PubMed Health⌕ Search

Biomedical subjects

M Cutolo

Publications and source records attributed to M Cutolo.

At least 55 records · Page 3Linked to original sources
PubMed2001

The process of aging changes the interplay of the immune, endocrine and nervous systems.

The immune, endocrine and nervous systems interact with each other by means of cytokines, hormones and neurotransmitters. Interaction is dependent on specific receptors and respective signaling pathways in target cells. During aging, changes occur on many levels of these global systems which depend on oxidative damage, non-enzymatic glycosylation, mitochondrial mutations, defects in cell cycle control, mitotic dysregulation, genome instability, telomere shortening and other chromosomal pathologies. An alteration of the numerical value of a parameter of one system can lead to changes of the numerical value of a variable of another system. In a non-linear dynamic process these changes can contribute to the aging phenotype. Although it is extremely difficult to dissect linear interrelations of three global systems during aging, this review attempts to identify some simple linear pathways. Furthermore, it is demonstrated that chronic inflammatory diseases may accelerate the aging process. This review also reveals that new statistical and computational methods are necessary to unravel the complexity of the aging process.

Aging↗
PubMed2001

Involvement of the hypothalamic--pituitary--adrenal/gonadal axis and the peripheral nervous system in rheumatoid arthritis: viewpoint based on a systemic pathogenetic role.

From the compendium presented above, the following statements become evident: 1) Inappropriately low secretion of cortisol in relation to inflammation is a typical feature of the inflammatory disease in patients with RA. 2) The secretion of adrenal androgens is significantly reduced, which is a problem in postmenopausal women and elderly men due to a lack of downstream sex hormones. 3) Serum levels of testosterone are markedly reduced in RA. 4) Sympathetic nerve fibers are markedly reduced in the synovial tissue of patients with RA, whereas proinflammatory sensory fibers (substance P) are present. 5) Substance P serves to continuously sense painful stimuli in the periphery, and the nociceptive input from the inflamed joint shows a large amplification in the spinal cord. This leads to continuous pain with stabilization of the afferent sensory input and continuous release of proinflammatory substance P into the lumen of the joint. From these facts it is obvious that alterations of the systemic antiinflammatory feedback systems contribute significantly to the pathogenesis of RA. Disease therapy directed at these alterations must provide a mechanism to replace the adrenal glands (glucocorticoids), the gonadal glands (androgens), and the sympathetic nervous system (adenosine increase by low-dose MTX, sulfasalazine, and salicylates) in order to integrate their immunosuppressive effects at the local site of synovial inflammation. Although local processes of the adaptive immune system are important in pathogenesis in the acute phase of RA, these mechanisms may be less important during the chronic phase of the disease in the absence of a specific trigger. We believe that a defect of systemic antiinflammatory feedback systems is an important factor in the perpetuation of RA. This review reinforces the belief that combined therapeutic approaches on a neuroendocrine immune basis are of crucial importance in a pathogenetically oriented therapy of RA.

Arthritis, Rheumatoid↗
PubMed2001

A comparison of cyclosporine, sulfasalazine, and symptomatic therapy in the treatment of psoriatic arthritis.

OBJECTIVE: To compare the efficacy and tolerability of cyclosporine (CSA) with that of symptomatic therapy (ST) alone and sulfasalazine (SSZ) in the treatment of psoriatic arthritis (PsA). METHODS: Twelve rheumatology centers recruited 99 patients with active PsA in a 24 week, prospective, randomized, open, controlled study. The patients were treated with CSA (3 mg/kg/day) or SSZ (2,000 mg/day) plus ST, or ST alone (nonsteroidal antiinflammatory drugs, analgesics, and/or prednisone < or = 5 mg/day). The primary endpoint was the 6 month change in pain. Analyses were on the basis of the intention-to-treat principle. RESULTS: In comparison with both SSZ and ST, there was a statistically significant difference in favor of CSA in terms of the mean changes in the pain score (p < 0.05), which was considered the primary response variable. A significant decrease in favor of CSA versus ST alone was also observed for swollen joint count (p = 0.05), tender joint count (p = 0.01), joint/pain tenderness score (p = 0.002), patient and physician global assessment by at least one point (p = 0.04 and 0.01, respectively), total Arthritis Impact Measurement Scale score (p = 0.002), and spondylitis functional index (p = 0.002). There was a statistically significant difference in the ACR 50% and ACR 70% response rates between the CSA and ST groups (p = 0.02, 0.05). Comparing the SSZ and ST alone groups, only the spondylitis functional index decreased significantly in the SSZ treated patients (p = 0.03). The Psoriasis Area and Severity Index was significantly lower in the CSA than in the ST and SSZ groups (p = 0.0001 and 0.01, respectively). Decrease in erythrocyte sedimentation rate was significant only in the SSZ versus the ST group (p = 0.02), whereas reduction in C-reactive protein was significant in the CSA treated patients compared with the ST group (p = 0.006). The most common adverse event in the CSA group was mild, reversible kidney dysfunction. CONCLUSION: The results of this open trial confirm that CSA is well tolerated by patients with PsA and suggest that it is more efficacious than ST or SSZ.

Adult↗
PubMed2000

The hypothalamic-pituitary-adrenocortical and gonadal axis function in rheumatoid arthritis.

The altered cortisol and adrenal androgen (i.e., dehydroepiandrosterone sulfate = DHEAS) secretion, observed during testing in rheumatoid arthritis (RA) patients not treated with corticosteroids, should be clearly regarded as a "relative adrenal insufficiency" in the setting of a sustained inflammatory process, as shown by high serum IL-6 levels. Androgens seem implicated in the pathophysiology of autoimmune disorders, including RA, as natural immunosuppressors. Low plasma and synovial fluid testosterone concentrations are observed in male RA patients; low plasma DHEAS levels are mainly observed in female RA patients. The menopausal peak of RA suggests that estrogens and/or progesterone deficiency also play a role in the disease, and many data indicate that estrogens suppress cellular immunity, but stimulate humoral immunity (i.e., deficiency promotes cellular Th1-type immunity). Gene polymorphisms for enzymes involved in the steroidogenesis seem to further complicate the role of sex hormones in the susceptibility to autoimmunity. Acquired changes of sex steroid metabolism seem to also play a role in the peripheral sex hormone levels. In conclusion, a complex interaction between the hypothalamus-pituitary-adrenocortical and gonadal axis functions is evident in RA.

Adrenal Insufficiency↗
PubMed2000

Different roles for androgens and estrogens in the susceptibility to autoimmune rheumatic diseases.

It is now documented that androgens and estrogens modulate susceptibility and progression to autoimmune rheumatic diseases. At any concentration, androgens seem to be primarily suppressive on cellular and humoral immunity, whereas at physiologic concentrations, estrogens seem to enhance humoral immunity. Further research should focus on the different and frequently opposite effects exerted by physiologic and pharmacologic doses of estrogens (dose-related effects). In addition to the influence of endogenous estrogen fluctuations (i.e., during pregnancy, postpartum, menstrual periods, menopause), estrogen replacement therapy, and the use of oral contraceptives, the susceptibility to autoimmunity might be increased by the environmental estrogens (xenobiotics). Further studies must be directed to the inflammatory mediators (i.e., cytokines) that seem to alter the peripheral metabolism of sex hormones and complicate the effects of sex hormones on susceptibility to autoimmunity. Finally, genetic factors might further interfere with the roles of androgens and estrogens in selected individuals.

Androgens↗
PubMed2000

Sex hormone adjuvant therapy in rheumatoid arthritis.

RA is an autoimmune rheumatic disorder resulting from the combination of several predisposing factors, including the relation between epitopes of possible triggering agents and histocompatibility epitopes, the status of the stress response system, and the sex hormone status. Estrogens are implicated as enhancers of humoral immunity, and androgens and progesterone are natural immune suppressors. Sex hormone concentrations have been evaluated in RA patients before glucocorticoid therapy and have frequently been found to be altered, especially in premenopausal women and male patients. In particular, low levels of gonadal and adrenal androgens (testosterone and DHT, DHEA and DHEAS) and a reduced androgen:estrogen ratio have been detected in body fluids (i.e., blood, synovial fluid, smears, saliva) of male and female RA patients. These observations support a possible pathogenic role for the decreased levels of the immune-suppressive androgens. Exposure to environmental estrogens (estrogenic xenobiotics), genetic polymorphisms of genes coding for hormone metabolic enzymes or receptors, and gonadal disturbances related to stress system activation (hypothalamic-pituitary-adrenocortical axis) and physiologic hormonal perturbations such as during aging, the menstrual cycle, pregnancy, the postpartum period, and menopause may interfere with the androgen:estrogen ratio. Sex hormones might exert their immune-modulating effects, at least in RA synovitis, because synovial macrophages, monocytes, and lymphocytes possess functional androgen and estrogen receptors and may metabolize gonadal hormones. The molecular basis for sex hormone adjuvant therapy in RA is thus experimentally substantiated. By considering the well-demonstrated immune-suppressive activities exerted by androgens, male hormones and their derivatives seem to be the most promising therapeutic approach. Recent studies have shown positive effects of androgen replacement therapy at least in male RA patients, particularly as adjuvant treatment. Interestingly, the increase in serum androgen metabolism induced by RA treatment with CSA should be regarded as a possible marker of androgen-mediated immune-suppressive activities exerted by CSA, at least in RA and at the level of sensitive target cells and tissues (i.e., synovial macrophages). The absence of altered serum levels of estrogens in RA patients and the reported immune-enhancing properties exerted by female hormones have represented a poor stimulus to test estrogen replacement therapy in RA. The different results obtained with OC use seem to depend on dose-related effects and the different type of response to estrogens in relation to the cytokine balance between Th1 cells (cellular immunity, i.e., RA) and Th2 cells (humoral immunity, i.e., SLE). The androgen replacement obtained directly (i.e., testosterone, DHT, DHEAS) or indirectly (i.e., antiestrogens) may represent a valuable concomitant or adjuvant treatment to be associated with other disease-modifying antirheumatic drugs (i.e., MTX, CSA) in the management of RA.

Androgens↗
PubMed2000

No evidence of an association between Helicobacter pylori infection and Raynaud phenomenon.

BACKGROUND: Raynaud phenomenon (RP) is a vasospastic condition that manifests itself as cold-induced ischemic attacks of the fingers with skin color changes. It may be classified as primary (PRP) or secondary (SRP), if associated to other diseases, mainly connective-tissue diseases. Recently, the association between PRP and Helicobacter pylori infection has been reported. The aims of this study were to evaluate the prevalence of gastric H. pylori infection in a large group of patients affected by PRP and SRP and to assess whether it was more evident in patients with more recent onset of RP. METHODS: Ninety-eight consecutive patients (93 F and 5 M), referring to our videocapillaroscopic service for the diagnosis of vascular and connective-tissue diseases, were evaluated. Forty-nine of them were affected by PRP and 49 by SRP. Patients were classified as having PRP on the basis of normal serological and immunological findings, normal videocapillaroscopic examination and exclusion of other conditions inducing RP. H. pylori infection was diagnosed by 13C-urea breath test (UBT). Two groups of 49 age-and sex-matched controls, respectively, were also evaluated. RESULTS: Patients with SRP resulted significantly older than those with PRP (P < 0.006). UBT was found positive in 22/49 patients with PRP (45%) and in 29/49 patients with SRP (59%). The positivity of the respective control groups was 36% and 53% (P = NS). There was no higher prevalence of H. pylori infection in patients with RP lasting for less than 4 years. CONCLUSIONS: The results do not confirm the previously reported high prevalence of H. pylori infection in patients with PRP. A high association was not even found between the presence of the microorganism and SRP. There was no difference in the prevalence of H. pylori infection among the subgroups with more recent onset of both PRP and SRP.

Adult↗
PubMed2000

Evidence of cerebral hypoperfusion in scleroderma patients.

OBJECTIVES: To investigate regional cerebral blood flow by (99m)Tc-hexamethylpropylenamineoxime (HMPAO) single photon emission computed tomography (SPECT) in a series of 40 patients (mean age 58.5+/-11.5 yr) affected by systemic sclerosis (SSc) in comparison with age-matched healthy controls. METHODS: Subjects affected by concomitant severe pathologies that might interfere with the interpretation of the SPECT results were excluded. SPECT findings were correlated with the severity of peripheral microvascular involvement, as assessed by nailfold videocapillaroscopy (NVC). Whenever possible, patients underwent magnetic resonance imaging (MRI) of the brain. RESULTS: Twenty-one SSc patients (52%) showed hypoperfusion in two or more regions of interest (ROIs) at the SPECT analysis. MRI was available in 14 of these patients, and was shown to be altered in eight of them (57%). One patient with both abnormal SPECT and abnormal MRI was affected by mild cognitive impairment. Transcranial Doppler sonography was normal in all but one of these patients with hypoperfusion. Nineteen patients exhibited a normal brain SPECT scan, but the MRI was shown to be altered in 3/12 of them (25%). No significant differences were found between the group of SSc patients showing hypoperfusion and those showing a normal SPECT scan regarding age, the duration of disease, the presence of vascular risk factors or damage of other organs typically involved in the disease, and the severity of peripheral microvascular involvement (NVC). CONCLUSIONS: Focal or diffuse cerebral hypoperfusion was found in more than half of the neurologically asymptomatic SSc patients studied, paralleling the incidence of altered brain MRI. The hypoperfusion was not linked to ageing and possibly reflects the cerebral location of the microangiopathic process characterizing the disease.

Adult↗
PubMed2000

The adrenal steroid status in relation to inflammatory cytokines (interleukin-6 and tumour necrosis factor) in polymyalgia rheumatica.

OBJECTIVES: To determine the correlation between inflammatory cytokines and adrenal hormones in patients with polymyalgia rheumatica (PMR) and to compare the ratio of serum cortisol and androstenedione (ASD) or dehydroepiandrosterone sulphate (DHEAS) in normal subjects with PMR patients. METHODS: In 102 patients with PMR (32 beginning and 70 chronic disease) and 31 age-matched and sex-matched healthy subjects, ASD, cortisol, DHEAS, interleukin-6 (IL-6), and tumour necrosis factor (TNF) were measured by immunometric assays. RESULTS: Serum levels of IL-6 were elevated in patients with PMR as compared with normal subjects (10.0 +/- 1.6 vs 2.1 +/- 0.1 pg/ml, P = 0.01), which was not found for TNF. In PMR patients, serum levels of IL-6 were positively correlated with serum levels of ASD (P < 0.001), cortisol (P < 0.001), and DHEAS (P = 0. 038) irrespective of corticosteroid treatment. Serum levels of cortisol in relation to IL-6 were significantly lower in patients with chronic disease and long-standing corticosteroid administration as compared with patients with recent onset of the disease and without corticosteroid therapy (P < 0.01). CONCLUSIONS: In PMR, as expected, there was an increase in IL-6 serum levels that was associated with elevated serum levels of ASD, DHEAS, and cortisol which was more marked in patients with recent-onset disease and without corticosteroids. However, serum levels of cortisol in patients with and without corticosteroids were lower than expected by considering the inflammatory status (increased IL-6). This may indicate a change in the hypothalamic-pituitary-adrenal (HPA) axis responsiveness to inflammatory stimuli such as IL-6 during chronic disease. Furthermore, there seems to be a shift of biosynthesis to cortisol in relation to DHEAS or ASD in chronic disease.

Adrenal Glands↗
PubMed2000

The hypothalamic-pituitary-adrenal and gonadal axes in rheumatoid arthritis.

The hypothalamic-pituitary-adrenal (HPA) and the hypothalamic-pituitary-gonadal (HPG) axes involvement or response to immune activation seems crucial for the control of excessive inflammatory and immune conditions such as autoimmune rheumatic diseases, including rheumatoid arthritis (RA). However, female patients seem to depend more on the HPA axis, whereas male patients seem to depend more on the HPG axis. In particular, hypoandrogenism may play a pathogenetic role in male RA patients because adrenal and gonadal androgens, both products of the HPA and HPG axes, are considered natural immunosuppressors. A significantly altered steroidogenesis of adrenal androgens (i.e., dehydroepiandrosterone sulfate, DHEAS and DHEA) in nonglucocorticoid-treated premenopausal RA patients has been described. The menopausal peak of RA suggests that estrogens and/or progesterone deficiency also play a role in the disease, and many data indicate that estrogens suppress cellular immunity, but stimulate humoral immunity (i.e., deficiency promotes cellular Th1-type immunity). A range of physical and psychosocial stressors are also implicated in the activation of the HPA axis and related HPG changes. Chronic and acute stressors appear to have different actions on immune mechanisms with experimental and human studies indicating that acute severe stressors may be even immunosuppressive, while chronic stress may enhance immune responses. The interactions between the immunological and neuroendocrine circuits is the subject of active and extensive ongoing research and might in the near future offer highly promising strategies for hormone-replacement therapies in RA.

Animals↗
PubMed2000

Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis.

OBJECTIVE: To correlate microvascular abnormalities, evaluated by nailfold videocapillaroscopy (NVC), with the duration of both Raynaud's phenomenon (RP) and systemic sclerosis (SSc) from the date of diagnosis, in a large number of patients with SSc. METHODS: Ninety-seven consecutive patients were recruited and distributed into 3 groups on the basis of the morphological NVC patterns observed: "early" (E), "active" (A), and "late" (L). In each group the age of patients, age at onset, and the duration of RP as well as of overt SSc were investigated and correlated with the different NVC pattern variables. RESULTS: The early appearance of giant capillaries and hemorrhages (E pattern) is of great relevance for the early diagnosis of SSc. Therefore, these alterations are more evident in the active phase of the disease (A pattern). Conversely, the NVC observation of loss of capillaries and vascular architectural disorganization and the presence of ramified/bushy capillaries (L pattern) represents the clearest aspect of advanced SSc microvascular damage. These morphological alterations were found to correlate significantly with the duration of both RP and SSc, as well as with age of patients (p = 0.0001). No significant differences were observed when the variables were analyzed in the patients classified as having limited cutaneous SSc or diffuse cutaneous SSc. CONCLUSION: Classification of defined major nailfold patterns may be useful in assessing the appearance and progression of sclerodermic microangiopathy. As well, nailfold changes might represent a morphological reproduction of the evolution of SSc.

Female↗