Orally administered microencapsulated lysozyme downregulates serum AGE and reduces the severity of early-stage diabetic nephropathy.

AIM: Diabetic nephropathy is the leading cause of end-stage kidney disease in developed countries and is related to chronic hyperglycaemia. The increased production and tissue deposition of advanced glycation end products (AGE) are known to play a major role in the pathogenesis of diabetic kidney damage. This study was undertaken to determine if lysozyme (LZ), microencapsulated in orally administrable chitosan-coated alginate microspheres (MS), is effective against the early changes seen in the initial stages of diabetic nephropathy. METHODS: LZ-containing MS (MSLZ) and an equivalent dose (equidose) of nonencapsulated LZ were given as oral treatments. LZ was administered to Wistar rats for seven weeks after diabetes induction with streptozotocin. RESULTS: The results showed that microencapsulated LZ treatment significantly reduced the concentration of serum AGE in the circulation and their deposition in the kidneys. Likewise, MSLZ significantly prevented the development of microalbuminuria compared with untreated diabetic rats. Furthermore, MSLZ significantly prevented the development of glomerular and renal hypertrophy as well as overexpression of AGE receptors (RAGE). An equidose of free LZ had little or no effect whatsoever. CONCLUSION: Our study supports a relationship between serum AGE and nephropathy in diabetes, and suggests that orally administered microencapsulated LZ can exert kidney-protective activity in a diabetic animal model.

Synthesis of 11-aryl-5H-imidazo[2,1-c][1,4]benzodiazepines and their benzodiazepine and A1 adenosine binding activity.

In the context of a research program aimed at elucidating the properties of the 5H-imidazo[2,1-c][1.4]benzodiazepine system, a series of 11-aryl-5H-imidazo[2,1-c][1,4]benzodiazepines (3a-i) and their 10,11-dihydro-derivatives (4a-i) has been synthesized. The synthetic strategy includes the preparation of the aryl-[1-(2-nitrobenzyl)-1H-imidazol-2-yl]methanones (5a-i) followed by their reduction and subsequent cyclization. Affinities of compounds 3a-i and 4a-i for central benzodiazepine as well as for adenosine A1-receptors were determined by radioligand binding assays. Among the unsaturated analogues, the highest activity at both receptors is displayed by 1H-(2-thienyl) derivative 3e. The hydrogenated analogues 4a-i do not exhibit considerable binding affinity either for central benzodiazepine or for adenosine A1-receptors.

Mixed cryoglobulinemia secondary to visceral Leishmaniasis.

We describe a case of type II mixed cryoglobulinemia, with monoclonal IgMkappa rheumatoid factor, associated with visceral leishmaniasis caused by Leishmania infantum. Involvement of Leishmania antigen(s) in the formation of cryoprecipitable immune complexes was suggested by the fact that cryoglobulinemic vasculitis subsided after antiparasite therapy and that anti-Leishmania antibodies, as well as rheumatoid factor, were enriched in the cryoprecipitate. We observed 2 additional patients with visceral leishmaniasis and cryoglobulinemic vasculitis. All 3 patients had seemingly contracted leishmaniasis in Italy, were hepatitis C virus negative, and were initially diagnosed as having autoimmune disorders. These findings indicate that Leishmania can be an etiologic agent of type II mixed cryoglobulinemia. This parasitosis should be taken into consideration in the differential diagnosis of vasculitides in endemic areas.

Psoriatic arthritis: a clinical, radiological and genetic study of 58 Italian patients.

It is well known that genetic heterogeneity and/or the complex interaction of several MCH-linked risk factors can explain the onset and the broad spectrum of Psoriatic Arthritis (PsA) from the clinical point of view. Fifty-eight patients with PsA (Moll and Wright criteria), 35 men and 23 women, mean age of 45, 14, were studied; all the patients were assessed by both clinical and radiological examination, with particular attention to the sacroiliac joints. HLA typing of the patients confirmed the association between PsA and HLA-B39 (p = 0.0008) and Cw6 (p = 0.0011). In addition a significant increase in DQ2 antigen (p = 0.004) has been found. No correlation of any particular HLA antigen with clinical subsets (oligo-polyarticular peripheral PsA, axial PsA and axial with peripheral PsA) or erosive incidence of joint involvement-generally related to the duration of the disease--was found.

Scintigraphic evaluation of disease activity in rheumatoid arthritis: a comparison of technetium-99m human non-specific immunoglobulins, leucocytes and albumin nanocolloids.

Technetium-99m-labelled, non-specific, polyclonal, human immunoglobulin G (99mTc-hIG) has been used to quantify synovial inflammation in rheumatoid arthritis. A comparison was carried out between the scintigraphic results obtained with this tracer, 99mTc-hexamethylpropylene amine oxime-labelled white blood cells (99mTc-WBC) and 99mTc-albumin nanocolloids (99mTc-NC). Twenty patients affected by rheumatoid arthritis and suffering from clinically active synovitis were studied with 99mTc-hIG. The number and sites of the involved joints had been previously assessed on the basis of the presence of pain and/or swelling. A radiological examination had already been carried out on all the joints. Two days after the 99mTc-hIG scan, 10 patients (group 1) underwent 99mTc-WBC scintigraphy and the other 10 (group 2) underwent a 99mTc-NC scan. The results show that the results of 99mTc-hIG and 99mTc-NC scans are in agreement with clinical examinations in the majority of cases. However, a certain number of positive joint scans corresponding to negative clinical examinations was found. The numerical distribution of these results according to the radiological stages seems to show that 99mTc-hIG is more useful than 99mTc-NC in the initial phases of the disease. The 99mTc-WBC scan was negative in a consistent percentage of the joints previously assessed as clinically and 99mTc-hIG scan positive.

Polyostotic fibrous dysplasia involving the sternum.

The authors present a case of polyostotic fibrous dysplasia involving the sternum as well. The case is well supported the strumental and histological point of view.

A multicentre comparison of flurbiprofen and naproxen in rheumatoid arthritis: a four-week study in 118 patients.

One-hundred and eighteen patients with rheumatoid arthritis were treated for 4 weeks with flurbiprofen 300 mg/day (sixty patients) or naproxen 750 mg/day (fifty-eight patients) in a six-centre randomized trial. Flurbiprofen proved to be more effective than naproxen in reducing morning stiffness (p less than 0.01), Ritchie articular index (p less than 0.01) and number of swollen joints (p less than 0.05) and in relieving night pain (p less than 0.01). The incidence and severity of side-effects, mainly gastric, were both low and similar with flurbiprofen (17%) and naproxen (19%).