Unraveling the joints: a narrative review of osteoarthritis.

Osteoarthritis (OA) is a chronic and progressive degenerative disease that affects joint structures, such as the hips, knees, and hands, involving the articular cartilage, subchondral bone, ligaments, capsule, and synovium. OA is characterized by a progressive degeneration of the joint structures, resulting in pain and decreased quality of life. Local and systemic risk factors pave the way for OA development. Different phenotypes may be identified, but three main molecular mechanisms define the endotypes: the bone-driven endotype, the synovitis-driven endotype, and the cartilage-driven endotype. The hallmark of OA pathophysiology involves more than just mechanical degradation; it includes the release of pro-inflammatory mediators, such as interleukins and TNF-α, which elucidates the significant roles of metabolic syndrome, diabetes, and cellular senescence in its development. OA is distinguished by a clinical presentation that varies significantly between people and is marked by pain, stiffness, and functional impairments. The clinical course can be split into Pre-OA, Early OA, Evident OA, and End-Stage. Depending on the stage of the disease, OA diagnosis frequently necessitates a complex strategy that combines clinical evaluation to detect joint tenderness, range of motion, and joint swelling or abnormalities, medical history assessment, imaging modalities, and laboratory investigations. There is no known treatment for OA, and different therapies are usually evaluated based on the stage of the disease to minimize pain and stiffness while maintaining joint function. Treatments are divided into the reduction of modifiable risk factors, pharmacologic therapies, rehabilitation, complementary therapies, interventional pain procedures, and surgery. OA clinical heterogeneity underlines the importance of prevention, early diagnosis, and identifying the phenotype and endotype to tailor the treatment.

Validation of an original questionnaire for patients with psoriatic arthritis: the Psoriatic Arthritis Impact Profile (PAIP).

BACKGROUND AND AIMS: There is a wide evidence that Psoriatic Arthritis (PsA) as well as Psoriasis (Ps) lead to significant health problems and interfere with the patient quality of life (QoL). Even though a validated questionnaire for Ps is available, no questionnaire for PsA is currently present in literature. The aim of our work has been to confirm the efficacy of our original questionnaire as well as to validate it, through the comparison with other existing recognised and accepted questionnaires, such as MOF-SF36, HAQ, McGill Pain Questionnaire, and Zeung Self-Rating Depression and Anxiety Scales. MATERIALS AND METHODS: We have realized a questionnaire for PsA (Psoriatic Arthritis Impact Questionnaire, PAIP), in terms of psychological and rheumatological evaluation, QoL, social and economic assets. RESULTS: The statistical comparisons between PAIP and the accepted questionnaires (see above) confirm that PAIP is widely validated and represents a useful tool suitable for clinical evaluation and management of patients with PsA. CONCLUSIONS: The indexes of the correlation among the different parts of PAIP and the other questionnaires have shown positive correlations. Moreover, PAIP presents a dedicated unit for the economical and therapeutic parameters, The short time for compilation (15 minutes), the easy of comprehension of the questions, and - above all - the validation of PAIP, make our questionnaire a useful tool, suitable for the clinical management of the patients with PsA.

Hydromorphone does not influence the immune response in patients affected by chronic pain.

Hydromorphone (HMP) is a semisynthetic opioid that has been widely used over many years in the treatment of chronic moderatesevere pain. A number of studies have demonstrated the use of HMP in patients with cancer pain as safe and affective, and more recently HMP has been also utilised in the treatment of chronic degenerative pain (CDP). Then, some opioids are able to influence several immune parameters. Aim of our study was to assess HMP in patients with CDP in terms of safety and efficacy, to evaluate effects of HMP, within 2 months of observation, on cutaneous cell-mediated immunity (CCMI) as well as other basic immune parameters, and the production of interleukin-2 (IL-2) and interleukin-6 (IL-6). Results have shown that HMP does not influence CCMI nor the sieric levels of immunoglobulins or other immune parameters. Furthermore, it also has no effects on the 3rd and 4th complement fractions, on white blood cells count and T-lymphocyte subpopulations, on presence of seric autoantibodies, nor on production of IL-2 and IL-6. Therapy with HMP has not effects on the studied parameters of the immune system and does not seem to have any influence on the immune competence and immune response in patients with chronic pain.

Use of neutral protamine lispro (NPL) insulin in a patient affected by acute pancreatitis under parenteral nutrition.

Hyperglycaemia is considered the main obstacle to the activation of a correct nutritional support, even in patients not affected by diabetes mellitus. The stress associated with the acute pathology stimulates controinsular hormones and causes modifications in the glucidic metabolism. Artificial nutrition (AN), both enteral and parenteral (PN), is considered one of the main causes of hyperglycaemia in hospitalized patients. ADI-AMD recommendations underline that a long-acting insulin analogues can be used on a stabilized patient supported with PN via peristaltic pump. In the following case report, a patient under PN was given, after a surgery for acute pancreatitis, an injectable suspension of lispro NPL insulin. Our case report shows that also NPL lispro insulin subcutaneously can be used in patients under PN who need an insulin treatment and who can use a constant-flow infusion pump. Thanks to initial observations on the use of NPL insulin lispro in patients under PN we can assume the importance of such an insulin in association with AN. Clin Ter 2011; 162(3):231-234.

Functional assessment of patients with systemic sclerosis by the use of 'Six-minutes-walking-test'.

AIMS: Systemic Sclerosis (SS) is a chronic inflammatory disease of the connective tissues, characterised by alterations in the functions and structures of the small blood vessels (capillaries and arterioles) and by modifications associated with the disposition of collagen in the tissues. One of the most frequent complication of the SS is the pulmonary arterial hypertension (PAH). Aim of this study was to assess the various pathophysiological relationships betweens SS and PAH in order to establish whether the presence of this systemic disease can represent a risk factor. MATERIALS AND METHODS: Ten patients affected by SS (9 women and 1 man, with a mean age of 55.7 +/- 11.4 years) were enrolled in our study, as inpatients at Dept. of Internal Medicine and Rheumatology Unit of Perugia University School of Medicine in the "Santa Maria" General Hospital in Terni, Italy. A control group of 10 clinically healthy subjects (CHS, 9 women and 1 man, ranging in age from 35 to 55 years) was also recruited in order to obtain normal clinical data of reference In subjects recruited, we have conducted a functional evaluation, based on physical tests (6-minute-walking-test, 6MWT), equipment and laboratory, on subjects suffering from SS with suspected PAH, in order to calculate the degree of cardio-pulmonary compromission brought on by this disease, taking into consideration important variables such as age and gender. RESULTS: The 6 MWT showed that the mean value at rest of the O2 saturation (%) was 97.1 +/- 1.20, heart rate (hr/min) 76 +/- 8.8, and respiratory rate (rr/min) 20.4 +/- 2.8. HS had 98.6 +/- 0.52, 75.7 +/- 6.86, and 16.8 +/- 1.61, respectively. After the the test, the results showed that the patients had O2 saturation 93.8 +/- 3.42, hr 113 +/- 20.27, and rr 31 +/- 2.86. HS had 97.6 +/- 0.69, 90.7 +/- 5.67, and 20.1 +/- 1.59, respectively. CONCLUSIONS: Our study has confirmed the high involvement of PAH and other cardio-respiratory disturbances in patients with SS. In fact, we have verified PAP to be above the normal range in 3 out of 10 patients, while the other 3 patients presented borderline values. Because it is a simple method to conduct at low cost, in addition to being non-invasive, reproducible and well accepted, we must affirm that the 6MWT should be more utilized and exploited, especially during the fi rst phases of diagnosis. This in turn can help us to assess the patients and to determine a course of treatment which is more complex and onerous, as in therapeutic monitoring for verifying efficacy.

Evaluation of oxidative stress in rheumatoid and psoriatic arthritis and psoriasis.

INTRODUCTION: The aim of the present study is to discuss the importance of the processes of oxidative stress in the pathogenesis of certain autoimmune diseases, to search for an appropriate assessment marker, and to debate current approaches which have been proposed for the treatment of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), and Psoriasis (Ps). MATERIALS AND METHODS: The total antioxidant capacity (TAC), the thiolic capacity (TC), and the serum hydroperoxide concentration (SHC) were measured in 37 subjects: 13 with RA, 8 with PsA, 8 with Ps, and 8 healthy controls. RESULTS: SHC levels were significantly higher in patients with RA (p = 0.01), as well as in those with PsA (p = 0.005) and Ps (p = 0.002) in comparison with the control group. However, a significant reduction in the TAC values in the serum of all three groups (RA, p = 0.03; PsA, p = 0.005; Ps, p = 0.001) were observed in comparison with the healthy controls. The thiolic concentration were found to have significantly diminished in patients with RA (p =0.0005) and Ps (p = 0.0005) in comparison with the control group. Our findings have brought out the fact that the therapeutic treatment of RA using biological drugs is more than satisfactory in accord with the considerable increase in the TAC values, although not significantly, compared to those patients treated with DMARDs. CONCLUSIONS: The determination of the parameters of oxidative stress utilising these methods may be useful as a quick test, and as routine in monitoring the state of oxidative stress in patients suffering from RA, PsA, and Ps, so that a more effective treatment for ROS can be undertaken accordingly. The administration of biological drugs seems to have a role in increasing the mechanism of the barrier which the body possesses against oxidative stress.

Omeprazole induces apoptosis in normal human polymorphonuclear leucocytes.

We investigated in vitro apoptosis in human polymorphonuclear neutrophils (PMN) induced by omeprazole. This drug, both in the native (OM) and acidified (OM-HCl) form, is a potent inducer of PMN apoptosis. The effect is time- and dose-dependent. OM-HCl is more efficient than OM in inducing PMN apoptosis. In fact, after 24 h incubation in vitro at 1 x 10(-4) M OM-HCl induces apoptosis in 70% of the cell population compared to 37% induced by OM. Apoptosis induced by both forms of the drug is caspase dependent being significantly reduced by pretreating cells with the caspase 3 inhibitor (DEVDH-CHO). However, some differences in the apoptosis mechanisms between the two forms of the drug seem to exist because PMN treatment with the specific caspase 8 inhibitor (Z-IETD-FMK) only blocks OM-HCl mediated apoptosis. We observed cleavage of caspase 8 only in the cells incubated with OM-HCl while the executioner caspase 3 was activated with both forms of the drug. Furthermore, pretreatment with GM-CSF, a known activator of intracellular survival pathways in PMN, partially protected cells from OM-HCl induced apoptosis but did not contrast the apoptotic effect of OM. Cysteine cathepsin proteases also seem involved in the apoptotic mechanism of both drug forms since the specific inhibitor E64d gave a significant protection. To verify if OM-HCl induced apoptosis was dependent on the sulfenamide bound with the cell sulfhydryl groups we used molecules with thiol groups such as beta-mercaptoethanol (beta-ME) and reduced glutathione (GSH). Reactions of OM-HCl with cellular sulfhydryl groups are strongly involved in both the triggering and evolving phase of the apoptotic mechanism since significant protection from apoptosis was obtained when PMN were pretreated for 1 h with beta-ME (lipid-permeable) or GSH (lipid-impermeable). These results show that OM and OM-HCl induce apoptosis in human PMN and suggest that the second binds the sulfhydryl groups, present on the cell membrane, to then penetrate the cell thus causing a further significant increase in apoptosis. OM-induced PMN apoptosis during the treatment of gastric inflammatory disease could be an advantage for the resolution of the phlogosis state. However, this aspect should be further elucidated to assess the optimal therapeutical regimen for gastric diseases which are related to infective agents.

The therapy of Sjogren's syndrome: a review.

The Sjogren's syndrome (SS) is an chronic inflammatory autoimmune disease of the exocrine glands as well as of internal apparatus. The therapy of exocrinopathy is represented by parasympathomimetic drugs such as pilocarpine and cevimeline. The therapy of systemic manifestations, actually is represented by the inhibitors of TNF alfa, as well as leflunomide, methotrexate and cyclosporine-A, but the results are quite insufficient and disappointed. In order to the involvement of B-cell function in the pathogenesis of SS, one of the most important option in the future should be specific inhibitors of that cells.

Enhancement of lysosomal glycohydrolase activity in human primary B lymphocytes during spontaneous apoptosis.

It has been shown that lysosomes are involved in B cell apoptosis but lysosomal glycohydrolases have never been investigated during this event. In this study we determined the enzymatic activities of some lysosomal glycohydrolases in human tonsil B lymphocytes (TBL) undergoing in vitro spontaneous apoptosis. Fluorimetric methods were used to evaluate the activities of beta-hexosaminidases, alpha-mannosidase, beta-mannosidase, alpha-galactosidase, beta-glucuronidase and alpha-fucosidase. Results show that in TBL during spontaneous apoptosis, there is a significant increase in the activity of beta-hexosaminidases, alpha-mannosidase, beta-mannosidase and beta-galactosidase. Also beta-glucuronidase and alpha-fucosidase activities increase but not in a significant manner. Further studies on beta-hexosaminidases revealed that also mRNA expression of the alpha- and beta-subunits, which constitute these enzymes, increases during spontaneous TBL apoptosis. When TBL are protected from apoptosis by the thiol molecule N-acetyl-L-cysteine (NAC), there is no longer any increase in glycohydrolase activities and mRNA expression of beta-hexosaminidase alpha- and beta-subunits. This study demonstrates for the first time that the activities and expression of some lysosomal glycohydrolases are enhanced in TBL during spontaneous apoptosis and that these increases are prevented when TBL apoptosis is inhibited.

Onset of myasthenia gravis in a patient affected by rheumatoid arthritis never treated with disease-modifying anti-rheumatic drugs.

We describe a patient affected by rheumatoid arthritis (RA) that developed myasthenia gravis (MG) after 20 years of illness. The peculiarity of this case concerns both the rare association between these diseases and the fact that the patients had never assumed disease modifying antirheumatic drugs. These treatments have been associated in some clinical reports with the onset of MG during the clinical course of RA. To our knowledge this is the first case described in medical literature up to now.

Clinical efficacy and tolerance of nabumetone in articular and non-articular rheumatic disorders: personal experience during 12 weeks of treatment.

BACKGROUND: We evaluated the clinical efficacy and the tolerance of Nabumetone (N), in comparison with a pool of non-steroidal anti-inflammatory drugs (NSAIDs), in a cohort of patients affected by rheumatoid arthritis, osteoarthritis, non-articular rheumatisms and primary fibromyalgic syndrome. METHODS: One hundred and seventy patients were observed in an open-non randomized study. The patients have been recruited alternatively and subdivided into two groups: 84 patients that received N and 86 patients that received one of the other NSAIDs. All the patients affected by rheumatoid arthritis received a disease-modifying anti-rheumatic drug (OH-chloroquine, d-penicillamine, auranofin, cyclosporine-A); while benzodiazepines are administered in the patients suffering from primary fibromyalgic syndrome. A follow-up not inferior to 12 consecutive weeks was realized and the following clinical parameters were studied: spontaneous pain, provoked pain, pain on active movement, pain on passive movement, pain at rising, pain at bed time, morning stiffness, limited joint mobility, number of tender points, number of affected joints and number of swollen joints. All the patients were monitored for hematological, biochemical, urinary and clotting tests. RESULTS: The results revealed an excellent tolerability of nabumetone with a clinical efficacy not inferior to the NSAIDs' pool. Moreover, the number of drop-outs in the N-group were significantly inferior in comparison to the NSAIDs'-pool group. CONCLUSIONS: We conclude that N can be considered as effective as other NSAIDs. Moreover it seems to be better tolerated that the other NSAIDs utilized in our study.

[Beta thalassemia: motivation for screening in Terni]. / Beta-talassemia: motivazione per uno screening a Terni.

There are no definitive data on the frequency of beta-thalassaemia in the Province of Terni; a mass screening programme has not been carried out. Preliminary studies confirm that there is a strong incidence of beta-thalassaemia heterozygotes. A theory can be put forward for the presence of beta-thalassaemia trait, based on the notion of the multicentric genesis of the disorder: the malaria may have been the dominant selective factor.