Influence of comorbidity with depression on interdisciplinary therapy: outcomes in patients with chronic low back pain

Introduction  

Our previous work showed higher tumour necrosis factor (TNF)-α levels in patients with chronic low back pain (cLBP) compared to healthy controls. However, patients with depression as a comorbidity did not have higher TNF-α levels in comparison to patients without depression. In this study we investigated the influence of depression on therapy outcomes such as TNF-α serum levels, pain intensity and back function in patients with cLBP. Our hypothesis was that patients with both cLBP and depression benefit no less than patients with cLBP alone from the multidisciplinary pain therapy.     

Psychological stress contributed to the development of low-grade fever in a patient with chronic fatigue syndrome: a case report

Background

Low-grade fever is a common symptom in patients with chronic fatigue syndrome (CFS), but the mechanisms responsible for its development are poorly understood. We submit this case report that suggests that psychological stress contributes to low-grade fever in CFS.

Case presentation

A 26-year-old female nurse with CFS was admitted to our hospital. She had been recording her axillary temperature regularly and found that it was especially high when she felt stress at work. To assess how psychological stress affects temperature and to investigate the possible mechanisms for this hyperthermia, we conducted a 60-minute stress interview and observed the changes in the following parameters: axillary temperature, fingertip temperature, systolic blood pressure, diastolic blood pressure, heart rate, plasma catecholamine levels, and serum levels of interleukin (IL)-1β and IL-6 (pyretic cytokines), tumor necrosis factor-α and IL-10 (antipyretic cytokines). The stress interview consisted of recalling and talking about stressful events. Her axillary temperature at baseline was 37.2°C, increasing to 38.2°C by the end of the interview. In contrast, her fingertip temperature decreased during the interview. Her heart rate, systolic and diastolic blood pressures, and plasma levels of noradrenaline and adrenaline increased during the interview; there were no significant changes in either pyretic or antipyretic cytokines during or after the interview.

Conclusions

A stress interview induced a 1.0°C increase in axillary temperature in a CFS patient. Negative emotion-associated sympathetic activation, rather than pyretic cytokine production, contributed to the increase in temperature induced by the stress interview. This suggests that psychological stress may contribute to the development or the exacerbation of low-grade fever in some CFS patients.

     

Analysis of 16S rRNA gene sequences and circulating cell-free DNA from plasma of chronic fatigue syndrome and non-fatigued subjects

Background  

The association of an infectious agent with chronic fatigue syndrome (CFS) has been difficult and is further complicated by the lack of a known lesion or diseased tissue. Cell-free plasma DNA could serve as a sentinel of infection and disease occurring throughout the body. This type of systemic sample coupled with broad-range amplification of bacterial sequences was used to determine whether a bacterial pathogen was associated with CFS. Plasma DNA from 34 CFS and 55 non-fatigued subjects was assessed to determine plasma DNA concentration and the presence of bacterial 16S ribosomal DNA (rDNA) sequences.     

Safety of TNF-blocking agents in rheumatic patients with serology suggesting past hepatitis B state: results from a cohort of 21 patients

Introduction  

Reactivation of hepatitis B virus (HBV) infection in patients with past infection has been described in 5% to 10% of individuals undergoing immunosuppressive therapies. No data are available to date on the outcome of patients treated by tumour necrosis factor-alpha (TNFα) inhibitors for chronic arthritis with a serological pattern of past HBV infection. The aim of our study was to monitor HBV markers in HBV surface antigen (HBsAg)-negative/anti-HBcAb-positive patients treated with a TNFα inhibitor for inflammatory arthritides.     

Melanocortin peptides inhibit urate crystal-induced activation of phagocytic cells

Introduction  

The melanocortin peptides have marked anti-inflammatory potential, primarily through inhibition of proinflammatory cytokine production and action on phagocytic cell functions. Gout is an acute form of arthritis caused by the deposition of urate crystals, in which phagocytic cells and cytokines play a major pathogenic role. We examined whether alpha-melanocyte-stimulating hormone (α-MSH) and its synthetic derivative (CKPV)₂ influence urate crystal-induced monocyte (Mo) activation and neutrophil responses in vitro.     

Neuropeptide Y and α-MSH Circadian Levels in Two Populations with Low Body Weight: Anorexia Nervosa and Constitutional Thinness

Context

Anorexia nervosa (AN) presents an adaptive appetite regulating profile including high levels of ghrelin and 26RFa (orexigenic) and low levels of leptin and PYY (anorexigenic). However, this adaptive mechanism is not effective in promoting food intake. The NPY/proopiomelanocortin (POMC) system plays a crucial role in the regulation of feeding behavior as NPY is the most potent orexigenic neuropeptide identified so far and as the POMC-derived peptide α-MSH drastically reduces food intake, and this peptidergic system has not been thoroughly studied in AN.

Objective

The aim of the present study was thus to investigate whether a dysfunction of the NPY/POMC occurs in two populations with low body weight, AN and constitutional thinness (CT).

Design and Settings

This was a cross-sectional study performed in an endocrinological unit and in an academic laboratory.

Investigated Subjects

Three groups of age-matched young women were studied: 23 with AN (AN), 22 CT and 14 normal weight controls.

Main Outcome Measures

Twelve-point circadian profiles of plasma NPY and α-MSH levels were measured in the three groups of investigated subjects.

Results

No significant circadian variation of NPY was detected between the three groups. Plasma α-MSH levels were significantly lower in AN (vs controls) all over the day. The CT group, compared to controls, presented lower levels of α-MSH in the morning and the evening, and an important rise during lunchtime.

Conclusion

In AN patients, the NPY system is not up-regulated under chronic undernutrition suggesting that this may play a role in the inability of anorectic women to adapt food intake to their energy demand. In contrast, low circadian α-MSH levels integrate the adaptive profile of appetite regulation of this disease. Finally, in CT women, the important α-MSH peak detected during lunchtime could explain why these patients are rapidly food satisfied.     

Perception versus polysomnographic assessment of sleep in CFS and non-fatigued control subjects: results from a population-based study

Background  

Complaints of unrefreshing sleep are a prominent component of chronic fatigue syndrome (CFS); yet, polysomnographic studies have not consistently documented sleep abnormalities in CFS patients. We conducted this study to determine whether alterations in objective sleep characteristics are associated with subjective measures of poor sleep quality in persons with CFS.     

EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients-A case control study

Background  

Previous studies suggest central nervous system involvement in chronic fatigue syndrome (CFS), yet there are no established diagnostic criteria. CFS may be difficult to differentiate from clinical depression. The study's objective was to determine if spectral coherence, a computational derivative of spectral analysis of the electroencephalogram (EEG), could distinguish patients with CFS from healthy control subjects and not erroneously classify depressed patients as having CFS.     

Expression of human α<Subscript>1</Subscript>-proteinase inhibitor in <Emphasis Type="Italic">Aspergillus niger</Emphasis>

Background  

Human α₁-proteinase inhibitor (α₁-PI), also known as antitrypsin, is the most abundant serine protease inhibitor (serpin) in plasma. Its deficiency is associated with development of progressive, ultimately fatal emphysema. Currently in the United States, α₁-PI is available for replacement therapy as an FDA licensed plasma-derived (pd) product. However, the plasma source itself is limited; moreover, even with efficient viral inactivation steps used in manufacture of plasma products, the risk of contamination from emerging viruses may still exist. Therefore, recombinant α₁-PI (r-α₁-PI) could provide an attractive alternative. Although r-α₁-PI has been produced in several hosts, protein stability in vitro and rapid clearance from the circulation have been major issues, primarily due to absent or altered glycosylation.     

Egr-1 inhibits the expression of extracellular matrix genes in chondrocytes by TNFα-induced MEK/ERK signalling

Introduction  

TNFα is increased in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis. TNFα activates mitogen-activated kinase kinase (MEK)/extracellular regulated kinase (ERK) in chondrocytes; however, the overall functional relevance of MEK/ERK to TNFα-regulated gene expression in chondrocytes is unknown.     

Influence of depression symptoms on serum tumor necrosis factor-α of patients with chronic low back pain

Introduction  

Patients with chronic low back pain (cLBP) have high rates of comorbid psychiatric disorders, mainly depression. Recent evidence suggests that depressive symptoms and pain, as interacting factors, have an effect on the circulating levels of inflammatory markers relevant to coronary artery disease. Our previous work showed a higher serum level of an inflammatory marker tumour necrosis factor-alpha (TNFα) in patients with cLBP, which did not correlate with intensity of low back pain alone. In the present study we investigated the cross-sectional associations of depressive symptoms, low back pain and their interaction with circulating levels of TNFα.     

Anti-inflammatory effect of the alpha-melanocyte stimulating hormonein animal eyes undergoing extracapsular lens extraction

In this study anti-inflammatory effects of the alpha-melanocyte stimulating hormone (α-MSH) on ocular inflammation caused by extracapsular lens extraction (ECLE) have been investigated and the potential mechanism of an anti-inflammatory effect is discussed. Pigmented rabbit eyes after ECLE were treated locally with α-MSH, dexamethasone, diclofenac, or saline 4 times a day (q.i.d.) for 4 weeks. The inhibitory effect of α-MSH on infiltrating cells in the aqueous humor (AqH) was almost twice as good as that of dexamethasone or diclofenac for 3 days, 1 week, and 2 weeks after the operation. The eyes of Sprague-Dawley rats were treated with an intravenous injection of α-MSH or saline immediately after ECLE. Six hours postoperatively, the iris/ciliary body exhibited increased expression of TNF-α and IL-6 mRNAs, which were significantly decreased after α-MSH treatment. The number of activated NF-kappa B (NFκB)-positive cells in the iris/ciliary body was also significantly reduced by the α-MSH treatment. These results suggested that α-MSH could effectively reduce ocular inflammation after ECLE, and the potential mechanism for this is by down-regulating the expression of proinflammatory cytokines and inhibiting the NFκB-dependent signaling pathway.     

Addition of a sequence from α2-antiplasmin transforms human serum albumin into a blood clot component that speeds clot lysis

Background  

The plasma protein α₂-antiplasmin (α₂AP) is cross-linked to fibrin in blood clots by the transglutaminase factor XIIIa, and in that location retards clot lysis. Competition for this effect could be clinically useful in patients with thrombosis. We hypothesized that fusion of N-terminal portions of α₂-antiplasmin to human serum albumin (HSA) and production of the chimeric proteins in Pichia pastoris yeast would produce a stable and effective competitor protein.     

Synthesis of cyclic α-MSH peptides

Summary Cyclic lactam analogs of α-melanocyte stimulating hormone (α-MSH) have been shown to be potent agonists in the frog skin bioassay [Al-Obeidi, F. et al., J. Med. Chem., 32 (1989) 2555], demonstrating melanocortin-1 (MC1) receptor activity. We synthesized cyclic α-MSH(1–13) and α-MSH(4–10) lactam analogs. The peptides were synthesized using Fmoc chemistry. We improved the cyclization procedure: side chains of Asp⁵ and Lys¹⁰ from the deprotected peptide were coupled in DMF to form a cyclic lactam, using an excess of PyBOP reagent and DIEA as a base. The cyclization reaction was completed within 1 h and was almost quantitative. We also synthesized an α-MSH analog cyclized via a disulphide bridge. The peptides were tested for their selectivity for the rat MC4 receptor. Cyclization and substitutions at position 7 dramatically influenced the selectivity for the rMC4 receptor.     

Characterization of subcellular localization and stability of a splice variant of G alphai2

Background  

Alternative mRNA splicing of α_i2, a heterotrimeric G protein α subunit, has been shown to produce an additional protein, termed sα_i2. In the sα_i2 splice variant, 35 novel amino acids replace the normal C-terminal 24 amino acids of α_i2. Whereas α_i2 is found predominantly at cellular plasma membranes, sα_i2 has been localized to intracellular Golgi membranes, and the unique 35 amino acids of sα_i2 have been suggested to constitute a specific targeting signal.     

Tumor necrosis factor α release in peripheral blood mononuclear cells of cutaneous lupus and dermatomyositis patients

Introduction  

Several studies have reported that TNFα is substantially increased within skin lesions of patients with discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE) and dermatomyositis (DM) compared to controls. Elevated TNFα has been reported in the sera of some patients with systemic lupus erythematosus, DLE and SCLE, but not in the sera of patients with DM. Because of the key pathogenic role of autoimmunity in these diseases, in this study we sought to evaluate TNFα production by a readily available source of immune cells (namely, peripheral blood mononuclear cells (PBMCs)) taken from controls and from patients with cutaneous lupus or DM.     

HIF-2α downregulation in the absence of functional VHL is not sufficient for renal cell differentiation

Background  

Mutational inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene has been linked to hereditary as well as sporadic clear cell renal carcinomas. The product of the VHL gene, pVHL, acts to target hypoxia-inducible factor alpha (HIF-α) subunits for ubiquitination and subsequent degradation. Using an RNA interference approach to lower levels of HIF-2α in two different renal cell lines that lack functional pVHL, we have tested the contribution of HIF-2α toward cellular pVHL activities.     

Tumour necrosis factor-α production in fibrosing alveolitis is macrophage subset specific

Background  

Previous studies have revealed that tumour necrosis factor (TNF)-α is upregulated in fibrosing alveolitis (FA) in humans. The aim of this study was to compare the TNF-α secretory profile of alveolar macrophages (AMs) and peripheral blood monocytes (Mos) of patients with cryptogenic FA and systemic sclerosis (SSc), a rheumatological disorder in which lung fibrosis can occur. In particular, we wished to assess whether TNF-α levels differ between SSc patients with FA (FASSc) and a nonfibrotic group.     

Rikkunshi-to attenuates adverse gastrointestinal symptoms induced by fluvoxamine

Background  

The α-EEG anomaly during sleep, originally associated with chronic pain, is noted in several psychiatric and medical conditions and is also present in some normal subjects. The exact significance of the α-EEG anomaly is uncertain, but it has been suggested to be a nonspecific response to a variety of noxious stimuli. We propose that attachment insecurity, which is often associated with a state of hypervigilance during wakefulness, may be associated with the α-EEG anomaly during sleep.     

Active immunization to tumor necrosis factor-α is effective in treating chronic established inflammatory disease: a long-term study in a transgenic model of arthritis

Introduction  

Passive blockade of tumor necrosis factor-alpha (TNF-α) has demonstrated high therapeutic efficiency in chronic inflammatory diseases, such as rheumatoid arthritis, although some concerns remain such as occurrence of resistance and high cost. These limitations prompted investigations of an alternative strategy to target TNF-α. This study sought to demonstrate a long-lasting therapeutic effect on established arthritis of an active immunotherapy to human (h) TNF-α and to evaluate the long-term consequences of an endogenous anti-TNF-α response.