Targeting Tumor Markers with Antisense Peptides: An Example of Human Prostate Specific Antigen.

The purpose of this paper was to outline the development of short peptide targeting of the human prostate specific antigen (hPSA), and to evaluate its effectiveness in staining PSA in human prostate cancer tissue. The targeting of the hPSA antigen by means of antisense peptide AVRDKVG was designed according to a three-step method involving: 1. The selection of the molecular target (hPSA epitope), 2. the modeling of an antisense peptide (paratope) based on the epitope sequence, and 3. the spectroscopic evaluation of sense-antisense peptide binding. We then modified standard hPSA immunohistochemical staining practice by using a biotinylated antisense peptide instead of the standard monoclonal antibody and compared the results of both procedures. Immunochemical testing on human tissue showed the applicability of the antisense peptide technology to human molecular targets. This methodology represents a new approach to deriving peptide ligands and potential lead compounds for the development of novel diagnostic substances, biopharmaceuticals and vaccines.

[BONE MINERAL DENSITY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS--OUR RESULTS]. / POREMECAJ KOSTANE MASE U BOLESNIKA SA SISTEMSKIM ERITEMSKIM LUPUSOM--PRIKAZ VLASTITIH REZULTATA.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing low bone mass (LBM) or osteoporosis, either because of the disease itself or due to its treatment. Osteoporosis and osteoporotic fractures significantly contribute to morbidity and mortality. We aimed to determine the associations of bone mineral density (BMD) changes with the duration of SLE, age, gender, and glucocorticoid treatment in SLE patients treated at our Department. PATIENTS AND METHODS: BMD measurements of the lumbar spine and total hip were performed by dual-energy X-ray absorptiometry (DXA). Osteoporosis and LBM were determined according to the 1994 World Health Organization definition. In the statistical analysis, the independent Mann-Whitney U test and Tukey post-hoc testing were used. RESULTS: The study included 48 SLE patients (44 female and 4 male), with a mean age of 45.8 years and an average SLE duration of 9.8 years. Osteoporosis was diagnosed in 21%, and LBM in 15% of the patients. The mean ages of the subgroups with normal BMD, LBM, and osteoporosis were 41.1, 47.6, and 59.0 years, respectively. Variant analysis showed a statistically significant correlation between age and BMD (p < 0.05). The duration of SLE was significantly shorter in patients with normal BMD (7.3 years), compared to patients with LBM (16.1 years) and osteoporosis (12.9 years) (p < 0.05). Nearly all patients (47 of 48) were on long-term treatment with glucocorticoids. One third (33.3 %) of patients did not take vitamin D3, and 56.3 % did not take calcium supplements. CONCLUSION: The etiopathogenesis of decreased BMD in SLE patients is multifactorial and includes both traditional and SLE-related risk factors. In our group of SLE patients age and glucocorticoid treatment were the major risk factors for LBM. Timely prevention and treatment of LBM and osteoporosis in SLE patients, according to current knowledge, are essential for reducing morbidity and mortality.

Etiology and epidemiology of obstructive jaundice in Continental Croatia.

The etiology and epidemiology of obstructive jaundice in Continental Croatia has been studied in 174 patients. The objective of this research was also to explore the importance and efficiency of endoscopic retrograde cholangiopancreatography (ERCP) as a non-surgical method of treatment of obstructive jaundice in the population of Continental Croatia. Obstructive jaundice is the illness of elderly population which is also confirmed by the information on the average age of our patients. The frequency of illness is higher among female population, and the most frequent cause of obstructive jaundice are gallstones (54.1% of patients). In 29.8% of patients the primary or secondary malignant disease was the cause of blockage in gall flow and subsequent jaundice, and the most frequent malignant cause of obstructive jaundice is pancreas cancer in 11.5% of patients. The mean value of serum concentrations of total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and gamma glutamiltransferase 24 hours before the biliary decompression by ERCP has been significantly above the upper referential value, and 24 hours after the ERCP it has dropped to normal with their statistically significant difference (p < 0.0001). The normal values of markers for synthetic liver function (total proteins and prothrombin time) have been noticed as well as elevated values of inflammatory markers in obstructive jaundice independently of etiology. Out of the total number of patients, 37.7% required the surgical treatment while 60.3% of patients were treated by ERCP, i.e. either the stone extraction or the implantation of endobiliary stent was performed.

[Large vessel vasculitides]. / Vaskulitisi velikih krvnih zila.

Large vessel vasculitis includes Giant cell arteritis and Takayasu arteritis. Giant cell arteritis is the most common form of vasculitis affect patients aged 50 years or over. The diagnosis should be considered in older patients who present with new onset of headache, visual disturbance, polymyalgia rheumatica and/or fever unknown cause. Glucocorticoides remain the cornerstone of therapy. Takayasu arteritis is a chronic panarteritis of the aorta ant its major branches presenting commonly in young ages. Although all large arteries can be affected, the aorta, subclavian and carotid arteries are most commonly involved. The most common symptoms included upper extremity claudication, hypertension, pain over the carotid arteries (carotidynia), dizziness and visual disturbances. Early diagnosis and treatment has improved the outcome in patients with TA.

Clinical efficacy and safety of adalimumab versus etanercept in patients with ankylosing spondylitis and total spinal ankylosis in Croatia: a multicentre 12-month follow-up study.

OBJECTIVE: To evaluate the 12-month efficacy and safety profile of adalimumab and etanercept in patients with ankylosing spondylitis (AS) and total spinal ankylosis (TSA). TYPE OF STUDY DESIGN: Case-series follow-up study. DESIGN: Twenty-eight patients (26 men and 2 women) with active AS (BASDAI > 4) and TSA were treated as follows: 19 patients receiving adalimumab and 9 patients receiving etanercept. Twelve-month data related to the efficacy and safety of these two TNF-alpha inhibitors were evaluated. The primary endpoint was ASAS 20 (the ASsessment in AS International Working Group criteria for 20% improvement) at weeks 12 and 52. Other measures that were evaluated were function (BASFI), disease activity (BASDAI), patient's and physician's global disease assessment on visual analogue scale (VAS) and C-reactive protein. RESULTS: In both adalimumab and etanercept groups, there was a significant improvement in all observed variables (baseline compared to weeks 12 and 52). This improvement was sustained for the whole follow-up period. In the adalimumab group, at week 12, ASAS 20 was achieved in 18/19 patients and at week 52 in 17/19 patients. In the etanercept group, at week 12 ASAS 20 was achieved in all patients and at week 52 in 6/9 patients. CONCLUSION: In patients with active AS and TSA, adalimumab and etanercept treatment showed significant improvement in function and disease activity. No serious side effects or adverse effects were observed in our cohort. Key Points • TNF-alpha inhibitors can be effective treatment options for patients with AS and having total spinal ankylosis. • Patients with advanced AS should not be disregarded as good candidates for treatment with biologic disease-modifying antirheumatic drugs.

Magnetic resonance imaging in the diagnosis and follow-up of giant cell arteritis: case report and review of literature.

A female patient with giant cell vasculitis of the abdominal aorta and its branches and strongly suspected of having extrapulmonary tuberculosis is presented. The diagnoses were based on the clinical picture, laboratory findings, and magnetic resonance imaging (MRI) findings. MRI is highly useful in cases where echosonography and/or vascular biopsy for histopathological analyses are not possible. A combination of giant cell vasculitis and extrapulmonary tuberculosis is extremely rare, and therefore, choosing the right treatment presents a considerable challenge. MRI performed after 6-month antituberculous therapy and 1-year glucocorticoid plus methotrexate therapy showed normal wall of the aorta and its branches, which was consistent with clinical and laboratory remission. Patients with large vessel vasculitis require regular follow-up by MRI.