Trait-specific effects of exogenous triiodothyronine on cytokine and behavioral responses to simulated systemic infection in male Siberian hamsters.

Seasonal changes in day length enhance and suppress immune function in a trait-specific manner. In Siberian hamsters (Phodopus sungorus) winter-like short days (SDs) increase blood leukocyte concentrations and adaptive T cell dependent immune responses, but attenuate innate inflammatory responses to simulated infections. Thyroid hormone (TH) signaling also changes seasonally and has been implicated in modulation of the reproductive axis by day length. Immunologically, TH administration in long days (LD) enhances adaptive immune responses in male Siberian hamsters, mimicking effects of SDs. This experiment tested the hypothesis that T3 is also sufficient to mimic the effects of SD on innate immune responses. Adult male hamsters housed in LDs were pretreated with triiodothyronine (T3; 1 µg, s.c.) or saline (VEH) daily for 6 weeks; additional positive controls were housed in SD and received VEH, after which cytokine, behavioral, and physiological responses to simulated bacterial infection (lipopolysaccharide; LPS) were evaluated. SD pretreatment inhibited proinflammatory cytokine mRNA expression (i.e. interleukin 1ß, nuclear factor kappa-light-chain-enhancer of activated B cells). In addition, the magnitude and persistence of anorexic and cachectic responses to LPS were also lower in SD hamsters, and LPS-induced inhibition of nest building behavior was absent in SD. T3 treatments failed to affect behavioral (food intake, nest building) or somatic (body mass) responses to LPS in LD hamsters, but one CNS cytokine response to LPS (e.g., hypothalamic TNFα) was augmented by T3. Together these data implicate thyroid hormone signaling in select aspects of innate immune responses to seasonal changes in day length.

Natural products as modulator of autophagy with potential clinical prospects.

Natural compounds derived from living organisms are well defined for their remarkable biological and pharmacological properties likely to be translated into clinical use. Therefore, delving into the mechanisms by which natural compounds protect against diverse diseases may be of great therapeutic benefits for medical practice. Autophagy, an intricate lysosome-dependent digestion process, with implications in a wide variety of pathophysiological settings, has attracted extensive attention over the past few decades. Hitherto, accumulating evidence has revealed that a large number of natural products are involved in autophagy modulation, either inducing or inhibiting autophagy, through multiple signaling pathways and transcriptional regulators. In this review, we summarize natural compounds regulating autophagy in multifarious diseases including cancer, neurodegenerative diseases, cardiovascular diseases, metabolic diseases, and immune diseases, hoping to inspire further investigation of the underlying mechanisms of natural compounds and to facilitate their clinical use for multiple human diseases.

Thalamic lesions: a radiological review.

BACKGROUND: Thalamic lesions are seen in a multitude of disorders including vascular diseases, metabolic disorders, inflammatory diseases, trauma, tumours, and infections. In some diseases, thalamic involvement is typical and sometimes isolated, while in other diseases thalamic lesions are observed only occasionally (often in the presence of other typical extrathalamic lesions). SUMMARY: In this review, we will mainly discuss the MRI characteristics of thalamic lesions. Identification of the origin of the thalamic lesion depends on the exact localisation inside the thalamus, the presence of extrathalamic lesions, the signal changes on different MRI sequences, the evolution of the radiological abnormalities over time, the history and clinical state of the patient, and other radiological and nonradiological examinations.

[Research progresses of plant polysaccharides on cell adhesion].

Cell adhesion mediated by cell adhesion molecules (CAMs) constitutes essential life phenomenon. In inflammation, immunity, infection, thrombosis, tumor metastasis and wound healing, cell adhesion comes into being the basic physiological and pathological process. Intervening with cell adhesion has been the important therapeutic and prophylactic strategies for diseases. Accumulated evidence has indicated that plant polysaccharides especially those exacted from Chinese traditional and herbal drugs displayed various pharmacological effects such as anti-inflammation, anti-cancer, anti-infection, immunomodulation, cardiovascular protective effects and so on. In this paper, the research progress of plant polysaccharides on cell adhesion is reviewed.

Irreversible muscle damage in bodybuilding due to long-term intramuscular oil injection.

Intramuscular oil injections generating slowly degrading oil-based depots represent a controversial subject in bodybuilding and fitness. However they seem to be commonly reported in a large number of non-medical reports, movies and application protocols for 'site-injections'. Surprisingly the impact of long-term (ab)use on the musculature as well as potential side-effects compromising health and sports ability are lacking in the medical literature. We present the case of a 40 year old male semi-professional bodybuilder with systemic infection and painful reddened swellings of the right upper arm forcing him to discontinue weightlifting. Over the last 8 years he daily self-injected sterilized sesame seed oil at numerous intramuscular locations for the purpose of massive muscle building. Whole body MRI showed more than 100 intramuscular rather than subcutaneous oil cysts and loss of normal muscle anatomy. 2-step septic surgery of the right upper arm revealed pus-filled cystic scar tissue with the near-complete absence of normal muscle. MRI 1 year later revealed the absence of relevant muscle regeneration. Persistent pain and inability to perform normal weight training were evident for at least 3 years post-surgery. This alarming finding indicating irreversible muscle mutilation may hopefully discourage people interested in bodybuilding and fitness from oil-injections. The impact of such chronic tissue stress on other diseases like malignancy remains to be determined.

Histone deacetylase inhibitors impair innate immune responses to Toll-like receptor agonists and to infection.

Regulated by histone acetyltransferases and deacetylases (HDACs), histone acetylation is a key epigenetic mechanism controlling chromatin structure, DNA accessibility, and gene expression. HDAC inhibitors induce growth arrest, differentiation, and apoptosis of tumor cells and are used as anticancer agents. Here we describe the effects of HDAC inhibitors on microbial sensing by macrophages and dendritic cells in vitro and host defenses against infection in vivo. HDAC inhibitors down-regulated the expression of numerous host defense genes, including pattern recognition receptors, kinases, transcription regulators, cytokines, chemokines, growth factors, and costimulatory molecules as assessed by genome-wide microarray analyses or innate immune responses of macrophages and dendritic cells stimulated with Toll-like receptor agonists. HDAC inhibitors induced the expression of Mi-2ß and enhanced the DNA-binding activity of the Mi-2/NuRD complex that acts as a transcriptional repressor of macrophage cytokine production. In vivo, HDAC inhibitors increased the susceptibility to bacterial and fungal infections but conferred protection against toxic and septic shock. Thus, these data identify an essential role for HDAC inhibitors in the regulation of the expression of innate immune genes and host defenses against microbial pathogens.

How healthy are chronically ill patients after eight years of homeopathic treatment?--Results from a long term observational study.

BACKGROUND: Homeopathy is a highly debated but often used medical treatment. With this cohort study we aimed to evaluate health status changes under homeopathic treatment in routine care. Here we extend former results, now presenting data of an 8-year follow-up. METHODS: In a prospective, multicentre cohort study with 103 homeopathic primary care practices in Germany and Switzerland, data from all patients (age >1 year) consulting the physician for the first time were observed. The main outcome measures were: The patients' perceived change in complaint severity (numeric rating scales from 0 = no complaint to 10 = maximal severity) and quality of life as measured by the SF-36 at baseline, and after 2 and 8 years. RESULTS: A total of 3,709 patients were studied, 73% (2,722 adults, 72.8% female, age at baseline 41.0 +/- 12.3; 819 children, 48.4% female, age 6.5 +/- 4.0) contributed data to the 8-year follow-up. The most frequent diagnoses were allergic rhinitis and headache in adults, and atopic dermatitis and multiple recurrent infections in children. Disease severity decreased significantly (p < 0.001) between baseline, 2 and 8 years (adults from 6.2 +/- 1.7 to 2.9 +/- 2.2 and 2.7 +/- 2.1; children from 6.1 +/- 1.8 to 2.1 +/- 2.0 and 1.7 +/- 1.9). Physical and mental quality of life sores also increased considerably. Younger age, female gender and more severe disease at baseline were factors predictive of better therapeutic success. CONCLUSION: Patients who seek homeopathic treatment are likely to improve considerably. These effects persist for as long as 8 years.

Severe dysphagia as the presenting symptom of Wernicke-Korsakoff syndrome in a non-alcoholic man.

We present the case of a non-alcoholic man, who, following severe malnutrition, presented with dysphagia that necessitated gastrostomy tube placement. The patient subsequently developed encephalopathy, at which point thiamine deficiency was suspected and thiamine supplementation initiated. The encephalopathy and the dysphagia resolved, but the patient was left with a dense amnestic deficit consistent with Korsakoff syndrome. MRI at the time of the encephalopathy revealed lesions consistent with Wernicke-Korsakoff syndrome. This case represents a remarkable example of Wernicke-Korsakoff syndrome that for a prolonged time period had as its sole manifestation severe dysphagia. To our knowledge, there is only one similar case reported in the literature. This case serves to alert neurologists that isolated dysphagia may be the presenting symptom of this classic neurological syndrome even in the absence of alcoholism.

[Mechanisms of fever]. / Mécanismes de la fièvre.

Fever represents a normal and adaptative response developed in case of host aggression, notably by infectious agents, and is part of a large defense system, the acute phase response. Fever mediators are mainly derived from the host cells and are pyrogenous cytokines such as interleukin-1, tumour necrosis factor alpha, interleukin-6 or interferons which act at the hypothalamus level via prostaglandin E2. Although fever has been conserved through evolution, its beneficial effects in humans are not well-established.

Regulatory potential of fever-range whole body hyperthermia on Langerhans cells and lymphocytes in an antigen-dependent cellular immune response.

The febrile response is one of the most common features of infection and inflammation. However, temperature is rarely a variable in experimental immunological investigations. To determine whether the thermal microenvironment has any immunoregulatory potential in an Ag-dependent response, we applied a mild fever-range whole body hyperthermia (FR-WBH) protocol to BALB/c mice experiencing the contact hypersensitivity (CHS) reaction. We observed that the timing of this FR-WBH treatment relative to the different phases of the CHS response was crucial to the outcome. FR-WBH treatment before sensitization with a 0.5% FITC solution resulted in a depressed CHS response. This appears to be due to direct effects of FR-WBH on epidermal Langerhans cell trafficking to the draining lymph nodes. In contrast, application of FR-WBH directly after application of the elicitation dose of FITC solution resulted in an enhanced reaction. This result correlates with increased homing of lymphocytes to the site of elicitation. Overall, these data have important implications regarding the role of thermal changes experienced during infection and the clinical use of FR-WBH relative to immunotherapeutic strategies.

Skeletal evidence of health and disease in pre-contact Alaskan Eskimos and Aleuts.

There have been relatively few paleopathological studies of arctic populations to date, compared to other regions of North America. Studies aimed at elucidating patterns of health and disease in arctic peoples prior to contact and assessing inter- and intraregional differences in disease patterns have been particularly few. In the present study, five pre-contact skeletal samples (N = 193), representing 4 Eskimo populations from northern coastal Alaska and 1 Aleut population from the eastern Aleutian Islands, were examined macroscopically for the following indicators of health status: cribra orbitalia, porotic hyperostosis, trauma, infection, dental caries, abscesses, antemortem tooth loss, periodontal disease, and dental attrition. In addition, archeological and epidemiological data were used to help reconstruct the health of these populations. The goals of the analysis were 2-fold: 1) to assess the pre-contact health of North Alaskan Eskimos and Aleuts in order to provide a baseline comparison for the post-contact health of these groups, and 2) to determine if any differences in disease patterns exist between the Eskimos and Aleuts that might be related to differences in their physical environment, subsistence patterns, and cultural practices. The analysis revealed that both groups suffered from a variety of health problems prior to contact, including iron deficiency anemia, trauma, infection, and various forms of dental pathology. Statistical comparisons of the 2 groups revealed that Eskimos and Aleuts had different patterns of health and disease prior to contact. Most notably, the Aleuts had a significantly higher frequency of cranial trauma and infracranial infection than the Eskimos, while the latter had a significantly higher frequency of enamel hypoplasia. An examination of the physical and cultural environment of the 2 groups reveals several possible explanations for these differences, including warfare, subsistence pursuits, and housing practices. The documentation of these differences indicates that variability in pre-contact disease patterns can be identified between hunter-gatherer populations living in similar environments and exhibiting similar general lifestyles.

Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats.

The effect of the combination of total parenteral nutrition (TPN) and systemic sepsis on mucosal morphology and protein synthesis was investigated. Rats were given a standard TPN mixture consisting of glucose (216 kcal.kg-1.day-1), lipid (24 kcal.kg-1.day-1), and amino acids (1.5 g N.kg-1.day-1) for 5 days. On the 5th day the rats (n = 37) were randomized into four groups according to diet as follows: 1) control nonseptic on standard TPN, 2) control nonseptic on TPN with glutamine, 3) septic on standard TPN, and 4) septic with the TPN supplemented with glutamine. Twenty hours after the injection of Escherichia coli, the rats were given a 4-h constant infusion of [U-14C]leucine to determine the mucosal fractional protein synthesis rates. The following results were obtained. 1) Histological examination showed that systemic sepsis caused tissue damage to the ileum and jejunum. 2) Glutamine supplementation attenuated these changes. 3) There were no visible changes to the colon either from glutamine supplementation or sepsis. 4) Sepsis was associated with an increase in mucosal protein synthesis and decreased muscle synthesis. 5) Addition of glutamine to the TPN mix further increased protein synthesis in the intestinal mucosa of septic rats.

Effects of epidermal growth factor and glutamine-supplemented parenteral nutrition on the small bowel of septic rats.

1. The effects of parenteral nutrition with or without glutamine supplementation and epidermal growth factor treatment (0.15 microgram/g body weight) was studied in the small bowel of septic rats after 4 days. 2. Septic rats infused with glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment survived sepsis significantly better than other septic rats given parenteral nutrition. The cumulative percentage of deaths over 4 days in septic rats infused with glutamine-supplemented parenteral nutrition was 20% (without epidermal growth factor) and 15% (with epidermal growth factor) compared with 50% in septic rats treated with parenteral nutrition without glutamine and 35% in septic rats given parenteral nutrition without glutamine but with epidermal growth factor treatment. 3. Glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment resulted in improved nitrogen balance in septic rats. The cumulative nitrogen balance over the 4 day period was the least negative as compared with other groups of septic rats. 4. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited marked increases in intestinal net rates of utilization of glutamine (P less than 0.001) and production of ammonia (P less than 0.001) compared with septic rats given parenteral nutrition without glutamine and/or epidermal growth factor treatment. 5. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited significant increases in jejunal wet weight (by 32.4-40.6%), DNA content (by 24.2-34.7%), protein content (by 29.1-50.0%), villus height (by 16.3-26.4%) and crypt depth (by 20.3-29.6%) compared with other groups of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Synovial pseudarthrosis: a clinical, roentgenographic-scintigraphic, and pathologic study.

Seventy-six patients with synovial pseudarthrosis were reviewed. This is a distinct pathologic entity which is a different form of nonunion. The humerus, femur, and tibia were the bones most commonly involved. Routine roentgenograms were not beneficial but 99mTc scans were useful for identifying this entity in 93% of cases. Light and electron microscopy revealed normal synovial lining tissue. Motion and infection may lead to the development of this condition. The results of treatment were a 43% success rate in infected cases and 59% for noninfected cases, which is far different from that of regular nonunion.