Gender differences in coping with musculoskeletal pain

Gender differences in coping with musculoskeletal pain were cross-sectionally investigated, using questionnaires (Coping Strategies Questionnaire), in 446 Swedish patients (mean age 46 years, 72% women) seeking care for their ailments. Compared to male patients, women reported more disability, a larger consumption of analgesics, more work strain, higher levels of posttraumatic stress reactions, a lower self-esteem, and higher scores for the Coping Strategies Questionnaire indexes: diverting attention, praying/hoping, catastrophizing, increased behavioural activity, and pain behaviours. All gender differencesin coping were ruled out in multivariate analyses, except for the association between the interaction term Gender x Posttraumatic Stress Reactions and Catastrophizing. Among women, catastrophizing was positively associated with posttraumatic stress reactions, perceived disability, and the number of previous treatments for pain.Nosuch associations were found among men. Women’s poorer capacity to cope with musculoskeletal pain is related to higher level of emotional distress, greater disability, and a history of treatments for pain.     

Innate immune receptor NOD2 promotes vascular inflammation and formation of lipid‐rich necrotic cores in hypercholesterolemic mice

Atherosclerosis is an inflammatory disease associated with the activation of innate immune TLRs and nucleotide‐binding oligomerization domain‐containing protein (NOD)‐like receptor pathways. However, the function of most innate immune receptors in atherosclerosis remains unclear. Here, we show that NOD2 is a crucial innate immune receptor influencing vascular inflammation and atherosclerosis severity. 10‐week stimulation with muramyl dipeptide (MDP), the NOD2 cognate ligand, aggravated atherosclerosis, as indicated by the augmented lesion burden, increased vascular inflammation and enlarged lipid‐rich necrotic cores in Ldlr^?/? mice. Myeloid‐specific ablation of NOD2, but not its downstream kinase, receptor‐interacting serine/threonine‐protein kinase 2, restrained the expansion of the lipid‐rich necrotic core in Ldlr^?/? chimeric mice. In vitro stimulation of macrophages with MDP enhanced the uptake of oxidized low‐density lipoprotein and impaired cholesterol efflux in concordance with upregulation of scavenger receptor A1/2 and downregulation of ATP‐binding cassette transporter A1. Ex vivo stimulation of human carotid plaques with MDP led to increased activation of inflammatory signaling pathways p38 MAPK and NF‐κB‐mediated release of proinflammatory cytokines. Altogether, this study suggests that NOD2 contributes to the expansion of the lipid‐rich necrotic core and promotes vascular inflammation in atherosclerosis.     

MICA4/HLA-DRB1*04/TNF1 haplotype is associated with mixed connective tissue disease in Swedish patients

In order to investigate major histocompatibility complex (MHC) class I chain-related gene A (MICA), tumor necrosis factor (TNFa), -308TNFA, and human leukocyte antigen (HLA-DR/DQ) polymorphisms in mixed connective tissue disease (MCTD), we analyzed 24 patients and 229 healthy controls from Sweden. MICA and TNFa typing was performed by polymerase chain reaction (PCR) and genotyping. HLA-DR and -DQ were genotyped using PCR-sequence specific primers (PCR-SSP) and PCR-sequence-specific oligonucleotide probe (PCR-SSOP), respectively. For analysis of -308TNFA polymorphisms we performed PCR with restriction endonuclease enzymes. We found that the MICA5.1-5.1 genotype was positively associated with MCTD. Shared epitope genes (DRB1*01 and DRB1*04) were also significantly positively associated with MCTD. Polymorphism of -308TNFA was not differently distributed in MCTD patients compared with controls. Furthermore, we demonstrated that frequencies of three estimated haplotypes were increased in MCTD patients compared with controls. Interestingly, the haplotype with MICA allele 4 together with DRB1*04 and TNF1 alleles gives the most specific pattern for MCTD patients compared with controls. Our study demonstrates a clear contribution of HLA loci in susceptibility to MCTD in the Swedish population. Susceptibility to MCTD may be linked to the MICA4/HLA-DRB1*04/TNF1 haplotype and MICA 5.1-5.1 genotype. Mixed connective tissue disease was also associated with shared epitope genes, which in RA has been associated with a more severe disease. Whether these genotypes affect the clinical phenotype of MCTD needs to be determined.     

Rectal Nitric Oxide Gas and Stool Cytokine Levels during the Course of Infectious Gastroenteritis

Nitric oxide (NO) is known to be an important inflammatory mediator with a potential role in gastrointestinal diseases. We prospectively studied the luminal NO levels in 51 patients with infectious gastroenteritis, 35 patients with nonenteric bacterial infections, and 11 healthy control subjects. The levels of proinflammatory cytokines were simultaneously measured in the stools of patients with gastroenteritis. Rectal gas was sampled with balloon catheters made of silicone and was analyzed for NO levels by chemiluminescence. The median rectal NO level was 2,450 ppb in the acute phase of gastroenteritis and gradually decreased to 225 ppb after 3 to 8 weeks, whereas the median NO values were 150 ppb in patients with nonenteric bacterial infections and 100 ppb in healthy control subjects. Patients with Salmonella, Shigella, and Campylobacter infections generally had more severe symptoms and a higher median NO level (17,250 ppb) than patients with Clostridium difficile-associated diarrhea (median NO value, 275 ppb). Interleukin-1β levels were elevated in 82% of the patients at disease onset and decreased during the convalescent phase. In contrast, gamma interferon was detected in only 16% of the patients and was predominantly collected in stool samples collected during the subacute and convalescent stages. Our data point to the possibility of using this easy, minimally invasive method for luminal NO measurement as a diagnostic tool, among others, to evaluate the degree of intestinal inflammation in patients with infectious gastroenteritis.     

Chemotactic properties of retained maxillary sinus secretions

The chemotactic activity of 82 aspirated maxillary sinus secretions obtained from 32 sinuses in 29 patients was assayed with a modified Boyden chamber technique. The secretions were also analysed with respect to the proteolytic activity according to a modification of a technique described by Moroz. In only 3 of 24 sinus secretions obtained from untreated patients with purulent or mucopurulent sinusitis, but in 5 of 8 serous secretions from untreated patients with serous sinusitis a chemotactic activity exceeding random migration was found. A high proteolytic activity was found to be incompatible with a high chemotactic activity. Regarding mucopurulent and purulent sinusitis, treatment by repeated antral aspiration resulted in an increase of the proportion of chemotactically active secretions and a decrease of the proteolytic activity. Repeated antral aspirations in patients with serous sinusitis resulted in less uniform changes of the chemotactic activity.     

Origin and distribution of capsaicin-sensitive substance P-immunoreactive nerves in the nasal mucosa

In immunohistochemical studies, substance P-immunoreactivity (SP-IR) was found in a population of trigeminal ganglion cells in guinea pig, rat and cat. SP-IR nerve endings were found in the spinal trigeminal nucleus, around sphenopalatine ganglion cells, around blood vessels, as well as under and within the epithelium of the nasal mucosa. Ligation and denervation experiments in the cat indicated that the SP-IR nerves in the sphenopalatine ganglion and the nasal mucosa are of trigeminal origin. Capsaicin pretreatment of guinea pigs and rats resulted in a selective loss of the SP-IR nerves in the nasal mucosa and sphenopalatine ganglion, while the parasympathetic and sympathetic nerves were still present.     

Development of posterior capsule opacification in the rabbit

PURPOSE: The aim of the present study was to characterize the development of after-cataract in the rabbit by measuring its wet weight, protein, DNA and glycosaminoglycan (GAG) contents and using Scheimpflug and slitlamp analysis. Further, aqueous humor (AqH) leukocytes, protein and lens epithelial cell proliferation activity were determined. METHODS: AqH was collected and capsular bags including after-cataract were dissected free on days 0, 1, 7, 14, 28 and 56 after cataract surgery. The wet weights were determined and the contents of DNA, protein and GAG in the capsular bags including after-cataract were analyzed. AqH was analyzed for leukocytes, protein and proliferative activity. In another set of experiments, rabbit eyes were analyzed by the Scheimpflug technique and slitlamp examination on days 0, 1, 7, 14, 28 and 56 after cataract surgery. The wet weight of the capsular bag with the after-cataract was also determined. RESULTS: An increase was found in the wet weight (480%) and the contents of protein (221%), DNA (945%) and GAG (336%) of the capsular bags including after-cataract during the experimental period. In the AqH, all 3 variables measured, leukocytes, protein and proliferative activity, reached their highest levels on day 1 after surgery. In the second set of experiments, the wet weight of the capsular bag including after-cataract increased by 391% during the 56-day experimental period. Posterior capsule opacification (PCO), as measured by Scheimpflug analysis, increased from 0.8 to 81.7% and the scores of Elschnig's pearls as well as fibrosis, analyzed by slitlamp, increased from 0.0 to 2.8 and 3.0, respectively. CONCLUSIONS: This study shows that the same components that are reported to be important in human PCO are also components of PCO in the rabbit. Thus, the rabbit model seems to accurately reflect human PCO development, and because PCO develops much faster in rabbits that would make the rabbit model suitable for studies to elucidate human PCO development.     

Expression of cox-2, tie-2 and glycodelin by megakaryocytes in patients with chronic myeloid leukaemia and polycythaemia vera

When evaluating bone marrow sections for markers of neo-angiogenesis, we found that megakaryocytes stained markedly positive for cyclooxygenase-2 (Cox-2), Tie-2 and glycodelin. This apparently novel finding was further evaluated for disease-specific variations. Bone marrow sections from two patient groups, known to be characterized by clonal megakaryocytopoiesis, viz. chronic myeloid leukaemia and polycythaemia vera, stained, however, similarly to healthy marrows for these markers. The biochemical background and clinical significance of Cox-2, Tie-2 and glycodelin remains to be elucidated.