Dose Range-Finding Toxicity Study in Rats With Recombinant Human Lactoferrin Produced in Komagataella phaffii.

The oral toxicity of recombinant human lactoferrin (rhLF, Helaina rhLF, Effera™) produced in Komagataella phaffii was investigated in adult Sprague Dawley rats by once daily oral gavage for 14 consecutive days. The study used groups of 3-6 rats/sex/dose. The vehicle control group received sodium citrate buffer, and the test groups received daily doses of 200, 1000, and 2000 mg of rhLF in sodium citrate buffer per kg body weight. Bovine LF at 2000 mg/kg body weight per day was used as a comparative control. Clinical observations, body weight, hematology, clinical chemistry, iron parameters, immunophenotyping, and gross examination at necropsy were used as criteria for detecting the effects of treatment in all groups and to help select dose levels for future toxicology studies. Quantitative LF levels were also analyzed as an indication of bioavailability. Overall, administration of Helaina rhLF by once daily oral gavage for 14 days was well tolerated in rats at levels up to 2000 mg/kg/day, or 57 × Helaina's intended commercial use in adults, and indicating that a high dose of 2000 mg/kg/day is appropriate for future definitive toxicology studies.

Characterization of Adult Canine Kidney Epithelial Stem Cells That Give Rise to Dome-Forming Tubular Cells.

Dome formation can occur in cultured tubular epithelial cells originating from various tissues, including the mammary gland and the kidney. The isolation and characterization of normal kidney epithelial stem cells that give rise to dome-forming tubular cells have never been reported. We attempted to isolate and characterize canine kidney epithelial stem cells using a simple cell culture method that we have previously used to isolate other adult human stem cells. Dome-forming kidney epithelial cells were derived from dissociated adult canine kidney tissues that were cultured in a modified keratinocyte serum-free medium supplemented with N-acetyl-l-cysteine, l-ascorbic acid 2-phosphate, nicotinamide, and fetal bovine serum. These cells exhibited high self-renewal capacity in long-term culture (growth for >13 months and 30 cumulative population doublings) and exhibited characteristics of stem cells, including (1) deficiency in gap junctional intercellular communication, (2) anchorage-independent growth, (3) expression of stem cell markers octamer-binding transcription factor 4 and SRY (sex determining region Y)-box 2, (4) expression of cell surface markers CD24 and CD133, and (5) multipotent differentiation into osteoblasts, adipocytes, chondrocytes, and dome-forming tubular cells. Most of these characteristics are shared by the well-known canine renal tubule-derived immortalized Madin-Darby Canine Kidney cell line. Furthermore, the putative canine kidney stem cells developed in this study formed budding tubule-like organoids on Matrigel and required high cell density (>4,000 cells/cm2) for sustained growth and confluency for dome formation. The signal transducer and activator of transcription-3 (STAT3) phosphorylation inhibitor, AG490, inhibited colony-forming efficiency and dome formation, whereas lipopolysaccharide, an activator of STAT3, increased colony-forming efficiency in a dose-dependent manner. These results are consistent with the hypothesis that high cell density induces STAT3 expression, which promotes both stem cell self-renewal and differentiation into tubular cells. Our novel cell culture method should be useful for the future development of normal human kidney stem cells for clinical applications and for studying mechanisms of nephrotoxicity.

Salutarismo e medicalização da vida cotidiana / Healthism and the medicalization of everyday life / Salutarismo y la medicalización de la vida cotidiana

Este artigo trata de algumas implicações da nova consciência de saúde e seus movimentos ­ de saúde holística e autocuidado ­ para a definição e solução de problemas relacionados à 'saúde'. O salutarismo representa um modo particular de considerar o problema da saúde e é característico desse novo tipo de consciência e de seus movimentos. Ele pode ser melhor entendido como uma forma de medicalização, no sentido de que ainda retém noções-chave da medicina. Assim como a medicina, o salutarismo situa o problema da saúde e da doença no nível do indivíduo, e as soluções são elaboradas no plano individual. Na medida em que o salutarismo dá contornos a crenças populares, continuaremos a ter uma concepção e estratégias de promoção de saúde apolíticas, e, portanto, sem efeitos. Além disso, ao conceder à saúde um estatuto de supervalor, uma metáfora para tudo o que há de bom na vida, o salutarismo reforça a privatização da luta por generalização do bem-estar.

This article considers some implications of the new health consciousness and movements ­ holistic health and self-care ­ for the definition of and solution to problems related to 'health'. Healthism represents a particular way of viewing the health problem, and is characteristic of the new health consciousness and movements. It can best be understood as a form of medicalization, meaning that it still retains key medical notions. Like medicine, healthism situates the problem of health and disease at the level of the individual. Solutions are formulated at that level as well. To the extent that healthism shapes popular beliefs, we will continue to have a non-political, and therefore, ultimately ineffective conception and strategy of health promotion. Further, by elevating health to a super value, a metaphor for all that is good in life, healthism reinforces the privatization of the struggle for generalized well-being.

Este artículo considera algunas implicaciones de la nueva conciencia de salud y movilización ­ salud holística y autocuidado ­ para la definición y solución de problemas relacionados con la 'salud'. El estilo de vida representa una forma particular de problema de salud, y es característico de la nueva conciencia de la salud y los movimientos. Puede entenderse mejor como una forma de medicalización, lo que significa que todavía conserva nociones médicas clave. Al igual que la medicina, la salud sitúa el problema de la enfermedad en el nivel del individuo. Las soluciones se formulan a ese nivel también. En la medida en que el sistema de salud moldee las creencias populares, seguiremos teniendo una no política, y por lo tanto, en última instancia ineficaz concepción y estrategia de promoción de la salud. Además, elevando la salud a un supervalor, una metáfora de todo eso es bueno en la vida, el saneamiento refuerza la privatización de la lucha por la generalización del bienestar.

Potential Role of Curcumin Against Biofilm-Producing Organisms on the Skin: A Review.

Turmeric root (Curcuma longa) is predominantly used as a spice, but has also long been known to possess antimicrobial, analgesic, antiinflammatory, and anticancer properties. One predominant group of active compounds in turmeric are curcuminoids, namely bright yellow-pigmented curcumin. While modern science has yet to fully investigate the therapeutic claims of turmeric and its derivatives, results have proven promising in decreasing pain and inflammation in arthritis, improving insulin sensitivity in diabetes, and even curing a variety of infections. The purpose of this review is to discuss the potential for curcumin as an agent against microbial infections, with a special focus on the skin and in the development of bacterial biofilms. Curcumin has demonstrated bactericidal efficacy against a variety of infections when administered with antibiotics in several clinical studies, with consistent antimicrobial activity demonstrated in vitro, as well as in urinary tract infections, gingival infections, and chronic wound infections. Hypothesized mechanisms of action include curcumin's ability to perturb bacterial membranes, disturb protofillament assembly, and even impair bacterial virulence factors. Further investigation is needed to fully understand which organisms are most susceptible to the effects of curcumin and how curcumin can be implemented in dermatology to treat skin conditions such as chronic wounds and acne vulgaris. Copyright © 2017 John Wiley & Sons, Ltd.

TCDD administered on activated carbon eliminates bioavailability and subsequent shifts to a key murine gut commensal.

Activated carbon (AC) is an increasingly attractive remediation alternative for the sequestration of dioxins at contaminated sites globally. However, the potential for AC to reduce the bioavailability of dioxins in mammals and the residing gut microbiota has received less attention. This question was partially answered in a recent study examining 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hallmark toxic responses in mice administered with TCDD sequestered by AC or freely available in corn oil by oral gavage. Results from that study support the use of AC to significantly reduce the bioavailability of TCDD to the host. Herein, we examined the bioavailability of TCDD sequestered to AC on a key murine gut commensal and the influence of AC on the community structure of the gut microbiota. The analysis included qPCR to quantify the expression of segmented filamentous bacteria (SFB) in the mouse ileum, which has responded to TCDD-induced host toxicity in previous studies and community structure via sequencing the 16S ribosomal RNA (rRNA) gene. The expression of SFB 16S rRNA gene and functional genes significantly increased with TCDD administered with corn oil vehicle. Such a response was absent when TCDD was sequestered by AC. In addition, AC appeared to have a minimal influence on murine gut community structure and diversity, affecting only the relative abundance of Lactobacillaceae and two other groups. Results of this study further support the remedial use of AC for eliminating bioavailability of TCDD to host and subsequent influence on the gut microbiome.

Sequestration of 2,3,7,8-tetrachlorodibenzo-p-dioxin by activated carbon eliminates bioavailability and the suppression of immune function in mice.

The effectiveness of activated carbon in reducing the bioavailability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was examined from the context of using in situ sorbent amendments to remediate soils/sediments contaminated with polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs). This technology has gained rapid acceptance based on observations that activated carbon amendments predictably lower PCDD/F concentrations in water and bioaccumulation by simple aquatic organisms and earthworms; it has been assumed that bioavailability to mammals is similarly reduced, although this has been disproven for other sorbent materials. In the present study TCDD was absorbed to a microporous activated carbon (TCDD-AC) using the incipient wetness method. An aqueous suspension of TCDD-AC and an equivalent dosage of TCDD in corn oil were administered by oral gavage to B6C3F1 mice. The relative bioavailability of TCDD-AC was determined by quantifying and comparing the hepatic induction of cyp1A1 (messenger ribonucleic acid) and suppression of the immunoglobulin M antibody-forming cell immune response by the 2 forms of TCDD. A concentration-dependent response was observed for both assays when TCDD in corn oil was administered to mice. However, when equivalent masses of TCDD were administered as TCDD-AC, no induction of cyp1A1 or suppression of the immunoglobulin M antibody-forming cell response was observed. The absence of these 2 sensitive aryl hydrocarbon receptor-mediated responses in mice provides the first direct evidence that activated carbon can sequester TCDD in a form that eliminates its bioavailability to mammals. These results support the premise that activated carbon can be used to reduce the bioeffective dose of TCDD delivered to mammals and that activated carbon amendments may provide a low-cost alternative to traditional remediation technologies. Environ Toxicol Chem 2017;36:2671-2678. © 2017 SETAC.

Diagnosis and treatment of plantar fasciitis.

Plantar fasciitis, a self-limiting condition, is a common cause of heel pain in adults. It affects more than 1 million persons per year, and two-thirds of patients with plantar fasciitis will seek care from their family physician. Plantar fasciitis affects sedentary and athletic populations. Obesity, excessive foot pronation, excessive running, and prolonged standing are risk factors for developing plantar fasciitis. Diagnosis is primarily based on history and physical examination. Patients may present with heel pain with their first steps in the morning or after prolonged sitting, and sharp pain with palpation of the medial plantar calcaneal region. Discomfort in the proximal plantar fascia can be elicited by passive ankle/first toe dorsiflexion. Diagnostic imaging is rarely needed for the initial diagnosis of plantar fasciitis. Use of ultrasonography and magnetic resonance imaging is reserved for recalcitrant cases or to rule out other heel pathology; findings of increased plantar fascia thickness and abnormal tissue signal the diagnosis of plantar fasciitis. Conservative treatments help with the disabling pain. Initially, patient-directed treatments consisting of rest, activity modification, ice massage, oral analgesics, and stretching techniques can be tried for several weeks. If heel pain persists, then physician-prescribed treatments such as physical therapy modalities, foot orthotics, night splinting, and corticosteroid injections should be considered. Ninety percent of patients will improve with these conservative techniques. Patients with chronic recalcitrant plantar fasciitis lasting six months or longer can consider extracorporeal shock wave therapy or plantar fasciotomy.

Infected compartment syndrome after acupuncture.

We present a case of septicaemia and compartment syndrome of the leg in a diabetic patient, following acupuncture to his calf. An emergency decompression fasciotomy was performed on the patient and gram-positive cocci were grown from the posterior compartment wound swab cultures and group A streptococcus from his blood cultures. He remained in the Intensive Therapy Unit postoperatively, requiring inotropic support and intravenous antibiotics for his septicaemia. We would like to remind acupuncturists, to consider the possibility of heightened risks in immunocompromised patients.

Issues in the governance of Canadian hospitals, Part II: Hospital planning.

A hospital's board is directly accountable to the corporation of the hospital. Together they are accountable to the patients and communities served by the hospital, to the provincial government that funds the hospital on behalf of these patients and communities, and to the staff of the hospital. Thus, the board of trustees has a critical role in defining the purposes, principles and objectives of hospitals.

Issues in the governance of Canadian hospitals, Part 1: Structure and process.

Boards that develop robust structures and processes for governing their hospitals lay the foundation for: Long-range success. Responsible fiscal stewardship. Provision of a high quality of care. Effective governance will facilitate and enhance a board's advocacy for the hospital. In upcoming articles, we will examine these three remaining elements of effective governance in greater detail.