Treatment of cyclic vomiting syndrome with co-enzyme Q10 and amitriptyline, a retrospective study

<p>Abstract</p> <p>Background</p> <p>Cyclic vomiting syndrome (CVS), which is defined by recurrent stereotypical episodes of nausea and vomiting, is a relatively-common disabling condition that is associated with migraine headache and mitochondrial dysfunction. Co-enzyme Q10 (Co-Q) is a nutritional supplement that has demonstrated efficacy in pediatric and adult migraine. It is increasingly used in CVS despite the complete lack of studies to demonstrate its value in treatment</p> <p>Methods</p> <p>Using an Internet-based survey filled out by subjects with CVS or their parents, the efficacy, tolerability and subject satisfaction in CVS prophylaxis were queried. Subjects taking Co-Q (22 subjects) were compared against those taking amitriptyline (162 subjects), which is the general standard-of-care.</p> <p>Results</p> <p>Subjects/parents reported similar levels of efficacy for a variety of episode parameters (frequency, duration, number of emesis, nausea severity). There was a 50% reduction in at least one of those four parameters in 72% of subjects treated with amitriptyline and 68% of subjects treated Co-Q. However, while no side effects were reported on Co-Q, 50% of subjects on amitriptyline reported side effects (P = 5 × 10^-7), resulting in 21% discontinuing treatment (P = 0.007). Subjects/parents considered the benefits to outweigh the risks of treatment in 47% of cases on amitriptyline and 77% of cases on Co-Q (P = 0.008).</p> <p>Conclusion</p> <p>Our data suggest that the natural food supplement Co-Q is potentially efficacious and tolerable in the treatment of CVS, and should be considered as an option in CVS prophylaxis. Our data would likely be helpful in the design of a double-blind clinical trial.</p

Early Metabolic Flare in Squamous Cell Carcinoma after Chemotherapy is a Marker of Treatment Sensitivity In Vitro

PURPOSE: Early metabolic response with a decrease in glucose demand after cytotoxic treatment has been reported to precede tumor volume shrinkage. However, preclinical studies report of a very early rise in metabolism, a flare, following treatment. To elucidate these observations, we performed an experimental study on early metabolic response with sequential analysis of metabolic changes. METHODS: Three squamous cell carcinoma cell lines and one nontumorigenic cell line were exposed to cisplatin. The uptake of the fluorescent glucose analogue 2-NBDG was examined at days 1-6 using fluorescence microscopy. The relation between 2-NBDG-uptake and cell survival was evaluated. RESULTS: The tumor cells exhibited a high uptake of 2-NBDG, whereas the uptake in the nonmalignant cells was low. The more cisplatin sensitive cell lines exhibited a more pronounced metabolic flare than the less sensitive cell line. CONCLUSION: A metabolic flare was a very early sign of treatment response and potentially it could be used as an early marker of treatment sensitivity

Directed cell migration in the presence of obstacles

BACKGROUND: Chemotactic movement is a common feature of many cells and microscopic organisms. In vivo, chemotactic cells have to follow a chemotactic gradient and simultaneously avoid the numerous obstacles present in their migratory path towards the chemotactic source. It is not clear how cells detect and avoid obstacles, in particular whether they need a specialized biological mechanism to do so. RESULTS: We propose that cells can sense the presence of obstacles and avoid them because obstacles interfere with the chemical field. We build a model to test this hypothesis and find that this naturally enables efficient at-a-distance sensing to be achieved with no need for a specific and active obstacle-sensing mechanism. We find that (i) the efficiency of obstacle avoidance depends strongly on whether the chemotactic chemical reacts or remains unabsorbed at the obstacle surface. In particular, it is found that chemotactic cells generally avoid absorbing barriers much more easily than non-absorbing ones. (ii) The typically low noise in a cell's motion hinders the ability to avoid obstacles. We also derive an expression estimating the typical distance traveled by chemotactic cells in a 3D random distribution of obstacles before capture; this is a measure of the distance over which chemotaxis is viable as a means of directing cells from one point to another in vivo. CONCLUSION: Chemotactic cells, in many cases, can avoid obstacles by simply following the spatially perturbed chemical gradients around obstacles. It is thus unlikely that they have developed specialized mechanisms to cope with environments having low to moderate concentrations of obstacles

Work and Health, a Blind Spot in Curative Healthcare? A Pilot Study

Introduction Most workers with musculoskeletal disorders on sick leave often consult with regular health care before entering a specific work rehabilitation program. However, it remains unclear to what extent regular healthcare contributes to the timely return to work (RTW). Moreover, several studies have indicated that it might postpone RTW. There is a need to establish the influence of regular healthcare on RTW as outcome; “Does visiting a regular healthcare provider influence the duration of sickness absence and recurrent sick leave due to musculoskeletal disorders?”. Methods A cohort of workers on sick leave for 2–6 weeks due to a-specific musculoskeletal disorders was followed for 12 months. The main outcomes for the present analysis were: duration of sickness absence till 100% return to work and recurrent sick leave after initial RTW. Cox regression analyses were conducted with visiting a general health practitioner, physical therapist, or medical specialist during the sick leave period as independent variables. Each regression model was adjusted for variables known to influence health care utilization like age, sex, diagnostic group, pain intensity, functional disability, general health perception, severity of complaints, job control, and physical load at work. Results Patients visiting a medical specialist reported higher pain intensity and more functional limitations and also had a worse health perception at start of the sick leave period compared with those not visiting a specialist. Visiting a medical specialist delayed return to work significantly (HR = 2.10; 95%CI 1.43–3.07). After approximately 8 weeks on sick leave workers visiting a physical therapist returned to work faster than other workers. A recurrent episode of sick leave during the follow up quick was initiated by higher pain intensity and more functional limitations at the moment of fully return to work. Visiting a primary healthcare provider during the sickness absence period did not influence the occurrence of a new sick leave period. Conclusion Despite the adjustment for severity of the musculoskeletal disorder, visiting a medical specialist was associated with a delayed full return to work. More attention to the factor ‘labor’ in the regular healthcare is warranted, especially for those patients experiencing substantial functional limitations due to musculoskeletal disorders

Effects of a single administration of prostaglandin F2alpha, or a combination of prostaglandin F2alpha and prostaglandin E2, or placebo on fertility variables in dairy cows 3–5 weeks post partum, a randomized, double-blind clinical trial

BACKGROUND: Delayed uterine involution has negative effects on the fertility of cows; use of prostaglandin F2alpha alone as a single treatment has not been shown to consistently improve fertility. Combined administration of PGF2alpha and PGE2 increased uterine pressure in healthy cows. We hypothesized, that the combination of both prostaglandins would accelerate uterine involution and have, therefore, a positive effect on fertility variables. In commercial dairy farming, the benefit of a single post partum combined prostaglandin treatment should be demonstrated. METHODS: 383 cows from commercial dairy farms were included in this study. Uterine size and secretion were evaluated at treatment 21–35 days post partum and 14 days later. Cows were randomly allocated to one of three treatment groups: PGF2alpha and PGE2, PGF2alpha or placebo. For every animal participating in the study, the following reproduction variables were recorded: Interval from calving to first insemination, days open, number of artificial inseminations (AI) to conception; subsequent treatment of uterus, subsequent treatment of ovaries. Plasma progesterone level at time of treatment was used as a covariable. For continuous measurements, analysis of variance was performed. Fisher's exact test for categorical non-ordered data and exact Kruskal-Wallis test for ordered data were used; pairwise group comparisons with Bonferroni adjustment of significance level were performed. RESULTS: There was no significant difference among treatment groups in uterine size. Furthermore, there was no significant difference among treatments concerning days open, number of AI, and subsequent treatment of uterus and ovaries. Days from calving to first insemination tended to be shorter for cows with low progesterone level given PGF2alpha and PGE2 in combination than for the placebo-group (P = 0.024). CONCLUSION: The results of this study indicate that the administration of PGF2alpha or a combination of PGF2alpha and PGE2 21 to 35 days post partum had no beneficial effect upon measured fertility variables. The exception was a tendency for a shorter interval from calving to first insemination after administration of the combination of PGF2alpha and PGE2, as compared to the placebo group. Further research should be done in herds with reduced fertility and/or an increased incidence of postpartum vaginal discharge

Happy Aged People Are All Alike, While Every Unhappy Aged Person Is Unhappy in Its Own Way

Aging of the world's population represents one of the most remarkable success stories of medicine and of humankind, but it is also a source of various challenges. The aim of the collaborative cross-cultural European study of adult well being (ESAW) is to frame the concept of aging successfully within a causal model that embraces physical health and functional status, cognitive efficacy, material security, social support resources, and life activity. Within the framework of this project, we show here that the degree of heterogeneity among people who view aging in a positive light is significantly lower than the degree of heterogeneity of those who hold a negative perception of aging. We base this conclusion on our analysis of a survey involving 12,478 people aged 50 to 90 from six West European countries. We treat the survey database as a bipartite network in which individual respondents are linked to the actual answers they provide. Taking this perspective allows us to construct a projected network of respondents in which each link indicates a statistically validated similarity of answers profile between the connected respondents, and to identify clusters of individuals independently of demographics. We show that mental and physical well-being are key factors determining a positive perception of aging. We further observe that psychological aspects, like self-esteem and resilience, and the nationality of respondents are relevant aspects to discriminate among participants who indicate positive perception of aging

Phosphorus–iron interaction in sediments : can an electrode minimize phosphorus release from sediments?

All restoration strategies to mitigate eutrophication depend on the success of phosphorus (P) removal from the water body. Therefore, the inputs from the watershed and from the enriched sediments, that were the sink of most P that has been discharged in the water body, should be controlled. In sediments, iron (hydr)oxides minerals are potent repositories of P and the release of P into the water column may occur upon dissolution of the iron (hydr)oxides mediated by iron reducing bacteria. Several species of these bacteria are also known as electroactive microorganisms and have been recently identified in lake sediments. This capacity of bacteria to transfer electrons to electrodes, producing electricity from the oxidation of organic matter, might play a role on P release in sediments. In the present work it is discussed the relationship between phosphorus and iron cycling as well as the application of an electrode to work as external electron acceptor in sediments, in order to prevent metal bound P dissolution under anoxic conditions.The authors are grateful to two anonymous reviewers of a previous version of the manuscript for the constructive comments and suggestions. The authors also acknowledge the Grant SFRH/BPD/80528/2011 from the Foundation for Science and Technology, Portugal, awarded to Gilberto Martins

Analysis of Interactions of Salmonella Type Three Secretion Mutants with 3-D Intestinal Epithelial Cells

The prevailing paradigm of Salmonella enteropathogenesis based on monolayers asserts that Salmonella pathogenicity island-1 Type Three Secretion System (SPI-1 T3SS) is required for bacterial invasion into intestinal epithelium. However, little is known about the role of SPI-1 in mediating gastrointestinal disease in humans. Recently, SPI-1 deficient nontyphoidal Salmonella strains were isolated from infected humans and animals, indicating that SPI-1 is not required to cause enteropathogenesis and demonstrating the need for more in vivo-like models. Here, we utilized a previously characterized 3-D organotypic model of human intestinal epithelium to elucidate the role of all characterized Salmonella enterica T3SSs. Similar to in vivo reports, the Salmonella SPI-1 T3SS was not required to invade 3-D intestinal cells. Additionally, Salmonella strains carrying single (SPI-1 or SPI-2), double (SPI-1/2) and complete T3SS knockout (SPI-1/SPI-2: flhDC) also invaded 3-D intestinal cells to wildtype levels. Invasion of wildtype and TTSS mutants was a Salmonella active process, whereas non-invasive bacterial strains, bacterial size beads, and heat-killed Salmonella did not invade 3-D cells. Wildtype and T3SS mutants did not preferentially target different cell types identified within the 3-D intestinal aggregates, including M-cells/M-like cells, enterocytes, or Paneth cells. Moreover, each T3SS was necessary for substantial intracellular bacterial replication within 3-D cells. Collectively, these results indicate that T3SSs are dispensable for Salmonella invasion into highly differentiated 3-D models of human intestinal epithelial cells, but are required for intracellular bacterial growth, paralleling in vivo infection observations and demonstrating the utility of these models in predicting in vivo-like pathogenic mechanisms

A Salmonella Small Non-Coding RNA Facilitates Bacterial Invasion and Intracellular Replication by Modulating the Expression of Virulence Factors

Small non-coding RNAs (sRNAs) that act as regulators of gene expression have been identified in all kingdoms of life, including microRNA (miRNA) and small interfering RNA (siRNA) in eukaryotic cells. Numerous sRNAs identified in Salmonella are encoded by genes located at Salmonella pathogenicity islands (SPIs) that are commonly found in pathogenic strains. Whether these sRNAs are important for Salmonella pathogenesis and virulence in animals has not been reported. In this study, we provide the first direct evidence that a pathogenicity island-encoded sRNA, IsrM, is important for Salmonella invasion of epithelial cells, intracellular replication inside macrophages, and virulence and colonization in mice. IsrM RNA is expressed in vitro under conditions resembling those during infection in the gastrointestinal tract. Furthermore, IsrM is found to be differentially expressed in vivo, with higher expression in the ileum than in the spleen. IsrM targets the mRNAs coding for SopA, a SPI-1 effector, and HilE, a global regulator of the expression of SPI-1 proteins, which are major virulence factors essential for bacterial invasion. Mutations in IsrM result in disregulation of expression of HilE and SopA, as well as other SPI-1 genes whose expression is regulated by HilE. Salmonella with deletion of isrM is defective in bacteria invasion of epithelial cells and intracellular replication/survival in macrophages. Moreover, Salmonella with mutations in isrM is attenuated in killing animals and defective in growth in the ileum and spleen in mice. Our study has shown that IsrM sRNA functions as a pathogenicity island-encoded sRNA directly involved in Salmonella pathogenesis in animals. Our results also suggest that sRNAs may represent a distinct class of virulence factors that are important for bacterial infection in vivo