Influence of different surfactants on the physicochemical properties of elastic liposomes.

Elastic liposomes are capable to improve drug transport through the skin by acting as penetration enhancers due to the high fluidity and elasticity of the liposome membranes. Therefore, elastic liposomes were prepared and characterized to facilitate the transdermal transport of bioactive molecules. Liposomes consisted of dimyristoylphosphatidylcholine (DMPC) as the structural component, with different surfactants derived from lauric acid as elastic components: C12E5 (polyoxyethylene-5-lauryl ether), PEG4L (polyethyleneglycol-4-lauryl ester), PEG4DL (polyethylene glycol-4-dilauryl ester), PEG8L (polyethylene glycol-8-lauryl ester) and PEG8DL (polyethylene glycol-8-dilauryl ester). The elastic liposomes were characterized in terms of their phospholipid content, mean diameter, size distribution, elasticity and stability during storage, as well as their ability to incorporate surfactant and permeate through 50 nm pore size membranes. The results showed that the phospholipid phase transition temperature, the fluidity of the lipid bilayer resulting from incorporation of the surfactant and the preservation of particle integrity were factors determining the performance of the elastic liposomes in permeating through nanoporous membranes. The best results were obtained using DMPC combined with the surfactants PEG8L or PEG8DL. The findings demonstrate the potential of using elastic liposomes for transdermal administration of drugs.

Hepatitis B and C virus infections as possible risk factor for pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAC) is a very aggressive and lethal cancer, with a very poor prognosis, because of absence of early symptoms, advanced stage at presentation, early metastatic dissemination and lack of both specific tests to detect its growth in the initial phases and effective systemic therapies. To date, the causes of PAC still remain largely unknown, but multiple lines of evidence from epidemiological and laboratory researches suggest that about 15-20% of all cancers are linked in some way to chronic infection, in particular it has been shown that several viruses have a role in human carcinogenesis. The purpose of this report is to discuss the hypothesis that two well-known oncogenic viruses, Human B hepatitis (HBV) and Human C hepatitis (HCV) are a possible risk factor for this cancer. Therefore, with the aim to examine the potential link between these viruses and PAC, we performed a selection of observational studies evaluating this association and we hypothesized that some pathogenetic mechanisms involved in liver carcinogenesis might be in common with pancreatic cancer development in patients with serum markers of present or past HBV and HCV infections. To date the available observational studies performed are few, heterogeneous in design as well as in end-points and with not univocal results, nevertheless they might represent the starting-point for future larger and better designed clinical trials to define this hypothesized relationship. Should these further studies confirm an association between HBV/HCV infection and PAC, screening programs might be justified in patients with active or previous hepatitis B and C viral infection.

Au nanoparticles prepared by physical method on Si and sapphire substrates for biosensor applications.

Gold nanoparticles heavily functionalized with oligonucleotides have been used in a variety of DNA detection methods. The optical properties of three-dimensional aggregates of Au nanoparticles in solution or deposited onto suitable surfaces have been analyzed to detect hybridization processes of specific DNA sequences as possible alternatives to fluorescent labeling methods. This paper reports on the preparation of gold nanoparticles directly deposited onto the surface of silicon (Si) and sapphire (Al2O3) substrates by a physical methodology, consisting in the thermal evaporation of a thin Au film and its successive annealing. The method guarantees the preparation of monodispersed single-crystal Au nanoparticles with a strong surface plasmon resonance (SPR) peak centered at about 540 nm. We show that the changes of SPR excitation before and after DNA functionalization and subsequent hybridization of Au nanoparticles immobilized onto Si and Al2O3 substrates can be exploited to fabricate specific biosensors devices in solid phase.

Solubilization of human erythrocyte membranes by non-ionic surfactants of the polyoxyethylene alkyl ethers series.

In the present study, we investigated the interaction of the non-ionic surfactants polyoxyethylene alkyl ethers (C(n)E(m)) with erythrocyte membranes. For this purpose we have performed hemolytic assays under isosmotic conditions with five surfactants in the 8 polyoxyethylene ether series. By applying to the hemolytic curves a quantitative treatment developed for the study of surface-active compounds on biomembranes, we could calculate the surfactant/lipid molar ratios for the onset of hemolysis (R(e)(sat)) and for complete hemolysis (R(e)(sol)). This approach also allowed the calculation of the binding constants for each surfactant to the erythrocyte membrane. Results in the C(n)E(m) series were compared to those obtained for Triton X-100, a well-known non-ionic surfactant with values of cmc and HLB in the range of the alkyl ethers studied. Inside the series the lytic effect increased with the more hydrophobic homologues (C(10)E(8)

Ophthalmologic manifestations of rheumatic diseases.

OBJECTIVES: Detailed review of the manifestations of eye involvement in the context of rheumatic diseases. METHODS: An OVID Medline search of the rheumatology and ophthalmology English literature related to the eye manifestations of human rheumatic diseases from 1966 to the present was conducted by the authors. RESULTS: Analysis of 300 recent and consecutive rheumatology consultations from a large Veterans Administration Healthcare System shows that 4% are referred for eye manifestations of suspected rheumatic diseases, most commonly, anterior uveitis and keratoconjunctivitis sicca (KCS). Ocular involvement is common in the rheumatic diseases but varies among the different disorders. A literature review indicated that the most common ocular manifestations of rheumatic diseases include keratoconjunctivitis sicca, anterior uveitis, and scleritis. The most serious eye complications of the inherited connective tissue disorders are lens involvement with cataract formation or subluxation. The most significant side effects of the drugs used to treat rheumatic diseases are the maculopathy associated with anti-malarial agents and cataracts and glaucoma associated with corticosteroid use. Although many of the eye manifestations are easily recognizable, consultation with an ophthalmologist is usually necessary for optimal treatment and prevention of complications. CONCLUSIONS: The rheumatologist, in coordination with the ophthalmologist, can play a major role in detecting and managing the eye involvement in his patients to save this important sense. Understanding the varied manifestations of eye disease will permit the rheumatologist to better evaluate the activity of the rheumatic disease.

Systemic lupus erythematosus in men: a retrospective analysis in a Veterans Administration Healthcare System population.

Systemic lupus erythematosus (SLE), a connective tissue disease of unknown etiology, is generally considered to occur in women of child-bearing age and to be uncommon among men . Because of the female predominance in most studies, less is known about the disease in men. To begin to better understand lupus in men, we retrospectively analyzed all the SLE patients from all the hospitals in the Department of Veterans Affairs (VA) system, a population that is predominantly male. Between 1987 and 1996, 2614 SLE patients were retrieved from the VA databank; 2144 were male, making this the largest group of male patients with SLE reported in United States of America. Age, racial and geographic distribution, comorbidities, and mortality of the SLE patients are reported. This study suggests that SLE men in this population are older at onset of disease, have different comorbidities, and have a higher mortality at 1 year than women with SLE. These findings suggest that men with SLE have a more complex clinical course than women, although the data do not illuminate whether the comorbidities are due to or coincident with SLE. On the basis of these data, practitioners are reminded to consider SLE in the differential diagnosis for older men and be attentive to the frequent presence of comorbidities such as cardiac ischemia and neoplasms. Because of the identified regional variations in demographics, comorbidities, and mortality, this study suggests the need for future SLE studies to include data from multiple geographic areas.

Growth effects of Phaenicia sericata larval extracts on fibroblasts: mechanism for wound healing by maggot therapy.

The potential growth stimulating effects of the blow fly, Phaenicia sericata, on mammalian tissue were assessed by exposing human fibroblast tissue culture to maggot extracts. The growth effects of these extracts were compared to those of epidermal growth factor (EGF), recombinant interleukin 6 (IL6), and the insect hormone 20-hydroxyecdysone (EC). Results of dose-response experiments revealed that EGF had a maximum fibroblast stimulation at 66078 +/- 1979 counts per minute (cpm), with peak counts on day 6 of culture, as measured by [3H]-thymidine incorporation. P. sericata hemolymph (HL) and alimentary secretions (AS) and EC were also demonstrated to stimulate resting fibroblast tissue cultures, but the maximal stimulations only achieved 12% of EGF. Their growth rates plateaued between days 4 and 6. Addition of both HL and AS, as well as EC, significantly increased the growth rate of EGF-stimulated fibroblasts; AS increased the maximal stimulation of IL6-stimulated fibroblasts. These studies suggest the existence of intrinsic factors within the maggot which may be responsible for the growth-stimulating effects seen in maggot-infested wounds.

The contribution of synovial fluid lipoproteins to the chronic synovitis of rheumatoid arthritis.

Lipids in the synovial fluid of patients with active rheumatoid arthritis are elevated compared to normal synovial fluid and that of other inflammatory arthropathies. Various assumptions about the role of these lipids have been made. This study offers evidence that these lipids may contribute to the synovitis in rheumatoid arthritis through participation in the arachidonic pathway within the joint space. Phospholipase A2 activity, phospholipids, prostaglandin E2, and leukotriene B4 have been correlated in the synovial fluid and plasma of untreated rheumatoid patients and compared with that of patients with osteoarthritis.

Musculoskeletal disease in very elderly nursing home patients: does under-reporting exist?

To determine the extent of under-reporting of musculoskeletal disease among very elderly nursing home patients, 50 Veterans Affairs Nursing Home patients were evaluated by means of retrospective medical chart review. The primary caregivers' charted musculoskeletal examinations were scored objectively; then the patients completed an arthritis questionnaire, a short-form Geriatric Depression Scale assessment, and the Katz Activities of Daily Living Scale assessment. Finally, each patient underwent an objectively scored musculoskeletal examination by a rheumatologist. The results indicated that musculoskeletal disease in the very elderly nursing home patient is more prevalent than self-report or examination by the primary caregiver suggested. Brief but directed arthritis symptom questioning followed by a specialized examination were necessary to diagnose treatable musculoskeletal disease in this population.

Synovial fluid lipids and apolipoproteins: a contemporary perspective.

Normal human synovial fluid contains extremely low concentrations of lipoproteins and apolipoproteins, in sharp contrast to those found in plasma. Increased amounts of cholesterol and other lipids have been found in the synovial fluid of a chronic inflammatory joint disorder, rheumatoid arthritis (RA). More recently, apolipoproteins AI, B and E have also been found in increased amounts in RA synovial fluid. Theories have been proposed to account for this increase in the amount of apolipoproteins and for the source of lipids and lipoproteins in normal synovial fluid; however, the mechanisms have not yet been established. Lipoproteins may play dual roles in synovial fluid: A functional one in normal synovial fluid and, as some suggest, a pathologic one in the abnormal synovial fluid of certain arthritic diseases. The recent data prompt the need to define synovial fluid lipids, lipoprotein particle subfractions and their constituent apolipoproteins, as well as their respective roles in synovial fluid.

[The surgery of pulmonary metastases. The surgical indications and technical aspects of lung resections for metastases]. / La chirurgia delle metastasi polmonari. Indicazioni operatorie e aspetti tecnici delle resezioni polmonari per metastasi.

Surgery for pulmonary metastases is an accepted method of treatment for many kinds of malignant neoplasms, because of favorable results in five-year and ten-year survival. At present several technical aspects are being debate (operative indications, method of thoracic access, procedure of lung resection, approach of bilateral lesions), with the aim of improving the number of patients undergoing radical excision of all pulmonary metastatic foci. The present paper summarizes a recent experience (1989-1992) in the treatment of pulmonary metastases in 55 patients, with special reference to tactical and technical problems related to metastasectomies. The primary tumor was an osteogenic sarcoma in 28 cases (51%), other musculoskeletal and soft tissue sarcoma in 20 (36%), and epithelial neoplasms in 7 (13%). In 47 patients (85%) the discovery of pulmonary metastases was metachronous regarding primary malignancy, with a range of between 3 months and 17 years; in the other 8, lung disease was simultaneous with diagnosis of neoplasm. All patients underwent preoperative standard chest X-ray, thoracic computerized tomography and lung function assessment; the radical control of primary neoplasm and the absence of any extrapulmonary metastases were required for thoracotomy. Pulmonary nodules were single in 21 patients (38%), multiple ipsilateral in 16 (29) and bilateral in 18 (33%). The thoracic approach was a muscle-sparing thoracotomy (axillary vertical thoracotomy) in 51 patients, other thoracotomies in 3 and a median sternotomy in 1 patient. The operative procedures were 19 single wedge resections (35%), 27 multiple wedge resections (49%), 1 lobectomy (2%), 1 lingulectomy (2%) and finally 7 exploratory thoracotomies (12%) for different reasons. In patients with bilateral disease, a bilateral synchronous thoracotomy and multiple wedge resection was performed 13 times, while staged thoracotomy was necessary in 2 and a median sternotomy was preferred in 1 case; 2 patients received a monolateral axillary exploratory thoracotomy. A total of 186 lung nodules were excised, but only in 161 (86%) the histologic examination confirm the metastasis. There was no operative mortality and the postoperative complications were few. Based on this experience, the authors believe that every neoplastic patient with pulmonary metastases, certain or suspected, should be considered for thoracotomy, since metastasectomy is a very safe procedure today.(ABSTRACT TRUNCATED AT 400 WORDS)

Randomized trial of switching rheumatoid arthritis patients in remission with injectable gold to auranofin.

This prospective unblinded 24-month-study compared the therapeutic value of oral gold with injectable gold to maintain rheumatoid arthritis (RA) patients in clinical remission and prevent the progression of erosive disease. Forty-six patients with definite RA in remission with injectable gold were randomized into two groups: a control group, continued on maintenance injectable gold (Solganal, aurothioglucose, 50-100 mg, intramuscularly, 2 to 4 weeks); and an experimental group, switched to oral gold (6-9 mg auranofin by mouth daily). Only 29% of the original 24 oral gold patients remained on assigned treatment at 24 months compared with 64% of the injectable gold group. By six months, over one-half of the oral gold patients had electively stopped their randomized therapy. Sixty-seven percent of the oral gold patients had adverse reactions, mostly gastrointestinal complaints, compared with one proteinuria in the injectable gold group. The oral gold group experienced significantly more deterioration in all the primary measures of treatment effect over the follow-up period. At the termination of the trial, 88% of the group had increases of 5 or more points in radiographic scores suggesting progression of erosive disease compared with only 29% of the control group. These data suggest that oral gold is not an effective substitute for injectable gold in maintaining remission in rheumatoid arthritis.

Synovial fluid lipoproteins: review of current concepts and new directions.

Recent developments in plasma lipoprotein and apolipoprotein research have been striking, but few studies have focused on the analysis of lipoproteins in synovial fluid (SF). SF contains small amounts of lipoproteins and apolipoproteins. The lipid concentration of normal human SF is extremely low and is in sharp contrast to the concentrations found in plasma. Little is known about the lipids in pathological SF, but studies have noted increased cholesterol and lipoprotein content in rheumatoid arthritis (RA) SF ranging from 40% to 60% of the total plasma lipoproteins. Recently apolipoproteins AI, B and E have also been found to be in increased amounts in RA SF. Several theories have been proposed to account for the increased presence of SF lipids in RA. Animal and human studies indicate the SF cholesterol, lipoproteins, and apolipoproteins may aggravate the inflammatory reaction within the synovial space. Research suggests an immunologic role for plasma lipoproteins on lymphocyte and monocytes in the blood and lymph. SF lipoproteins and apolipoproteins should be studied to define their actions within the synovial space.