On the phonon dissipation contribution to nanoscale friction by direct contact.

The friction phenomenon is a ubiquitous manifestation of nature. Models considering phononic, electronic, magnetic, and electrostatic interactions are invoked to explain the fundamental forces involved in the friction phenomenon. In order to establish the incidence of the phonon prompting at the nanoscale friction by direct contact, we study a diamond spherical dome sliding on carbon thin films containing different amount of deuterium and hydrogen. The friction coefficient decreases by substituting hydrogen by deuterium atoms. This result is consistent with an energy dissipation vibration local mechanism from a disordered distribution of bond terminators.

Increased corticotropin-releasing hormone (CRH) expression in cutaneous lupus lesions.

OBJECTIVE: Corticotropin-releasing hormone (CRH) and pro-opiomelanocortin (POMC) axis activation leads to the production of hormones, such as adrenocorticotrophic hormone (ACTH) and the α-melanocyte stimulating hormone (α-MSH). Data regarding the role of these hormones in systemic lupus erythematosus (SLE) are scarce. In the present study we aim to evaluate the participation of this axis in the cutaneous involvement of SLE. METHODS: Seventeen SLE patients were clinically evaluated, and biopsies from affected and unaffected skin of these patients were compared with 17 healthy control individuals. Immunohistochemical analyses for CRH, ACTH, α-MSH, and MC-1R were performed, and the serum levels of α-MSH, IL-1, IL-1ra, IL-6, IL-10, IL-12p70, IL-17, TNF-α, and IFN-γ were measured. RESULTS: The affected skin of the SLE patients exhibited higher CRH expression in the deep dermis compared to the skin of the controls (p = 0.024), whereas the tissue expression of ACTH, cortisol, α-MSH and its receptor MC-1R were comparable in SLE patients and controls. Higher serum levels of IFN-γ (p = 0.041), TNF-α (p = 0.001) and IL-6 (p = 0.049) were observed in SLE patients compared with controls, while α-MSH levels were similar in both groups. CONCLUSION: The novel finding of elevated CRH expression solely in the affected skin deep dermis supports the notion of a cutaneous local dysfunction of the CRH-POMC axis in the pathogenesis of cutaneous SLE lesions.

Alpha-melanocyte stimulating hormone ameliorates disease activity in an induced murine lupus-like model.

Alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide exhibiting anti-inflammatory activity in experimental models of autoimmune diseases. However, no studies thus far have examined the effects of α-MSH on systemic lupus erythematosus (SLE). This study aimed to determine the effects of an α-MSH agonist in induced murine lupus. Here we employed female Balb/cAn mice in which lupus was induced by pristane. Groups of lupus animals were treated daily with the α-MSH analogue [Nle4, DPhe7]-α-MSH (NDP-MSH) (1·25 mg/kg) injected intraperitoneally or saline for 180 days. Normal animals comprised the control group. Arthritis incidence, plasma immunoglobulin (Ig)G isotypes, anti-nuclear antibodies (ANA) and plasma cytokines were evaluated. Renal function was assessed by proteinuria and histopathological lesion. Glomerular levels of IgG, α-smooth muscle actin (α-SMA), inducible nitric oxide synthase (iNOS), C3, CD3, melanocortin receptors (MCR)1, corticotrophin-releasing factor (CRF) and α-MSH was estimated by immunohistochemistry. When compared with normal controls, lupus animals exhibited increased arthritis, IgG levels, ANA, interleukin (IL)-6, IL-10, proteinuria and mesangial cell proliferation together with glomerular expression of α-SMA and iNOS. Glomerular expression of MCR1 was reduced in lupus animals. NDP-MSH treatment reduced arthritis scores by 70% and also diminished IgG1 and IgG2a levels and ANA incidence. In the glomerulus, NDP-MSH treatment reduced cellularity by 50% together with reducing IgG deposits, and expression levels of α-SMA, iNOS and CRF were also all decreased. Taken together, our results suggest for the first time that α-MSH treatment improves several parameters of SLE disease activity in mice, and indicate that this hormone is an interesting potential future treatment option.

Nitric oxide modulates lipopolysaccharide-induced endothelial platelet endothelial cell adhesion molecule expression via interleukin-10.

We have shown previously that nitric oxide (NO) controls platelet endothelial cell adhesion molecule (PECAM-1) expression on both neutrophils and endothelial cells under physiological conditions. Here, the molecular mechanism by which NO regulates lipopolysaccharide (LPS)-induced endothelial PECAM-1 expression and the role of interleukin (IL)-10 on this control was investigated. For this purpose, N-(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg/day for 14 days dissolved in drinking water) was used to inhibit both constitutive (cNOS) and inducible nitric oxide (iNOS) synthase activities in LPS-stimulated Wistar rats (5 mg/kg, intraperitoneally). This treatment resulted in reduced levels of serum NO. Under this condition, circulating levels of IL-10 was enhanced, secreted mainly by circulating lymphocytes, dependent on transcriptional activation, and endothelial PECAM-1 expression was reduced independently on reduced gene synthesis. The connection between NO, IL-10 and PECAM-1 expression was examined by incubating LPS-stimulated (1 µg/ml) cultured endothelial cells obtained from naive rats with supernatant of LPS-stimulated lymphocytes, which were obtained from blood of control or L-NAME-treated rats. Supernatant of LPS-stimulated lymphocytes obtained from L-NAME-treated rats, which contained higher levels of IL-10, reduced LPS-induced PECAM-1 expression by endothelial cells, and this reduction was reversed by adding the anti-IL-10 monoclonal antibody. Therefore, an association between NO, IL-10 and PECAM-1 was found and may represent a novel mechanism by which NO controls endothelial cell functions.

Hansen's disease in a general hospital: uncommon presentations and delay in diagnosis.

BACKGROUND: The question was raised as to why 'obvious' signs of leprosy, Hansen's disease (HD), are often missed by medical doctors working in a HD endemic area. METHODS: This study describes a small sample of patients who were diagnosed with HD during their hospital admission and not before. The discussion is whether the typical early signs and symptoms of HD are just not recognized, or whether unusual presentations confuse the attending physician. RESULTS: A total of 23 HD patients were hospitalized during the study period, of which 6 (26%) were only diagnosed with HD during their admission. All were classified as lepromatous leprosy (LL) with a history of signs and symptoms of HD. In nearly all patients, a suspicion of HD might have been raised earlier if a careful history and dermato-neurological examination had been done. CONCLUSIONS: Multibacillary (MB) HD, especially close to the lepromatous end of the spectrum, may mimic other diseases, and the patient can not be diagnosed without a biopsy or a slit skin smear examination. Clinicians working in a HD endemic area (Rio de Janeiro) do not always include HD in their differential diagnosis, especially when the clinical presentation is unusual. HD should be considered in all patients with skin lesions not responding to treatment, especially when they have neurological deficits, and live or have lived in an HD endemic area. Due to the increase in global travel and immigration, doctors in low endemic areas need to consider HD as a possible diagnosis.

Interrelationship of the kinin system, nitric oxide and eicosanoids in the antigen-induced arthritis in rabbits.

The aim of the present study was to investigate the interrelationship of the kinin system, nitric oxide and eicosanoids in the acute phase of antigen-induced arthritis (AIA) in rabbits. The arthritis was induced in immunized rabbits and the following parameters were evaluated 24 hours later: leukocyte influx (total and differential white cell count), vascular permeability (Evans's blue method), and synovial PMN cell infiltrate. PGE2 and LTB4 (radioimmunoassay) levels were quantified in the synovial fluid. The animals were pre-treated with 20mg/kg/day during 14 days with L-NAME or D-NAME and/or Enalapril (0.12 mg/kg/day-14 days), and/or the B2 antagonist of Bradykinin HOE 140 (0.9 mg/kg). Our results showed that L-NAME was effective in the prevention of AIA with reduction of all Inflammatory parameters analyzed. Enalapril partially reverted the L-NAME anti-inflammatory effects. The simultaneous treatment with HOE 140 abolished this reversion and returned the inflammatory parameters to the levels observed in L-NAME treated animals. Our results suggest that pressoric alterations induced by L-NAME could not account for all its anti-inflammatory action in this model of experimental arthritis. Additionally the contribution of the kinin system in AIA was characterized as well as its interaction with eicosanoids and nitric oxide.

[Intra-articular nitric oxide levels in patients with rheumatoid arthritis]. / Níveis intra-articulares de óxido nítrico em pacientes com doença reumatóide.

The aim of this study was the appraisal of the nitrite and nitrate levels in the synovial fluid of patients with rheumatoid arthritis (RA). The synovial fluid of patients with osteoarthritis (OA) was also evaluated by comparison. Demographic characteristics such as age and sex, and clinical and laboratorial parameters like duration of disease, functional class and erythrocyte sedimentation rate (ESR) were evaluated too. In the synovial fluid of all patients the total and differential leukocyte count, and the nitrite and nitrate levels determined by Griess reaction were analyzed. The results were statistically analyzed by Student's t test and correlation test. We found a significant increase in the intraarticular nitrite and nitrate levels in patients with RA when compared with OA patients (30.68 +/- 2.94 microM x 16.15 +/- 2.73 microM). We did not find any correlation between intraarticular nitrite and nitrate levels and the ESR or the total and differential leukocyte count in the RA synovial fluid. In this study we clearly found an increase in the intraarticular nitrite and nitrate levels in patients with rheumatoid arthritis.

[Role of free radicals in articular inflammatory process]. / Participação dos radicais livres na inflamação articular.

The authors review recent studies supporting the role of free radicals in the inflammatory articular process. More specifically, superoxide anion and its derived active species and nitric oxide are analyzed regarding their generation by the articular cells and tissues, their destructive activity n these specialized tissues. Likewise, effects of the inhibition of free radicals production or activity in the inflammatory process is also commented.

Nitric oxide synthase inhibitor influences prostaglandin and interleukin-1 production in experimental arthritic joints.

OBJECTIVE: To assess involvement of nitric oxide (NO) in the increase in eicosanoid and interleukin- 1 (IL-1) levels in the synovial fluid during antigen-induced arthritis (AIA) in rabbits treated with a competitive inhibitor of NO synthesis. SUBJECTS: Thirteen New Zealand White rabbits were sensitized with 5 mg of methylated bovine serum albumin (mBSA). Arthritis was induced in the knee joint by injecting 0.5 ml of a sterile solution of mBSA (2 mg/ml) into the intra-articular cavity. TREATMENT: Prior to the induction of arthritis, the animals received N-Omega-Nitro-L-Arginine Methyl Ester (LNAME) or N-Omega-Nitro-D-Arginine Methyl Ester (DNAME) for 2 weeks, both at a dose of 20 mg/kg/day mixed with drinking water. METHODS: Leukocyte efflux (total and differential white cell count), vascular permeability (Evans's blue method), synovial PMN cell infiltrate, and total nitrite (NO2.)/nitrate (NO3.) (HPLC), PGE2, TxB2, LTB4 (radioimmunoassay), and IL-1 beta (ELISA) levels were quantified in the synovial fluid. RESULTS: LNAME but not DNAME significantly suppressed leukocyte efflux and protein leakage into the articular cavity as well as synovial PMN cell infiltrate. Total NO2./NO3., PGE2 and IL-1 beta levels were significantly reduced in the synovial fluid of LNAME treated animals. TxB2 and LTB4 were not affected by LNAME treatment. CONCLUSION: These data clearly show NO involvement in the IL-1-induced PGE2 production in the synovial fluid of antigen-induced arthritis in rabbits.

Action of the 4-nitro-2-phenoximethanesulphonanilide (nimesulide) on neutrophil chemotaxis and superoxide production.

4-nitro-2-phenoximethanesulphonanilide (nimesulide) is a nonsteroidal anti-inflammatory agent that has been employed in the treatment of inflammatory diseases because of its specific actions on the inflammatory response mechanisms caused by injury. The objectives of this paper were to determine the action of this agent on two notable neutrophil functions, chemotaxis and production of the superoxide anion. These two functions were studied after the neutrophils were pre-incubated with three different concentrations of 4-nitro-2-phenoximethanesulphonanilide (0.1; 0.3 and 0.5 mN). The results obtained herein demonstrated that 4-nitro-2-phenoximethanesulphonanilide-exposed peripheral blood neutrophils from healthy subjects produced significantly less superoxide when challenged by phorbolmirystate acetate (PMA at 50 ng/ml) or formy-methionil-leucyl-phenilalanine (FMLP 10-7 M) and opsonizided zymozan (1 mg/ml). Additionally, the agent was equally effective in reducing the PMN chemotoaxis when challenged by C5a factor (2% zimozan activated solution), FMLP 10-9 M and leukotrien (3.10-7 M). The results obtained suggest that in addition to its interference in the metabolism of the aracdonic acid, the 4-nitro-2-phenoximethanesulphonanilide may interfere in a more direct fashion with the neutrophil function. This specific action may contribute to its anti-inflammatory activity.

[Role of oxygen free radicals in the physiopathology of rheumatoid arthritis]. / Participação dos radicais livres de oxigênio na fisiopatologia da artrite reumatóide.

The authors present a review of the mechanisms of free radicals production and report the results of "in vivo" and "in vitro" studies correlating these agent with the physiopathologic changes of the rheumatoid arthritis. The data reviewed in this paper support the idea of the participation of free radicals in the articular lesion. However new studies are necessary to determine the contribution of free radicals on disease development, chronicity and the efficacy of antioxidant agents.

Lymphocytes in non-immune inflammation: a specific subclass of lymphoid cells?

Rats were subjected to various experimental procedures which affected lymphocyte numbers, in an attempt to investigate the participation of individual subpopulations of these cells in the development of acute, non-immune inflammation. Deficient T function, as evidenced in neonatally thymectomized animals, or in 6-week-old animals thymectomized and afterwards exposed to multiple total-body X-ray irradiations, did not interfere with the development of the acute inflammatory responses of the animals to carrageenin. In the former circumstance, the numbers of circulating B lymphocytes, identified by the presence of surface immunoglobulins, were increased. In thymectomized and irradiated rats, the B-lymphocyte subpopulation was reduced. Circumstances causing attenuated inflammatory reactions to carrageenin resulted, first, from lymphocyte depletion by chronic drainage from the thoracic duct and, second, from irradiation of the animals with a single large dose of X-ray, the animals being tested 24 h after irradiation. B lymphocytes in blood remained within the normal range after chronic lymphatic drainage, but a large dose of X-ray markedly reduced their number. In both cases the attenuation of the responses to carrageenin did not seem to be associated with nonspecific hyporeactivity, or with the effect of the treatments on the other blood cells, It is suggested that the development of acute, non-immune inflammation is influenced by lymphoid cells which might constitute a specific subclass of cells, distinct from fully differentiated T and B lymphocytes.

Virulence in mice of epidemic strains of Salmonella typhimurium isolated from children.

The virulence of 30 multiresistant strains of Salmonella typhimurium, which produced nine severe outbreaks in children's hospitals, was tested in mice. The arithmetic mean of the 50% lethal dose (LD50) for mice was 1.37 x 10(7) colony-forming units (cfu) compared with a mean LD50 of 2.65 x 10(5) cfu for 18 normal strains (P less than 0.005). Thirteen of the epidemic strains had an LD50 of greater than 10(7) cfu and on the average were 80 times less virulent than strain CDC 9, which has been kept in the laboratory for greater than 40 years. The unexpected results show that apparently the factors determining virulence for children are not the same as those for mice, and they raise doubts about the validity of using mice to study the salmonella host-parasite relationship in humans. Genetic material carried by the transfer factor may be responsible for the altered virulence of the epidemic strains.

Acute inflammatory responses in rats with protein-calorie malnutrition.

An animal model of protein-calorie malnutrition (PCM) was produced by keeping rats on a protein-free diet during the 13-day interval which followed the period of normal lactation. Malnutrition was characterized by reduction in body weight, in plasma proteins, cholesterol, haemoglobin and leucocyte counts, relative to controls from the same litter receiving a balanced diet. Acute inflammatory responses induced in these animals by carrageenin or staphylococci suspensions, differed markedly from those evoked in matching controls: the resulting oedema developed more slowly and yet persisted for longer intervals; Evans blue, injected i.v., leaked into the inflamed areas in smaller quantities; reduced cell migration to the site of the lesion was observed. The slow development of the response was attributed to the decreased levels of circulating proteins and its persistency to a defective drainage of exuded material. It is concluded that PCM can impair the capacity of response to noxious stimuli, thus rendering the animals more susceptible to infections.