Overview of vasculitis and vasculopathy in rheumatoid arthritis—something to think about

The vasculature plays a crucial role in inflammation and atherosclerosis associated with the pathogenesis of rheumatoid arthritis. Vasculitis in rheumatoid arthritis is associated with longstanding disease, has an important impact on a patient’s quality of life and influences patient life expectancy. Seropositivity, specific human leukocyte antigen variations, antibodies to cyclic citrullinated peptides, and cigarette smoking are among the genetic and environmental predictors of rheumatoid vasculitis. Atherosclerosis is an early and common finding in rheumatoid arthritis and it correlates with disease duration, activity, and severity. Apart from conventional risk factors such as cigarette smoking, physical inactivity, obesity, arterial hypertension, dyslipidemia and diabetes mellitus, rheumatoid arthritis-related risk factors including disease duration, severity and activity, rheumatoid factor and antibodies to cyclic citrullinated peptides status, functional impairment, C-reactive protein, radiographic changes, presence of the shared epitope, and treatment modalities are all implicated in the development of accelerated atherosclerosis. Atherosclerosis is also considered an inflammatory disease; thus, it may share common pathogenic mechanisms with rheumatic diseases such as rheumatoid arthritis. Advances in treatment of rheumatoid arthritis with disease-modifying biologic and nonbiologic agents will probably continue to reduce the incidence of vasculitis. Since the goal of treatment for rheumatoid arthritis is to decrease inflammatory burden, successful treatment may theoretically reduce the risk of accelerated atherosclerosis.     

Everything You Always Wanted to Know about Sarcopenia but Were Afraid to Ask: A Quick Guide for Radiation Oncologists (impAct oF saRcopeniA In raDiotherapy: The AFRAID Project)

Sarcopenia (SP) is a syndrome characterized by age-associated loss of skeletal muscle mass and function. SP worsens both acute and late radiation-induced toxicity, prognosis, and quality of life. Myosteatosis is a pathological infiltration of muscle tissue by adipose tissue which often precedes SP and has a proven correlation with prognosis in cancer patients. Sarcopenic obesity is considered a “hidden form” of SP (due to large fat mass) and is independently related to higher mortality and worse complications after surgery and systemic treatments with worse prognostic impact compared to SP alone. The evaluation of SP is commonly based on CT images at the level of the middle of the third lumbar vertebra. On this scan, all muscle structures are contoured and then the outlined surface area is calculated. Several studies reported a negative impact of SP on overall survival in patients undergoing RT for tumors of the head and neck, esophagus, rectum, pancreas, cervix, and lung. Furthermore, several appetite-reducing side effects of RT, along with more complex radiation-induced mechanisms, can lead to SP through, but not limited to, reduced nutrition. In particular, in pediatric patients, total body irradiation was associated with the onset of SP and other changes in body composition leading to an increased risk of cardiometabolic morbidity in surviving adults. Finally, some preliminary studies showed the possibility of effectively treating SP and preventing the worsening of SP during RT. Future studies should be able to provide information on how to prevent and manage SP before, during, or after RT, in both adult and pediatric patients.     

The role of aspirin and dipyridamole on vascular DNA synthesis and intimal hyperplasia following deendothelialization

Platelets are implicated both in acute thrombotic events and, through platelet-derived growth factor, in the development of intimal hyperplasia. We have investigated, in vivo, the influence of aspirin and dipyridamole on vascular smooth muscle cell proliferation and DNA synthesis following balloon catheter injury. Fifty-eight male, New Zealand white rabbits were divided equally into two groups; the test group was fed aspirin (14 mg/kg/day) and dipyridamole (9 mg/kg/day) from 2 days prior to surgery until sacrifice at 1, 2, 3, 4, 7, 14, or 28 days after injury. All animals were sacrificed 1 h after injection of [3H]thymidine and the smooth muscle cell DNA specific activity and total kinetic activity were determined. Intimal hyperplasia was measured by light microscopy and intimal nuclear proliferation was determined by counting nuclei per millimeter of internal elastic lamina. Nuclear proliferation was maximal at 14 days (25 +/- 1.2) but intimal hyperplasia was still increasing at 28 days. DNA specific activity after 24 hr (test: 4 +/- 2 dpm/micrograms DNA; control: 3.3 +/- 3 dpm/micrograms DNA) was similar to basal levels in uninjured rabbits. DNA synthesis peaked in both groups between the second and third day (test: 177 +/- 27 dpm/micrograms DNA; control: 185 +/- 39 dpm/micrograms DNA) and then declined slowly toward baseline values. There was no significant difference between treated and normal rabbits in either [3H]thymidine incorporation, nuclear proliferation, or development of intimal hyperplasia despite 90% inhibition of platelet aggregation and a significant reduction (78%) in [14C]serotonin release following collagen challenge (6 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypophagic and Dipsogenic Effects of Central 5-HT Injections in Pigeons

The present work describes a series of experiments designed to examine the possible role of central 5-HT circuits in the control of feeding and drinking in pigeons. Acute effects (within 1 h) of intracerebroventricular (ICV) injections of 5-HT (0, 9.7, 19.4, 38.7, 77.5, 155, and 310 nmol) in 24-h food-deprived (24FD) pigeons included strong hypophagic and dipsogenic responses at the three higher doses. Total food intake and the duration of feeding behavior were reduced, and latency for the start of eating increased. Total 1-h water intake in 5-HT–treated pigeons usually increases to reach a volume equivalent to 10% of their body weight. Similarly, potent dipsogenic effects of ICV 5-HT, but no food intake decreases, were observed in food-satiated animals. Feeding behavior induced by ICV injection of adrenaline (30 nmol) in satiated pigeons was abolished by previous (20 min before) ICV 5-HT (155 nmol) injections. Catecholamine treatment did not affected the dipsogenic effect of 5-HT injections. Decreases in food intake were similarly observed after ICV or subcutaneous injections of equimolar 5-HT doses (155 nmol) in 24FD pigeons, but systemic 5-HT injections evoked no drinking behavior. Central injections of the 5-HT_2a/2c agonist DOI (56 nmol) induced similar decreases in duration and amount of food intake in 24FD animals. No dipsogenic effect was observed with either DOI doses. In 24FD pigeons, the 5-HT_1a agonist 8-OH-DPAT (30.5 nmol) induced strong dipsogenic effects, as well as increase in food intake duration. These data may indicate an involvement of 5-HT circuits in food intake as well as in water intake control systems in the pigeon, and that serotoninergic effects in these functional domains are mediated by independent mechanisms.     

Polymer conformation and viscometric behaviour, 3. Synthesis,characterization and conformational studies in poly(mono-n-octyl itaconate)

The unperturbed dimensions and the steric factor σ of poly(mono-n-octyl itaconate) (poly-(1-carboxy-1-octyloxycarbonylmethylethylene)) were determined from the intrinsic viscosities in two solvents, using the semiempirical equation of Stockmayer and Fixman. Evidence for the existence of specific effects was found. The irregular behaviour observed, can be interpreted in terms of conformational changes and conformational transitions of the polymeric chain, induced both by solvent and temperature. The effect of the structure of the monomeric unit on the flexibility of the macromolecule is discussed.     

Antibodies contained in "M" component of some patients with multiple myeloma are directed to food antigens?

Multiple myeloma is malignant disease that is characterized in most patients, by the presence in the serum of monoclonal gamma globulins, which in agarose gel after electrophoresis appear as protein band of restricted mobility, “M” component.

The aim of this study was to determine are the antibodies contained in M-component directed to some antigen chronically present in the organism, to some of food antigens.

Seventeen patients with secretory plasmacytoma were included in the study: eight of them had IgG(kappa), three had IgG(lambda), and one had biclonal IgG(kappa) and IgA(kappa), while two had IgA(kappa), the other two IgA(lambda) and one IgM(lambda) as paraproteins. M-proteins were detected analyzing patients’ sera by agarose gel electrophoresis in 0.09 M barbital buffer. The each M-protein was confirmed by immunotyping (immunofixation) with corresponding antihuman antibodies directed to heavy or light chains of immunoglobulins. After the patients serum separation on agarose gel by electrophoresis, fresh 0.4% solution of crude gliadin (Sigma) in 1% SDS was put over the slides for immunoprecipitation.

Preliminary results showed the interaction of gliadin with patient's serum proteins present in the protein fraction of the same mobility as it was the mobility of the M-component, in 6 from 17 investigated sera.

These results are the first reporting that in sera of some patients with multiple myeloma antibodies from M-component could be directed to some of gliadin antigens.

As the serum antigliadin immunoreactivity is present in patients with gluten intolerance, celiac disease, it could be of importance to elucidate is the multiple myeloma more severe form of gluten intolerance than celiac disease.