Magnetotransport and ARPES studies of the topological insulators Sb2Te3 and Bi2Te3 grown by MOCVD on large-area Si substrates.

Recently, the topological insulators (TIs) antimony telluride (Sb2Te3) and bismuth telluride (Bi2Te3) are attracting high interest for applications based on spin-charge interconversion mechanisms. Aiming to make a step toward the technology transfer, it is of major importance to achieve and investigate epitaxial quality-TIs on large area Si-based substrates. In view of that, we report here magnetotransport and angle-resolved photoemission spectroscopy (ARPES) studies on Sb2Te3 and Bi2Te3 thin films grown by metal organic chemical vapor deposition (MOCVD) on top of 4″ Si(111) substrates. Clear weak antilocalization (WAL) effects are observed in both TIs, proving the existence of quantum transport mechanism, and the data are successfully interpreted in the framework of the Hikami-Larkin-Nagaoka model. Further, by dedicated magnetotransport experiments, it has been confirmed that the investigated WAL originates from two-dimensional (2D) topological states. ARPES has been performed ex-situ, and in both TIs the gapless Dirac cones have been observed and attributed to the topological surface states. Combining the proofs of the existence of quantum 2D transport as deduced from the analysis of the magnetoconductance curve with the direct observation of the Dirac-like band structure revealed by the ARPES spectra, it is possible to unambiguously confirm the topological nature of our Sb2Te3 and Bi2Te3 thin films. The results obtained on thin films grown by MOCVD on 4'' Si(111) substrate mark an important step towards the technology transfer of the topological insulators studied in this work.

TRPM7 and MagT1 regulate the proliferation of osteoblast-like SaOS-2 cells through different mechanisms.

A correct magnesium (Mg2+) intake is essential for bone health. In particular, Mg2+ deficiency inhibits the proliferation of osteoblast-like SaOS-2 cells by increasing nitric oxide (NO) production through the upregulation of inducible NO synthase. At the moment, little is known about the expression and the role of TRPM7, a channel/enzyme involved in Mg2+ uptake, and MagT1, a Mg2+ selective transporter, in SaOS-2 cells. Here, we demonstrate that TRPM7 is not modulated by different extracellular concentrations of Mg2+ and its silencing exacerbates growth inhibition exerted by low Mg2+ through the activation of inducible NO synthase and consequent accumulation of NO. Moreover, MagT1 is upregulated in SaOS-2 cultured in high Mg2+ and its silencing inhibits the growth of SaOS-2 cultured in media containing physiological or high Mg2+, without any modulation of NO production. We propose that TRPM7 and MagT1 are both involved in regulating SaOS-2 proliferation through different mechanisms.

Listening to the neurological teams for multiple sclerosis: the SMART project.

OBJECTIVE: Aim of the research was to define the quality of life of Italian neurologists and nurses' professional caring for multiple sclerosis, to understand their living the clinical practice and identify possible signals of compassion fatigue. MATERIAL AND METHODS: One hundred five neurologists and nurses from 30 Italian multiple sclerosis centres were involved in an online quali-quantitative survey on the organization of care, combined with the Satisfaction and Compassion Fatigue Test and a collection of narratives. Descriptive statistics of the quantitative data were integrated with the results obtained by the narrative medicine methods of analysis. RESULTS: Most of the practitioners were neurologists, 46 average years old, 69% women, 43% part time dedicated to multiple sclerosis. An increased number of patients in the last 3 years were referred in 29 centres. Differences were found between neurologists and nurses. Physicians showed higher risks of burnout, reporting intensive working paces, lack of medical personnel, and anxiety caused by the precarious employment conditions. Nurses appeared more satisfied, although the reference to the lack of spaces, and the cross professional roles risk of compassion fatigue. Both positive and negative relationships of care were depicted as influencing the professional quality of life. CONCLUSION: The interviewed neurological teams need to limit the risk of compassion fatigue, which appeared from the first years of the career. The prevalence of the risk among neurologists suggests more awareness among scientific societies and health care managers on the risk for this category, as first step to prevent it.

[Food addiction]. / L'addiction à la nourriture.

Food addiction is a common term used in everyday language by obese patients. Although the neurobiological evidence points to some similarities between addictive mechanisms and the consumption of certain foods, this diagnosis is not yet officially recognized. After a brief history of food addiction compared to other eating disorders, we review the neurobiological processes underlying this concept. A food addiction assessment tool is presented and discussed with the current literature and new classifications of the DSM-5. The concept of food addiction needs to be rethought and requires further research.

[How to lose weight effectively and in a sustainable manner: a review of current topics]. / Comment perdre du poids de manière efficace et durable: une revue de l'actualité.

There is a lot of conflicting information regarding the best way to lose weight, especially regarding food diets. A recent study compared the different diets and ultimately revealed that there is no significant difference in their efficacy for weight loss. Furthermore, it is recommended to lose weight gradually because rapid weight loss was a risk factor for more rapid and important weight regain. This notion has been challenged by a study that compared the two approaches and demonstrated that the rate of weight loss has no influence on weight regain. Ultimately, the key is to develop strategies that are best suited to the patient, so that he can adhere more easily and maintain his efforts on the long run.

Muscle expressions of MGF, IGF-IEa, and myostatin in intact and hypophysectomized rats: effects of rhGH and testosterone alone or combined.

Myostatin and mechano-growth factor (MGF), an isoform of insulin-like growth factor-I (IGF-I), are two important regulators of muscle hypertrophy. The aim of the present study was to investigate the effects of recombinant human growth hormone (rhGH) and/or testosterone on muscle MGF/IGF-IEa/myostatin expression in intact and hypophysectomized rats treated for 15 d with 1) saline or rhGH, 2) sesame oil or testosterone, 3) saline+sesame oil, or rhGH+testosterone (first experiment) or for 7 d with saline or rhGH (second experiment). Animals were killed by decapitation 24 h or 4 d after the last injection (first or second experiment, respectively). Muscle expressions of MGF, IGF-IEa, and myostatin were determined by RT-PCR. A significant increase in the weight of gastrocnemius muscle was observed only in hypophysectomized rats treated with rhGH alone or in combination with testosterone. Administration of rhGH to hypophysectomized rats caused a marked increase in both MGF and IGF-IEa muscle mRNA levels (without any change in the muscle expression of myostatin), an effect that was abolished when testosterone was combined with rhGH. Conversely, in intact rats rhGH increased myostatin muscle mRNA levels without affecting those of MGF and IGF-IEa. Testosterone, alone or combined with rhGH, induced an inhibition of myostatin expression in the muscle of intact rats, but did not change muscle paradigms of hypophysectomized rats. In conclusion, rhGH and/or testosterone anabolic effects in the muscle are mediated by a different expression of MGF/IGF-IEa/myostatin, which is related to the pituitary function.

Interferon beta-1a slows progression of brain atrophy in relapsing-remitting multiple sclerosis predominantly by reducing gray matter atrophy.

BACKGROUND: Brain atrophy, as assessed by magnetic resonance imaging (MRI), has been correlated with disability in patients with multiple sclerosis (MS). Recent evidence indicates that both white matter (WM) and gray matter (GM) are subject to atrophy in patients with MS. Although neurological deficiencies in MS are primarily due to loss of WM, the clinical significance of GM atrophy has not been fully explored in MS. METHODS: We have undertaken a three-year, open-label study, comparing 26 patients who elected to receive intramuscular interferon beta-1a (IFN beta-1a) therapy, with 28 patients who elected not to receive therapy. Both groups had quantitative cranial MRI scans at study entry and after three years, and standardized clinical assessments every six months. Brain parenchymal fraction (BPF), GM fraction (GMF), and WM fraction (WMF) percent changes were calculated, and T2- and T1-lesion volumes (LVs) assessed. RESULTS: After three years, mean percent (%) change in BPF favored the IFN beta-1a treatment group (IFN beta-1a -1.3% versus the control group -2.5%, P=0.009), as did the mean percent change in GMF (+0.2 versus -1.4%, P=0.014), and the mean percent change in T1-LV (-9.3 versus +91.6%, P=0.011). At the end of the study, there was a significant within-patient decrease in BPF for both groups (P=0.02 for the IFN beta-1a treatment group, and P<0.001 for the control group), a significant within-patient decrease in WMF for the IFN beta-1a treatment group (P=0.01), and a significant decrease in GMF for the control group (P=0.013) when compared with baseline. CONCLUSION: Over a three-year period, treatment with IFN beta-1a significantly slowed the progression of whole-brain and GM atrophy, and of T1-hypointense LV accumulation, when compared with the control group.

Long-term effects of intravenous high dose methylprednisolone pulses on bone mineral density in patients with multiple sclerosis.

To determine the effects of high dose methylprednisolone (HDMP) pulses on bone mineral density (BMD) in patients with multiple sclerosis (MS), we studied 25 MS patients who received regular pulses of HDMP as well as pulses of HDMP for relapses, 18 MS patients who received HDMP at the same dose schedule only for relapses, and 61 healthy controls. We measured BMDs at lumbar spine and femoral neck and we assessed biochemical markers of bone metabolism and turnover. The average lifetime dosage of MP was 75.4 (SD 11.9) g in the pulsed HDMP group and 28.6 (SD 18.3) g in the HDMP for relapses group (P < 0.0001). Two MS patients (4.7%) and four controls (6.6%) had osteoporosis (P = NS), whereas 25 patients with MS (58.1%) and 21 controls (34.4%) had osteopenia (P = 0.016). BMDs measured at lumbar spine and femoral neck and biochemical indices of bone metabolism did not differ in MS patients and controls. BMD measures were not associated with lifetime methylprednisolone dosage. In partial correlation analysis, controlling for age, gender and menopausal status there was a significant inverse correlation between BMD at femoral neck and Expanded Disability Status Scale (EDSS) score (r = -0.31, P = 0.05). In conclusion, treatment with repeated HDMP pulses was not associated with osteoporosis in patients with MS who participated in a trial of methylprednisolone. However, osteopenia was observed more frequently in MS patients than healthy controls. Our data are reassuring, as them suggest that repeated pulses of methylprednisolone do not result in substantially increased risk of osteoporosis in MS patients. Moreover, osteopenia was found only in patients treated for relapses, who had a significantly higher EDSS score than patients in the HDMP group, suggesting that decreased mobility may contribute to bone loss more than corticosteroid use. BMD should be monitored in patients with MS, regardless of the use of methylprednisolone.

Risk factors of multiple sclerosis: a case-control study.

We assessed the risk of multiple sclerosis (MS) associated with a series of putative risk factors. We studied 140 patients (90 women) with MS (mean age, 42.1 years; SD= 10.2 years; disease duration, 10.9 years, SD= 7.5 years) and 131 sex-and age-matched controls. Using a structured questionnaire, we collected information related to demographic data, socio-economic status, education, ethnicity, changes of domiciles, migration, occupation, environmental, nutritional and hormonal factors, exposure to various bacterial and viral agents, vaccinations, and family history of diseases. In multiple logistic regression analysis, we found independent risk factors of MS to be: familiarity for MS (OR= 12.1; 95% CI, 1.3-110.7), autoimmune diseases (OR= 3.8; 95% CI, 2.0-7.1) and migraine (OR= 8.7; 95% CI, 1.0-75.4); comorbidity with autoimmune disease (OR= 6.8; 95% CI, 1.4-32.0) and migraine (OR= 13.5; 95% CI, 1.5-116.6); and vaccination against measles (OR= 92.2; 95%, 12.1-700.2). Familial susceptibility to MS, autoimmune diseases and migraine, and vaccination to measles are associated with an increased risk of MS. The data collected in this study are confirmatory and support the hypothesis that etiology of MS constitutes the effect of interplay between genetic and environmental risk factors. However, the relatively small number of cases and controls prevents firm conclusions.

Correlation of sexual dysfunction and brain magnetic resonance imaging in multiple sclerosis.

Sixty-two patients (40 women and 22 men) with multiple sclerosis (MS) were examined with 1.5 tesla magnetic resonance imaging (MRI) of the brain. Information on sexual and sphincteric disturbances has been collected, and data on disability, independence, cognitive performances and psychological functioning have been assessed. Calculations of T1- and T2-lesion load (LL) of total brain, frontal lobes and pons have been performed using a reproducible semiautomated technique. Whole brain, frontal and pontine atrophies were estimated using a normalized measure, the brain parenchymal fraction (BPF), obtained with a computerized interactive program. When comparing patients with and without sexual dysfunction (SD), there were no differences in total brain, frontal and pontine T1- and T2-LL, as well as in measures of whole brain and frontal atrophy. The only significant difference was in the pontine BPF (P = 0.026). In linear multiple regression analysis, SD was associated with depression (R = 0.56, P < 0.001) and, after adjusting for depression and anxiety, with bladder dysfunction (R = 0.43, P = 0.003) and pontine BPF (R = 0.56, P < 0.001). No association between SD and any of the measures of T1- and T2-LL was found. The findings showed a relationship between SD and pontine atrophy, confirmed the correlation of SD with bladder dysfunction and highlighted the role of psychological factors in determining SD.

Extended lymph node dissection for gastric cancer: results of a prospective, multi-centre analysis of morbidity and mortality in 118 consecutive cases.

This study reports interim data on post-operative morbidity, hospital mortality and duration of hospital stay of Italian patients undergoing extended lymph-node dissection combined with a pancreas-preserving technique for gastric cancer. Of the 218 patients admitted to one of eight general and/or university hospitals in North Italy, 118 were enrolled in the trial. Eligible patients presented with proven primary adenocarcinoma of the stomach without clinical evidence of distant, peritoneal and/or liver metastasis, or metastasis in para-aortic and retropancreatic nodes at intraoperative biopsy. Patients underwent the extended procedure as described by the Japanese Research Society for the Study of Gastric Cancer, following the Maruyama pancreas-preserving technique. A strict quality control system was used to ensure the performance of a standard surgical treatment. A surgeon of the reference centre (M.D.), who stayed at the National Cancer Center Hospital in Tokyo to learn the D2 technique from a specialist Japanese surgeon, became the trial supervisor and assisted each surgeon in all the Italian participating centres. The patients were staged according both to the TNM system and to the General Rules for the Gastric Cancer Study in Surgery and Pathology. Post-operative surgical complications developed in 21 patients (17.8%). The non-surgical complication rate was 2.5%. Reoperation was necessary in six patients (5%), all of whom survived. The 30-day mortality rate for the eligible group was 2.5%. The overall hospital mortality was the same. Total gastrectomy was associated with a slightly higher operative mortality (4.5% vs 1.3%). Only one patient died from an anastomotic leak. The rate of leakages was higher after total than after distal gastrectomy (15.9 vs 5.4%); the association of splenectomy and pancreatectomy worsened the morbidity rate. D2 lymphadenectomy with pancreas-preserving technique, when performed at experienced centres, seems a feasible and safe technique for the radical treatment of gastric cancer in selected Western patients.

Effect of nucleoside analogs on neurite regeneration and mitochondrial DNA synthesis in PC-12 cells.

The effects of several anti-human immunodeficiency virus nucleoside analogs were examined on neurite regeneration and mitochondrial DNA (mtDNA) synthesis in nerve growth factor-primed PC-12 cells. Under pharmacologically relevant concentrations, the exposure of cells to 2',3'-dideoxyinosine (ddI), 2',3'-dideoxycytidine (ddC) and 2',3'-didehydro-3'-deoxythymidine (d4T) led to a marked dose-dependent inhibition of neurite regeneration with a 50% inhibitory concentration approximating 1, 5 and 15 microM, respectively. In contrast, 3'-azido-3'-deoxythymidine (AZT) and beta-L-2',3'-dideoxy-3'-thiacytidine (3TC) had no effect on neurite regeneration. Inhibition of mtDNA synthesis by ddI was dose dependent, and ddC at a concentration of 10 microM strongly reduced mtDNA content by >75%. However, no inhibition of mtDNA synthesis was detected in cells exposed to 10 microM 3TC or d4T and to 25 microM AZT, suggesting a lack of definite correlation between mtDNA depletion and blockage of neurite regeneration. High performance liquid chromatographic analysis demonstrated that AZT, ddC, 3TC and d4T were anabolized to their respective monophosphate, diphosphate and triphosphate derivatives in the PC-12 cells. In addition, d4T was phosphorylated to form its monophosphate, diphosphate and triphosphate derivatives in isolated mitochondria, whereas ddC was metabolized only to its monophosphate form and no phosphorylated metabolites of 3TC were detected under the same conditions. In summary, the peripheral neuropathy induced by ddC and ddI in patients with acquired immune deficiency syndrome may be accounted for by the depletion of mtDNA content in the neurons. As for d4T, some other mechanism(s) may be involved in its clinical neurotoxicity. Both AZT and 3TC lacked any substantial toxicity in our in vitro model, which is in agreement with the clinical action of these drugs.

Clinical findings in a family with familial adenomatous polyposis and a missense mutation of the adenomatous polyposis coli gene.

BACKGROUND: More than 100 different mutations in the adenomatous polyposis coli (APC) gene have been identified; virtually all lead to the production of a truncated protein. Clinical details of patients with missense mutations undoubtedly cosegregating with the disease have not been reported and may be relevant in understanding the APC protein function. METHODS: In one family with familial adenomatous polyposis (FAP) the APC gene was analyzed by SSCP and sequencing of the aberrant SSCP band. RESULTS: A missense mutation in exon 15 at nucleotide 4921 segregating with the disease was observed. This predicts a tryptophan instead of an arginine at amino acid 1641 of the APC protein. No such mutation was present in 100 control subjects. CONCLUSIONS: In this family the colonic manifestations are as expected for classical FAP. However, the occurrence of congenital hypertrophy of the retinal pigment epithelium is unusual, owing to the inconsistency of this manifestation between family members and because congenital hypertrophy of the retinal pigment epithelium is generally absent when mutations are after codon 1387.

Ultrasonographic cross-sectional area and mean echogenicity of the superficial and deep digital flexor tendons in 50 trained thoroughbred racehorses.

Fifty Thoroughbred horses were examined. All horses had been in race training for a minimum of 4 months before examination and had worked at racing speed; 24 horses had raced. All horses were clinically sound at the time of examination. Ultrasonography was performed, using a 7.5-MHz transducer with built-in fluid offset. Videotaped images of the palmar soft tissue structures were obtained at 4, 8, 12, 16, 20 and 24 cm distal to the base of the accessory carpal bone (DACB). Images were digitized, and each image was calibrated. Values for cross-sectional area (CSA) and mean echogenicity (ME) were then determined from the cross-sectional images of the superficial digital flexor (SDF) and the deep digital flexor (DDF) tendons, using an image-analysis program. The SDF tendons were compared between right and left forelimbs at each level, and from proximal to distal on each limb, as were the DDF tendons. The relation between the SDF and DDF tendons for the same forelimb was determined at each level. There were no significant differences in CSA or ME at equivalent levels of the left and right SDF tendons. Mean (+/- SD) CSA was 1.01 +/- 0.12) cm2 at 4 cm DACB, 0.95 (+/- 0.14) cm2 at 12 cm DACB, and 1.12 (+/- 0.15) cm2 at 24 cm DACB. Adjusted ME was 2.34 (+/- 0.34) at 4 cm DACB, 2.03 (-/+- 0.38) at 12 cm DACB, and 2.04 (+/- 0.35) at 24 cm DACB. The left and right DDF tendons did not have significant differences in CSA or ME at any level. Cross-sectional area was 1.13 (+/- 0.18) cm2 at 4 cm DACB, 1.01 (+/- 0.12) cm2 at 12 cm DACB, and 1.75 (+/- 0.29) cm 2 at 24 cm DACB. Adjusted ME was 2.60 (+/-0.46) at 4 cm DACB, 2.49 (+/- 0.49) at 12 cm DACB, and 2.50 (+/- 0.44) at 24 cm DACB. At all levels, the left and right SDF tendons were smaller and less echoic than the DDF tendons of the same limb. The SDF and DDF tendons had an hour glass shape, with smallest CSA at 12 cm DACB. Mean echogenicity generally decreased for the SDF and DDF tendons from proximal to distal on the limb. These results indicate that for clinically normal trained Thoroughbred racehorses, there should be no significant difference in CSA or echogenicity between the left and right SDF tendons at equivalent distances DACB. There should be no significant differences in the left and right DDF tendons at equivalent levels DACB. The SDF tendon is usually smaller and less echoic than the corresponding DDF tendon at each level.

[Factors affecting recurrence after surgical treatment of Crohn disease]. / Fattori influenzanti la recidiva dopo trattamento chirurgico del morbo di Crohn.

Surgery does not cure Crohn's disease, but only its complications, as the recurrence rate that requires a new intervention is 6% per year. The resections performed by the surgeon should be as limited as possible, in order to avoid the consequent malabsorption. The identification of two forms of Crohn's disease, with different aggressiveness, has found that the stricturoplastic is an encouraging way of treatment for those forms with a prevalent stenotic component. A lot of studies have evaluated the relationships between recurrences and resections on margins microscopically free or affected by the disease. The aim of this study was a retrospective verification of the influence of any possible microscopical residue of the disease on the recurrence rate, evaluating whether the two different forms of aggressiveness of the disease (presence of stenosis or fistula) can influence the rate and precocity of the recurrence onset. In 37 patients operated for the first time of ileal or ileocolic resection, the overall recurrence rate was 18.9%; neither the presence of microscopically affected margins nor the presence of fistulas or stenosis has showed to have an influence on the onset of the recurrences. The only data that emerged is a greater precocity of the onset of recurrence in those patients whose disease was characterised by the presence of enteric fistulas. The forms in which fistulas and perforations were evident showed a recurrence rate not significantly higher than that of forms with stenosis only, but the period of time free from the disease was notably longer for the latter. In the end, patients in which typical granulomas were present showed a recurrence rate of just 9%, compared to 23% of patients in which granulomas were absent. MATERIALS AND METHODS. From 1980 through 1992, 61 patients affected by Crohn's disease were operated. There were 39 men and 22 women (mean age: 40.4 years). The mean length of the follow-up was 55.5 months. It was the first operation for 43 patients, while 9 had already undergone surgery in other hospitals; 9 patients showed anorectal complications. The operations performed on the patients for the first time have been ileal resection in the following localizations: duodenum-jejunum 4, jejunum and ileal 34, colic 5; the recurrences treated have been ileal-jejunum in 7 cases and colic in 2. In 2 cases of recurrence a stricturoplastic has been performed. RESULTS. The operative mortality was of 3 patients: 2 due to sepsis for anastomotic dehiscence and 1 to systemic mycosis. Four postoperative fistulas were observed. Recurrence of the disease occurred in 13 patients (26.5%), specifically in 21.4% of the patients operated for the first time and in 57.1% of those that were operated for recurrences. DISCUSSION AND CONCLUSIONS. In the treatment of Crohn's disease, it is important to identify any possible group with high risk of recurrence in order to undertake an appropriate medical prophylaxis. The results concerning the presence of microscopical disease on the resection margins are today still controversial. Some groups of authors prefer wide resection margins, some others are in favour of restricted resections. Our considerations let us assert that in those patients in which the resections have been performed on margins with microscopic presence of the disease, the interval before the recurrence occurs is not significantly shorter than that of patients with free margins. But the patients suffering from Crohn's disease with fistulae, probably need medical post-operative therapy to delay recurrences onset.

[Surgical treatment of rectal cancer: prognostic factors for long-term survival]. / Trattamento chirurgico del cancro del retto: fattori prognostici per la sopravvivenza a lungo termine.

The aim of our retrospective study was to verify the results of surgical treatment of rectal cancer in a homogeneous case series, evaluating the various factors that can influence the prognosis and long-term results. The prognostic factors taken into consideration were: Duke's stage; grading; colloid component; location of tumour; type of surgical intervention; age; sex; duration of the symptoms; length of normal rectum below the lower border of the tumour correlated to stage and grading. One hundred and sixty-five patients were operated with a radical approach: 50 abdominoperineal resections (APR) and 115 sphincter-saving resections (SSR) were performed. There were 90 males and 75 females. The mean age was 63 years. Total survival was 61.7% after 5 years and 50% after 10 years. In our study neither the age nor the sex, duration of symptoms or location of the tumours proved to have an influence on survival; while Duke's state turned out to be decisive for survival; also the colloid tumour component proved to have a worse prognosis. The 5-10-year survival rate was respectively 53.6% and 49% in the APR and 65.7% and 50.9% in the SSR (p = n.s.). The data we have collected show that APR and SSR operations have analogous efficiency.

Tumor necrosis factor alpha differentially regulates beta-endorphin concentrations and proopiomelanocortin RNA in the anterior and neurointermediate pituitary in vivo.

We analyzed the effect of tumor necrosis factor alpha (TNF-alpha) on beta-endorphin concentrations and proopiomelanocortin mRNA in the rat anterior and neurointermediate pituitaries. The intraperitoneal injection of 5 micrograms/kg TNF-alpha decreases beta-endorphin in neurointermediate pituicytes 4, 8 and 24 h after the treatment without affecting proopiomelanocortin (POMC) RNA. In contrast, in the anterior pituitary 4 h after the injection of the cytokine, POMC RNA was decreased while the peptide content was increased. These effects can be relevant to the modulation of the pituitary-adrenal axis and immune responses in conditions, such as infections, in which TNF levels are increased.

Beta-endorphin concentrations in brain areas and peritoneal macrophages in rats susceptible and resistant to experimental allergic encephalomyelitis: a possible relationship between tumor necrosis factor alpha and opioids in the disease.

Since the central nervous system and neuropeptides modulate immune functions, we investigated whether the different susceptibility of Lewis and Brown Norway rats to experimental allergic encephalomyelitis could also reflect differences in beta-endorphin and substance P concentrations in brain areas and macrophages during the development of the disease. We show that beta-endorphin concentrations increase much more in the hypothalamus and macrophages of Lewis rats during the development of the disease, while the increase is much lower or absent in Brown Norway rats. Tumor necrosis factor-alpha seems to play an important role in this difference. The administration of the opiate receptor antagonist naltrexone worsens the development of the disease, suggesting that the increase of the opioid beta-endorphin might represent a mechanism to downregulate the immune response. In both strains, the concentrations of substance P do not change.

Effect of ibuprofen and diclofenac on the chemotaxis induced by substance P and transforming growth factor-beta on human monocytes and polymorphonuclear cells.

The neuropeptide substance P and the cytokine transforming growth factor-beta are potent chemotactic factors for monocytes or polymorphonuclear cells. They are present in synovial fluid of arthritic patients, and participate in the pathogenesis of arthritis. We investigated, in vitro, the effect of two non-steroidal anti-inflammatory drugs, ibuprofen and diclofenac, on the chemotactic effect of substance P and transforming growth factor-beta at concentrations that can be present in the synovial fluid of arthritic patients. Both drugs decrease the chemotaxis induced by substance P and transforming growth factor-beta, at concentrations that can be easily reached in the synovial fluid during therapy. This event could be involved in the effect of some non-steroidal anti-inflammatory drugs on the development and progress of arthritic disease.