Curcumin acts anti-proliferative and pro-apoptotic in human meningiomas.

Meningiomas, the most frequent benign intracranial and intraspinal types of tumors are normally removed by surgery. Complications can occur when the tumor is critically localized and cannot be completely removed or when comorbidities of the mostly elder patients increase the general surgical risk. Thus, alternate medical treatment concepts for the therapy of meningiomas would be desirable. Curcumin, the active ingredient of the spice plant Curcuma longa has shown anti-tumorigenic actions in many different types of tumors and therefore, its effect on growth and apoptosis of meningioma cells was studied in the present paper. In vitro, treatment of the human Ben-Men-1 meningioma cell line and of a series of 21 primary human meningioma cell cultures with curcumin (1-20 µM) strongly reduced the proliferation in all cases in a dose dependent manner. Cell cycle analysis by fluorescence-activated cell sorting showed growth arrest at G2/M phase, which was confirmed by demonstrating the corresponding modulation of proteins involved in G2/M arrest by immunoblotting and/or confocal laser microscopy. High dosages (20, 50 µM) of curcumin induced a significant increase of apoptosis in Ben-Men-1 and primary meningioma cell cultures as demonstrated by morphological changes of cell nuclei, DNA fragmentation, translocation of cell membrane associated phosphatidyl serine and the induction of apoptotic-acting cleaved caspase-3. Our results suggest that the multi-targeting drug curcumin has potent anti-tumorigenic actions in meningioma cells and might therefore be a putative candidate for the pharmacological treatment of meningiomas.

Imbalance between apoptosis and proliferation causes late radiation damage of salivary gland in mouse.

Severe xerostomia is a common late radiation consequence, which occurs after irradiation of head and neck malignancies. The aim of the present study was to analyze apoptosis and proliferation and their relationship during the late post-irradiation phase. C57BL/6 mice were locally irradiated in head and neck region with a single dose of 7.5 or 15 Gy and their submandibular glands were collected at 40 and 90 days after irradiation. To identify apoptotic cells, the TUNEL method was employed and immunohistochemistry with proliferating cell nuclear antigen (PCNA) was used for detecting proliferation. Histological changes at day 40 were mild in contrast to day 90 when glands of irradiated mice showed severe atrophy, vacuolization and mononuclear infiltration. Acinar cells, granular and intercalated duct cells of mice irradiated with 7.5 and 15 Gy expressed higher apoptotic index than cells of non-irradiated, control glands at both examined time points. At 40 days, a higher proliferation index in granular and intercalated duct cells was detected only in group irradiated with 7.5 Gy. At 90 days, proliferation index for all cell types in both irradiated groups was similar to the controls. According to our results, the imbalance between apoptosis and proliferation caused by X-irradiation may be the reason for gland impairment during the late post-irradiation phase.

Thyroid function, metabolic indices and growth performance in pigs fed 00-rapeseed meal.

Thyroid function and morphology, liver morphology, some metabolic indices, haematological parameters and growth performance of fattening pigs fed 00-rapeseed meal (00-RPM) were examined. The control group was fed on a standard diet containing 6% sunflower seed meal (SM) during the growing period and 8% during the finishing period. The first experimental group was fed a diet in which SM was replaced by equal (6% and 8%) amounts of 00-RPM. The second experimental group was fed with a higher (8% and 10%) amount of 00-RPM. There were no significant differences between the control and experimental groups in the serum concentrations of triiodothyronine (T3) and thyroxine (T4). Thyroid gland and liver weights were significantly (P < 0.01) higher in both groups fed 00-RPM than in the group fed SM. The epithelium of the thyroid gland was cuboidal or columnar and the follicular area was moderately enlarged in pigs fed 00-RPM. Marked changes in liver histology were not observed. The 00-RPM diet increased (P < 0.01) the serum values of total proteins in the first fattening period. At the end of fattening both groups fed 00-RPM had higher (P < 0.05; P < 0.01) concentrations of plasma glucose than the control group. The inclusion of 10% of 00-RPM during the finishing period increased (P < 0.05) the serum values of insulin. Daily weight gain during the growing and the finishing period was higher (P < 0.05) in the experimental groups than in the control group. The results suggest that 6-10% 00-RPM can be used as a protein source in the diet of fattening pigs without poisonous side effects.

Influence of rapeseed meal on productivity and health of broiler chicks.

Research was focussed on investigating the influence of different quantities (0, 10, 20 and 30%) of rapeseed meal (RM), 00-cultivar Silvia on production results, as well as on the morphological and pathohistological changes in the internal organs of chicks during the course of the experiment, measured on the 21st and 42nd days of the 42-day experiment. The experiment involved 120 chicks divided into four groups: a control group (C) and three experimental groups (E1-3). It was found that chicks in Groups C, E1 and E2 realised significantly (P < 0.05) higher gains than those in Group E3, both after the test period and at the end of the experiment. No significant differences with regard to feed conversion were found between groups of chicks. Throughout the experiment chicks in Groups E1-3 were found to have a significantly (P < 0.05) heavier liver. Compared to Groups E1-3, Group C chicks had a significantly (P < 0.05) heavier gizzard after 21 days, but following the finisher diet Group E3 had a significantly (P < 0.05) lighter gizzard. Compared with birds in Group C, those in Groups E2-3 had significantly heavier (P < 0.05) unevacuated intestines when fed the starter diet, and those in Groups E1-2 showed a similar result when fed the finisher diet. Chicks in Group E3 had a significantly lower grill weight than those in Groups C, E1 and E2, both in the first half of the experiment and at the end. The starter diet did not result in any differences in the quantity of abdominal fat among groups, but following the finisher diet Groups E2-3 showed significantly less abdominal fat in comparison to Groups C and E1 (P < 0.05). Group C showed a significantly higher carcass yield than Groups E1-3 (P < 0.05) in the first half of the experiment and at the end. Groups E1-3 manifested a slight to medium hypertrophy of thyroid epithelial tissue as well as slight thymus hypertrophy and slight atrophy of the cloacal bursa follicles.

[Anti-U1RNP antibodies and lupus nephritis]. / Anti-U1RNP antitela i lupusni nefritis.

INTRODUCTION: Systemic Lupus Erythematosus is characterized by production of numerous autoantibodies as an abnormal immune response. The most important antibodies are those aimed at constitutive elements of cell nucleus. METHODS: After antigen typing of antinuclear antibodies in 30 patients with Systemic Lupus Erythematosus we analyzed the correlation between anti-Sm antibodies and anti-U1RNP antibodies and the degree of disease activity, such as correlation of these two antibodies with some clinical manifestations of this disease. This study included patients who fulfilled all revised American Rheumatism Association criteria to diagnose systemic lupus. To determine the degree of disease activity we used Systemic Lupus Erythematosus Disease Activity Index after Bombardier. To detect antinuclear antibodies technique of indirect immunofluorescence and ELISA procedure for antigen typing of these antibodies were used. RESULTS: We registered antinuclear antibodies (ANA) in 100% of our patients, with domination of homogenous pattern of immunofluorescence (70%). Speakled pattern was registered in 16.66% and margin type in 6.66%. Using ELISA procedure of antigen typing of ANA we registered anti-U1RNP antibodies in 26.7% patients, while anti-Sm antibodies were registered in 20%. CONCLUSION: Anti-U1RNP antibodies finding is associated with mild forms of disease and rare appearance of lupus nephritis, while anti-Sm antibodies finding is characteristic for very active forms of disease and often lupus nephritis.

Reproductive disturbance caused by an S-triazine herbicide in pigs.

The aim of the study was to assess the effect of subacute treatment with a low dose of atrazine (1,3,5-triazine-2,4-diamine, 6-chloro-N-ethyl-N'-(1-methyl-ethyl), an s-triazine herbicide, on endocrine oestrus regulation in gilts. A group of nine gilts (F1 generation of Swedish Landrace x Large Yorkshire) were treated with 1 mg atrazine/kg body mass daily, mixed to the feed for 19 days before the onset of expected oestrus. Blood samples were obtained by cranial vena cava puncture three times daily at 3-h intervals on five post-treatment days, i.e. before and during oestrus. The serum concentration of oestradiol-17 beta (E2) was determined by the fluoroimmunochemical method. On Day -2 before the onset of expected oestrus, a significantly lower (P < 0.001) E2 concentration was measured in the serum of treated gilts (31.25 +/- 1.95 and 39.32 +/- 1.38 pg/mL) than in the control pigs (51.43 +/- 1.29 and 68.59 +/- 2.99 pg/mL). In contrast, the E2 concentration measured in the serum of treated animals was significantly higher (P < 0.001) on the day of the expected onset of oestrus and on the subsequent two days (35.43 +/- 1.85, 53.92 +/- 1.98 and 60.32 +/- 2.35 pg/mL, respectively) than in the control animals (13.52 +/- 1.79, 21.53 +/- 1.35 and 20.05 +/- 1.46 pg/mL, respectively). Insufficient serum E2 concentration of the treated gilts resulted in a failure of expected oestrus, as indicated also by the state of dioestrus demonstrated by histopathological examination of the uterus.

An outbreak of abortion in mares associated with Salmonella abortusequi infection.

An abortion outbreak occurred in a herd of 38 horses, 26 of which were pregnant mares. Twenty-one mares aborted between 5-10 months of gestation. In no case were there indications of impending abortion. Pathoanatomical, histopathological, virological and bacteriological examinations were carried out on 4 aborted fetuses. Histopathology identified Gram-negative bacteria compatible with salmonella in all 4 placentae. By subsequent bacteriological examination Salmonella abortusequi was isolated as the single causative agent in each case. Nonmotile Salmonella abortusequi with antigenic formula 4,12:-:- was isolated from one of the 4 fetuses. The described episode of equine abortion clearly indicates that Salmonella abortusequi has not been eradicated from Europe as previously thought.

[Psoriatic arthritis: case report of acute HLA-B27 positive polyarthritis preceding the onset of typical skin changes]. / Psoriaticni artritis: povodom slucaja u kome je akutni HLA-B27 pozitivni poliartritis prethodio nastanku tipicnih koznih promena.

Psoriasis usually occurs many years before development of arthritis. This is a case report of a patient with acute polyarthritis affecting both peripheral joints and the left sacroiliac joint, preceding the appearance of typical skin manifestations for almost two months. A 44-year-old male mechanic was admitted to our institution for acute additive polyarthritis. Inflammatory synovitis primarily affected large peripheral joints (knees, ankles) in an asymmetrical pattern, with a concomitant development of unilateral sacroiliitis and later with asymmetrical involvement of several proximal and distal interphalangeal joints of the hands and feet. There were also signs of enthesopathy of the right heel. Arthritis was not proceeded by infection of the lower genital or gastrointestinal tract or serological and bacteriological evidences of streptococcal or HIV infection. Laboratory findings showed an erythrocyte sedimentation rate (92 in the first hour), positive histocompatibility antigen HLA-B27 and an increased level of acute phase reactants. Almost two months after affecting the locomotor system a typical psoriatic rash developed, first affecting the scalp and then spreading over the trunk and extremities. It was accompanied by severe onychodystrophy. The patient underwent intensive treatment with methylprednisolone (1.5 mg/kg) and cyclosporine A with significant results.

Serum biochemical changes associated with cystic ovarian degeneration in pigs after atrazine treatment.

Biochemical and histopathological parameters of the ovarian function were observed to assess the toxic effect of low dose of atrazine, an s-triazine herbicide, in female pigs (gilts) undergoing intensive breeding. Female pigs (cross-bred between Swedish and German landrace) received 2 mg atrazine kg-1 body wt. in feed daily during 19 days of the oestrous cycle. The last treatment day corresponded to day -3 of the onset of the next expected oestrus. Blood samples were collected 3 times daily at 3-h intervals on the first 5 post-treatment days. Serum 17 beta-oestradiol (17 beta-E) and progesterone (P) concentrations were determined. A significantly higher (P < 0.05 and P < 0.001, respectively) serum 17 beta-E concentration was recorded 48 and 24 h before the onset of the next expected oestrus in atrazine-treated pigs, as compared to intact pigs. The onset of the next expected oestrus failed to occur, but no other adverse clinical reactions associated with the treatment were recorded. Histopathological examination of the ovaries of treated pigs indicated multiple ovarian follicular cysts and persistence of corpus luteum. Biochemical and histopathological findings showed that subacute exposure of female pigs to low dose of atrazine prolonged their oestrous cycle.

[Results of a multi-year study of persons with transplanted kidneys]. / Rezultati visegodisnjeg ispitivanja osoba s transplantisanim bubregom.

The authors review their results of five year follow up of renal transplantation. They summarised the results of treatment with three immunosuppressive regimens. There is an analysis of rejection episodes, recurrent glomerulonephritis, infections, surgical complications, a median graft as well as patient survival and other patterns of complications of renal transplantation.

[Urinary infections in patients with transplanted kidneys]. / Urinarne infekcije kod bolesnika s transplantisanim bubregom.

The aim of this study was to evaluate urinary infection frequency in kidney transplanted patients. Infection frequency was assessed in 116 patients (81 males and 35 females; mean age 36.2 years) after renal transplantation. During four year follow-up 41% patients suffered one or more episodes of infection. Bacterial infection caused by Escherichia coli were most frequent. The control group consisted of healthy medical staff and the investigations showed significantly over frequency of infection.

[Methylprednisolone pulse therapy in the early phases of lupus nephritis]. / Dejstvo pulsne terapije metilprednozolonom kod ranih faza lupusnog nefritisa.

Renal involvement i.e. lupus nephritis (LN) in systemic lupus erythematosus (SLE) mainly determines course and outcome of the disease. Recognition of early manifestations of LN makes adequate therapy possible, with very good therapeutic results. We report 7 patients from a group of 150 SLE patients under our permanent control, 4 female and 3 male, mean age 21 years. All of them had signs of LN: proteinuria 7/7 haematuria 4/7 without azotaemia. Renal biopsy was performed in 6 pts, and histological finding was: class II 1 pt, class IV 3 pts and class V in 2 pts. In 4 pts tubulointerstitial changes were noted, while all showed immunofluorescent deposits of immunoglobulins and complement. Methylprednisolone "pulse" therapy (1000 mg, i.v., 3 days) followed by tapering of the steroid dose was given. Reduction of proteinuria and disappearance of haematuria were observed in all patients. During follow up, kidney function remained normal.

Serum biochemical and histopathological changes related to the hepatic function in pigs following atrazine treatment.

Biochemical and histopathological parameters of the hepatic function were used to quantify the hepatotoxic effects of atrazine in female pigs (gilts) undergoing intensive breeding. Female pigs (cross-bred Swedish and German landrace) received 2 mg atrazine kg-1 body wt. in feed daily during 19 days of the oestrous cycle. The last treatment day corresponded to day -3 of the onset of the next expected oestrus. Blood samples were collected three times daily at 3-h intervals on the first four post-treatment days. Serum activities of gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP) were determined. Serum activity of GGT was significantly increased throughout the four post-treatment days. In comparison with the control values, a slight but not significant decrease was observed in the serum activities of ALT, AST and AP. Histopathological examination of the liver of exposed pigs showed mild centrolobular parenchymatous degeneration. Interstitial connective tissue proliferation resulted in narrow and irregular bile canaliculi.

Histopathological features in the small intestine of pigs infected with F4ac+ non-enterotoxigenic or enterotoxigenic strains of Escherichia coli.

Four porcine strains of Escherichia coli were examined for their effects on the small intestine of 4-week-old weaned pigs infected orogastrically. The strains used experimentally were: strain 1467 (adhesin negative, non-toxigenic); strains 2407 and 1466 (adhesin positive, non-toxigenic), derived by genetical engineering from strain 1467 and containing a wild type plasmid and a recombinant plasmid, respectively, encoding the F4 antigen (adhesin); and strain M1823 (adhesin positive, toxigenic). In addition, 2-week-old pigs that died from natural colibacillosis associated with two strains ("Ihan 1 and 2"; adhesin positive, toxigenic) were examined. Strain M1823 and the Ihan strains produced moderate and marked lesions, respectively. Strain 1467 did not cause mucosal damage or an inflammatory response. Strains 1466 and 2407 caused a mild to moderate leucocyte (mononuclear and polymorphonuclear) infiltration in the jejunal (but not ileal) lamina propria. However, unlike strain 1466, strain 2407 did not cause damage to the small intestinal mucosa and should be further studied as a potential oral vaccine strain for post-weaning E. coli diarrhoea.

[Anti-proteinuria effects of nonsteroidal anti-inflammatory drugs in patients with nephrotic syndrome: an illusion or a read improvement?]. / Antiproteinuricni efekat nesteroidnih antiinflamacionih lekova u bolesnika s nefrotskim sindromom: privid ili stvarno poboljsanje?

In order to examine the antiproteinuric effect of non-steroidal antiinflammatory drugs in patients with nephrotic syndrome, we performed a parallel determination of the daily proteinuria, strength of glomerular filtration and of the effective renal plasmatic flow in basal conditions and after a 7 day ibuprofen therapy at a daily dose of 1200mg (3 x 400mg) in a group of 12 patients with idiopathic glomerulonephritis. In all patients ibuprofen therapy induced a significant decrease of the existing proteinuria, but this decrease was accompanied by the decrease of clearance rate of 99mTc-DTPA and 131J-hipuran clearance, that is by decrease of strength of glomerular filtration (averagely 24.29%) and effective renal plasmatic flow (averagely 18.74%). It can be concluded that the decrease of proteinuria in patients with nephrotic syndrome after ibuprofen therapy (as well as other non-steroidal antiinflammatory drugs) is primarily the result of worsening of hemodynamic conditions in the kidney, that it is caused by the reduction of the renal blood flow and by the strength of glomerular filtration in conditions of cycloxygenetic activity inhibition in the kidney.

Ferruginous bodies in the lungs of urban dogs.

The aim of the study was to assess health hazards induced by environmental exposure to asbestos using urban dogs as biological indicators. Samples of the lung tissue taken from 36 randomly chosen urban dogs were examined. In the group of dogs aged up to four years (n = 15) ferruginous bodies were identified in only two. In the dogs older than four years (n = 21) 17 were ferruginous body positive. According to Fisher's exact test the difference between the two groups was significant (P < 0.001). The presence of asbestos bodies in the lungs of dogs is considered to be evidence of serious contamination of urban areas with respirable mineral fibres. The more frequent presence of asbestos bodies in the lungs of the older dogs indicates long-term accumulation of mineral fibres exceeding 10 microns in length. Continuous environmental exposure of the city's population to respirable mineral fibres may therefore pose a health risk.

Effects of nonsteroidal antiinflammatory drugs on renal plasma flow and glomerular filtration rate in patients with glomerulonephritis.

We investigated the effects of NSAIDs (Ibuprofen) on renal plasma flow (RPF) and glomerular filtration rate (GFR) in patients with glomerulonephritis. The study included 98 patients (53 men and 45 women) with idiopathic glomerulonephritis. All of the patients received Ibuprofen 1200 mg (3x400) during 7 days. Before and after the treatment with Ibuprofen ERPF (clearance of 131I-Hippuran) and GFR (clearance of 99mTc-DTPA) were determined. In our patients administration of Ibuprofen was associated with a significant reduction in renal plasma flow and glomerular filtration rate. In patients with reduced renal function the decrease in RPF and GFR after Ibuprofen was significantly greater than in patients with normal renal function.

[The effect of angiotensin I converting enzyme inhibitors on renal function indicators in hypertensive patients]. / Uticaj inhibitora konvertujuceg enzima angiotenzina-I na funkcijske pokazatelje bubrega u hipertenzivnih bolesnika.

The paper reviews the results of a preliminary study on hemodynamic and functional kidney indices in patients with hypertension with different etiopathogenesis. The investigation was carried out in 36 patients; 30 cases with no renal artery stenosis (RAS) and 6 cases with different stages of RAS. The investigation was conducted both in basal conditions and after the peroral administration of captopril (Zorcaptil à 25 mg, 1h before the examination). Kidney hemodynamics and its function were investigated by the dynamic kidney scintigraphy with the deconvolution analysis of the renogram and by the determination of the total and separate clearances 99Tcm-MAG3 and/or 99Tcm-DTPA. The obtained results lead to the conclusion that the sensitivity of the applied methodology enables differentiation of hypertensions in whose etiopathogenesis the renin-angiotensin-aldosterone system (RAAS) does not play the key role. Further investigations are needed for valid conclusions to be made.

[Immunologic characterization of autoreactivity to nuclear antigens in patients with systemic lupus erythematosus]. / Imunoloska karakterizacija autoreaktivnosti prema nuklearnim antigenima u bolesnika sa sistemskim eritemskim lupusom.

Abnormal immune reactivity, with a production of multiple autoantibodies specially against the components of a nucleoplasm is one of the hallmarks of systemic lupus erythematosus (SLE). Our investigations were conducted on 102 patients with SLE, classified according to the criteria of ARA, aiming to better characterize the overall incidence of anti-nuclear antibodies in SLE, to determine the type of immunofluorescent staining of the nuclei, and to characterize the fine specificity of such antibodies using modified ELISA procedure. Results of our investigation show that 95% of patients with SLE have detectable anti-nuclear antibodies. Predominant pattern of nuclear staining is homogeneous, followed by a speckled type, while the rim (peripheral) pattern is relatively infrequent. Anti-nuclear antibodies showed the highest reactivity against native DNA (70% of patients), which was followed by binding to SS-A, eRNP and SS-B antigens. Interestingly, using ELISA procedure we could observe the reactivity against Sm antigen only in 5% of SLE patients. In patients who showed homogeneous or rim pattern of nuclear staining the predominant type of reactivity was against native DNA, while in patients with speckled type most frequent binding to non-histone proteins was observed. The most frequently observed individual pattern of ANA reactivity was of polyreactive type.