparison of bioluminescence and fluorescence-based assays, utilizing a luciferase reporter cassette that confers a strong temporal pattern of luciferase expression during the S-phase of intraerythrocytic development, is reported

Ibuprofen Ameliorates Fatigue- And Depressive-Like Behavior in Tumor-Bearing Mice

Aims: Cancer-related fatigue (CRF) is often accompanied by depressed mood, both of which reduce functional status and quality of life. Research suggests that increased expression of pro-inflammatory cytokines is associated with skeletal muscle wasting and depressive- and fatigue-like behaviors in rodents and cancer patients. We have previously shown that treatment with ibuprofen, a nonsteroidal anti-inflammatory drug, preserved muscle mass in tumor-bearing mice. Therefore, the purpose of the present study was to determine the behavioral effects of ibuprofen in a mouse model of CRF. Main methods: Mice were injected with colon-26 adenocarcinoma cells and treated with ibuprofen (10 mg/kg) in the drinking water. Depressive-like behavior was determined using the forced swim test (FST). Fatigue-like behaviors were determined using voluntary wheel running activity (VWRA) and grip strength. The hippocampus, gastrocnemius muscle, and serum were collected for cytokine analysis. Key findings: Tumor-bearing mice showed depressive-like behavior in the FST, which was not observed in mice treated with ibuprofen. VWRA and grip strength declined in tumor-bearing mice, and ibuprofen attenuated this decline. Tumor-bearing mice had decreased gastrocnemius muscle mass and increased expression of IL-6, MAFBx and MuRF mRNA, biomarkers of protein degradation, in the muscle. Expression of IL-1β and IL-6 was also increased in the hippocampus. Treatment with ibuprofen improved muscle mass and reduced cytokine expression in both the muscle and hippocampus of tumor-bearing mice. Significance: Ibuprofen treatment reduced skeletal muscle wasting, inflammation in the brain, and fatigue- and depressive-like behavior in tumor-bearing mice. Therefore, ibuprofen warrants evaluation as an adjuvant treatment for CRF

Losartan Treatment Attenuates Tumor-induced Myocardial Dysfunction

Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin–angiotensin–aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT) 1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction. Methods and results: Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8 weeks of age. Simultaneously, mice were administered Losartan (10 mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19 days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice. Conclusions: These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation

Unusual placement of intrathecal baclofen pumps: report of two cases

Intrathecal baclofen delivery via implantable pump represents an important modality for symptomatic relief in patients with chronic spasticity. Pumps are routinely implanted subcutaneously in the anterior abdominal wall. We describe two unusual cases where skin-related complications necessitated revision surgery in order to relocate the pump to alternative sites. The first patient was an international power canoeist, whose strenuous exercise programme interfered with his pump’s original siting. The second patient was a cachectic university student with a history of cerebral palsy, who maintained low body mass despite attempted weight gain. The relocation of these two intrathecal devices to the medial compartment of the right thigh and right iliac fossa, respectively, is described

Confidential Boosting with Random Linear Classifiers for Outsourced User-generated Data

User-generated data is crucial to predictive modeling in many applications. With a web/mobile/wearable interface, a data owner can continuously record data generated by distributed users and build various predictive models from the data to improve their operations, services, and revenue. Due to the large size and evolving nature of users data, data owners may rely on public cloud service providers (Cloud) for storage and computation scalability. Exposing sensitive user-generated data and advanced analytic models to Cloud raises privacy concerns. We present a confidential learning framework, SecureBoost, for data owners that want to learn predictive models from aggregated user-generated data but offload the storage and computational burden to Cloud without having to worry about protecting the sensitive data. SecureBoost allows users to submit encrypted or randomly masked data to designated Cloud directly. Our framework utilizes random linear classifiers (RLCs) as the base classifiers in the boosting framework to dramatically simplify the design of the proposed confidential boosting protocols, yet still preserve the model quality. A Cryptographic Service Provider (CSP) is used to assist the Cloud's processing, reducing the complexity of the protocol constructions. We present two constructions of SecureBoost: HE+GC and SecSh+GC, using combinations of homomorphic encryption, garbled circuits, and random masking to achieve both security and efficiency. For a boosted model, Cloud learns only the RLCs and the CSP learns only the weights of the RLCs. Finally, the data owner collects the two parts to get the complete model. We conduct extensive experiments to understand the quality of the RLC-based boosting and the cost distribution of the constructions. Our results show that SecureBoost can efficiently learn high-quality boosting models from protected user-generated data

X-ray irradiation of soda-lime glasses studied in situ with surface plasmon resonance spectroscopy

We present here a study of hard X-ray irradiation of soda-lime glasses performed in situ and in real time. For this purpose, we have used a Au thin film grown on glass and studied the excitation of its surface plasmon resonance (SPR) while irradiating the sample with X-rays, using a recently developed experimental setup at a synchrotron beamline [Serrano et al., Rev. Sci. Instrum. 83, 083101 (2012)]. The extreme sensitivity of the SPR to the features of the glass substrate allows probing the modifications caused by the X-rays. Irradiation induces color centers in the soda-lime glass, modifying its refractive index. Comparison of the experimental results with simulated data shows that both, the real and the imaginary parts of the refractive index of soda-lime glasses, change upon irradiation in time intervals of a few minutes. After X- ray irradiation, the effects are partially reversible. The defects responsible for these modifications are identified as non-bridging oxygen hole centers, which fade by recombination with electrons after irradiation. The kinetics of the defect formation and fading process are also studied in real time