Rheumatoid Arthritis Bone Fragility Is Associated With Upregulation of IL17 and DKK1 Gene Expression

Our aim was to compare bone gene expression in rheumatoid arthritis (RA) and primary osteoporosis (OP) patients. Secondary aims were to determine the association of gene expression of the Wnt/β-catenin signaling pathway with inflammatory cytokines in the bone microenvironment and to assess the serum levels of Wnt/β-catenin proteins in both groups. RA patients referred for hip replacement surgery were recruited. Primary OP patients were used as controls. Gene expression of Wnt pathway mediators, matrix proteins, and pro-inflammatory cytokines were analyzed in bone samples. Bone turnover markers, inflammatory cytokines, and Wnt mediators were measured in serum. Twenty-two patients were included: 10 with RA and 12 with primary OP. The expressions of Wnt10b (p?=?0.034), its co-receptor LRP6 (p?=?0.041), and its negative regulator DKK1 (p?=?0.008) were upregulated in RA bone. IL17 gene expression in bone was upregulated in RA patients (p?=?0.031) and correlated positively with Wnt10b (r?=?0.810, p?=?0.015), DKK2 (r?=?0.800, p?=?0.010), and RANKL/OPG ratio (r?=?0.762, p?=?0.028). DKK2 (p?=?0.04) was significantly decreased in RA serum compared with primary OP. In conclusion, bone fragility in RA patients is induced by an unbalanced bone microenvironment and is associated with a specific gene expression pattern, namely, the upregulation of IL17 and DKK1, suggesting that the modulation of these two pathways might prevent RA systemic bone loss.     

Correlation between symptoms and course duration of upper aerodigestive tract cancer at early and advanced stages

There still are many clinical and biological aspects of the natural history of cancer of the upper aerodigestive tract to be unveiled; which in Brazil is a direct consequence of the failure of systematic prevention and early diagnosis campaigns.ObjectiveTo analyze the signs and symptoms presented by patients with the disease at initial and advanced stages. Other variables such as disease duration, general and nutritional status were considered.MethodA historical cohort study with a cross-section involving 895 subjects with cancer of the upper aerodigestive tract.ResultsClinical findings were not statistically correlated with disease progression, nor with the disease in early stages, but it showed rapid disease development.ConclusionThe results suggest a disease of insidious onset in the early stages and fast course afterwards. The long disease duration - greater than three months, was associated with worsening in general and nutritional states of patients.     

Increase in nitric oxide concentrations in serum and mononuclear cell cultures from patients with Type II reaction state of Hansen's disease

The word "reaction" is used in leprosy to describe signs and symptoms of acute inflammation. Type II reactions, including erythema nodosum leprosum (ENL) occur in the multibacillary forms of Hansen's disease. Nitric oxide (NO) could play a role in the response of the host, where a high NO production would be involved in acute inflammatory processes. In this paper we evaluate NO production in serum and in the supernatants of mononuclear cell cultures (MNCC), measured indirectly by Griess' method. The results obtained in serum showed that 52% of patients with ENL (15/29) had a production over 30 microM, distributed as follows: 8/15 had a mean concentration of 36.38 +/- ?5.71 microM; 1/15, 70.5 microM and 6/15 had a mean concentration greater than 100 microM (205.97 +/- 5 microM). Forty eight percent presented nitrite and nitrate levels lower than 30 microM (18.93 +/- 6.15). Only supernatants of mononuclear cell cultures from ENL patients collected at 120 hours of incubation presented NO production levels higher than 10 microM +/- 6.53, as compared with the supernatants from the stable polar forms of the disease (lepromatous leprosy and tuberculoid leprosy), where values were 2.52 microM +/- 1.18 and 2.69 microM +/- 1.07, respectively. These preliminary results show a different metabolic activity in the group of patients with Type II reaction state (ENL).     

A rare case of mucoepidermoid carcinoma of the nasal cavity

Mucoepidermoid carcinoma of the nasal cavity is rare. We report the case of a 57-year-old man who was evaluated for a rapidly enlarging subcutaneous mass on the nasal bridge. The tumor was diagnosed as a mucoepidermoid carcinoma. The patient underwent extensive surgical resection and postoperative radiotherapy, but 5 months later he required orbital exenteration for persistent disease. Despite these radical measures, the patient died with persistent disease 9 months following the initial evaluation. The aggressive behavior of this tumor highlights the need for physicians to be aware of the differential diagnosis, symptoms, and signs of neoplasms that originate in the nasal cavity so that prompt treatment can be instituted.     

Some immunological aspects in the reaccional states of Hansen disease

The crucial clinical problem in leprosy is represented by episodes of intense inflammation that produce nerve damage. When Mycobacterium leprae has been eliminated by means of antibiotics, the death of the bacteria is not a complete solution to the damage caused in nerves. Two of the more frequent immunopathological phenomena in Hansen's disease are Type I, reactions, known as Reversal Reactions (RR), and Type II reactions, of which the most frequent and well known are those called Erythema Nodosum Leprosum (ENL). Type II reactions have been defined as an immunologic complication in multibacillary patients. Both types of reactions are accompanied mainly by the increase of pro-inflammatory cytokines TNF-alpha, IL-1, IL-2, IL-4, IL-6, IL-8, INF-gamma, IL-10, IL-12, among others. In a retrospective analysis of a population of 150 patients of the Central Service of Dermatology, Institute of Biomedicine, where these patients were subjected to Multidrug Therapy (MDT) and MDT + inmunotherapy (IMT), both groups presented type II reactions, but the group that additionally received inmunotherapy also presented type I reactions. In the group of patients that presented ENL, it appeared to be associated with the large amount of bacilli in their lesions.