Effect of raloxifene on lowering lipid parameters in patients with osteoporosis.

The aim of this study was to show the effect of raloxifene on the lowering of lipid parameters in patients with osteoporosis. New investigations introduced selective estrogen receptor modulators (SERMs), such as raloxifene, as a potent drug in the lowering of lipid parameters. Raloxifene is known as a substance that works well in preventing and treating osteoporosis. We investigated the effect of raloxifene on the lowering of lipid parameters (cholesterol and triglycerides) in 94 women who took 60 mg/day of raloxifene for the treatment of osteoporosis. We performed three measurements of cholesterol and triglycerides, at the beginning of the study and at 3 and 12 months. Bone mineral density (BMD) was measured at the begining and at 12 months; spine BMD increased 2.7%. The mean value of cholesterol was 6.6961 mmol/l at the beginning, 6.060 mmol/l at 3 months and 5.826 mmol/l at 12 months. The difference between mean values was statistically significant at p < 0.01. Mean values of triglycerides were 2.153 mmol/l at the beginning, 1.970 mmol/l at 3 months and 1.680 mmol/l at 12 months. The difference between mean values at 3 months was statistically significant at p < 0.05 and at 12 months at p < 0.01. We concluded that raloxifene had significant effects on lowering cholesterol and triglycerides in postmenopausal women and that raloxifene is the best choice in the treatment of osteoporosis and moderate lipid disorders.

Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone.

Recently, we showed cysteamine-duodenal lesions without gastric acid, since they were induced also in gastrectomized rats, as in naive rats, and they were inhibited by the novel stomach pentadecapeptide BPC 157 as well as standard antiulcer drugs (i.e. cimetidine, ranitidine, omeprazole, bromocriptine, atropine). Therefore, as an advantage of considering cysteamine as a directly acting cytotoxic agent and mentioned agents as direct cytoprotective agents, the present focus was on the ulcerogenic effect of cysteamine and protective effect of gastroduodenal antiulcer agents outside upper gastrointestinal tract (i.e. in colon). Intrarectal administration of the cysteamine (200 or 400 mg/kg b.w) produced severe colon lesions (i.e. transmural inflammation with serosal involvement) in rats (30 min-72 h-experimental period), apparently distinctive from smaller lesions after non-specific irritant enema [diluted HCl solution, pH 3.8 (adjusted to pH of cysteamine solution (pH 3.8)]. All of the tested antiulcer agents were applied simultaneously with cysteamine enema (8 cm from the anus, in a volume of the 1.0 ml/rat) intraperitoneally (i.p.), intragastrically (i.g.) or intrarectally (i.r.). Pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w.), given in either regimen, previously shown to have, besides others, a particular beneficial activity just in the intestinal mucosa, inhibited these cysteamine colon lesions (assessed after 30 min, 60 min, 180 min, 24 h, 48 h, 72 h following cysteamine in a dose of either 200 or 400 mg/kg i.r.). Cysteamine-colon lesions were also attenuated by standard antiulcer agents (mg/kg b.w.), given i.p., i.g., or i.r., such as ranitidine (10), cimetidine (50), omeprazole (10), atropine (10), together with methylprednisolone (1), and sulphasalazine (50, i.r.), assessed 30 min following application of 200 mg of cysteamine. Finally, standard cysteamine duodenal lesions (assessed 24 h after a subcutaneous application of 400 mg/kg of cysteamine) were also attenuated by these agents application (given in the same doses, i.p., 1 h before cysteamine), with only exception to sulphasalazine. Thus, the extended cysteamine specific ulcerogenic effect, cysteamine colon/duodenum lesion-link and an extenuation of agents protection from upper to lower part of gastrointestinal tract (i.e. stomach pentadecapeptide BPC 157, standard antiulcer agents, cimetidine, ranitidine, atropine, omeprazole) and vice versa (remedies for inflammatory bowel disease) evidenced in the present study may be potentially important for both further experimental and clinical research.

Therapy effect of antiulcer agents on new chronic cysteamine colon lesion in rat.

After demonstration that cysteamine induced duodenal lesions in gastrectomized rats, while a number of antiulcer drugs mitigated these lesions, it was shown that one single intrarectal (i.r.) cysteamine application produced severe colon lesions in acute studies in rats. Thus, the further focus was on the protracted effect of cysteamine challenge (400 mg/kg b.w. i.r.) and therapy influence in chronic experiments in female rats. Regularly, cysteamine colon lesions were markedly mitigated by ranitidine (10), omeprazole (10), atropine (10), methylprednisolone (1), sulphasalazine (50; mg/kg), pentadecapeptide BPC 157 (PL-10, PLD-116; 10 microg or 10 ng/kg). Specifically, after 1 or 3 months following initial challenge (cysteamine 400 mg/kg i.r.) in female rat, the therapy [BPC 157 (PL-10, PLD-116 (10.0 microg or 10.0 ng/kg; i.g., i.p., i.r.), ranitidine, omeprazole, atropine, methylprednisolone, sulphasalazine (i.p.)] reversed the protracted cysteamine colon injury: the 1 week-regimen (once daily application) started after 1 month post-cysteamine, as well as the 2 weeks-regimen (once daily application), which started after 3 months. The effect on recidive lesion was also tested. These cysteamine lesions may reappear after stopping therapy (after stopping therapy for 3 weeks at the end of 2-weeks regimen started in 3 months-cysteamine female rats) in sulphasalazine group, while this reappearance is markedly antagonized in pentadecapeptide BPC 157 (PL-10, PLD-116)-rats (cysteamine-colon lesion still substantially low).

The hundredth anniversary of the Slavonski Brod Hospital.

In 1998, Dr. Josip Bencevic General Hospital in Slavonski Brod celebrated 100 years of its work. The first Hospital building started working on April 1, 1898. At present, the Hospital has 650 beds, 1240 employees, 210 of them with university degree, most of them physicians and some other professionals, and about 550 nurses. All medical specializations have been developed, while an appropriate level of equipment ranks this medical institution high among county hospitals in Croatia.

Organization and work of medical service during 1992 military operations in north Bosnia (Bosanska Posavina).

During military operations in Bosanska Posavina in 1992, 6,105 soldiers of the army of the Croatian Defence Council (Bosnian Croats and Muslims) were treated at various health care levels: 920 soldiers were killed, 3,258 were heavily wounded, and 1,927 lightly wounded. The treatment was provided in medical units organized on the front line, in the combat area, and in the communication area. On the front line, medical service was organized as battalion units, whereas the area in general was medically covered by the Slavonski Brod Medical Center in Croatia. Slavonski Brod played a key role with surgical treatment of 5,418 wounded, and definitive care was offered to most subjects seeking medical aid. Scarcity of medical personnel on the front lines and long lines of transportation resulted in a 6.5% death rate (354 patients) during transportation from Bosnian battlefields to Slavonski Brod. In contrast, the mortality rate in the Slavonski Brod Hospital was 3.0% (161 patients). Convalescence homes were established in the Slavonski Brod surroundings, whereas specialized health institutions and rehabilitation centers throughout Croatia accommodated those needing advanced treatment.

Work of the Slavonski Brod General Hospital during the war in Croatia and Bosnia and Herzegovina in 1991-1992.

Between September 1, 1991, and December 31, 1992, 7,043 wounded persons, 4,566 of them heavily wounded, were treated at the Slavonski Brod General Hospital. There were three characteristic periods in the work of the hospital during the war. Until March 31, 1992, the hospital provided care for the wounded from the east- and west-Slavonian fronts, at the level of the fourth echelon. The second period started with war actions in Bosanska Posavina and Bosnia and Herzegovina, when the Slavonski Brod General Hospital was the only place offering appropriate care to the wounded from the area. During that period, surgical professions and, to a limited extent, conservative professions were working at the hospital. The third period began with the fall of Bosanska Posavina, toward the end of October 1992, and lasted until the end of the year. During that period, the number of the wounded and previously surgically treated at the Tolisa War Hospital, in the unoccupied area of Bosnia and Herzegovina, admitted to the Slavonski Brod General Hospital, decreased. The total mortality rate in the treated subjects was 2.66%, whereas during the war in Bosanska Posavina it was 3.0%. Throughout the war, there was no interruption in the work of hospital conservative professions, although the extent of their work was reduced.

Prevalence of markers of hepatitis B virus infection among the general population of the municipality of Slavonski Brod.

To assess the prevalence of hepatitis B viral infection in general population of the Community of Slavonski Brod, sera from 2,142 apparently healthy individuals were tested for the hepatitis B virus (HBV) markers: surface antigen and antibody (HBsAg and anti-HBs), and core antibody (anti-HBc), by radio and enzyme-immunoassay. The HBsAg results showed a general prevalence of 1.8%(38/2,142): for males 1.9% and for females 1.6%. The highest HBsAg incidence rates (2.1% and 1.9%) were found in young adults aged 21-30, respective in older children and adolescents, from 11 to 20 years. The lowest HBsAg prevalence (1.0%) was proved in children from 1 to 5 years, while in sera of 68 examined sucklings HBsAg was not detected. The HBsAg incidence was 1.9% (21/1132) in urban and 1.7% (17/1010) in rural inhabitants. The overall prevalence rate of total HBV infection in 13.7% (294/2,142) examinees was found. There was no difference in the prevalence of HBV infection in males 15.7% (177/1130) and females 11.6% (117/1012), as well as in persons living in rural 12.5% (126/1010) or in urban 14.8% (168/1132) areas. The prevalence rate of anti-HBs and anti-HBc gradually increased with increasing age, starting at about 3.2% in the youngest, and reaching 15.5% in adults over 50 years. The results obtained have place the Community of Slavonski Brod among areas with an intermediate endemicity of HBV infection.

In rat B lymphocyte genesis sixty percent is lost from the bone marrow at the transition of nondividing pre-B cell to sIgM+ B lymphocyte, the stage of Ig light chain gene expression.

The cycling B precursor cells in rat bone marrow (BM) that carry the B220 antigen and no surface Ig daily produce 780 million new cells. The pool of recirculating B lymphocytes in the rat, however, renew at a rate of only about 40 million cells/day. To analyze at which stages in B lymphocyte genesis the cell loss occurs, we identified post-mitotic cells in the rat BM B lineage, and determined their renewal rates. We used 5-bromo-deoxyuridine (BrdUrd) to label DNA-synthesizing cells, identifying incorporated BrdUrd with the mouse monoclonal antibody BU-1. B lineage cell subsets were identified by the markers HIS24 antigen (rat B220), terminal deoxynucleotidyl transferase (TdT), Ig mu heavy chain, and complete Ig. By use of double and triple immunocytology, we determined the extent of BrdUrd incorporation in the various B lineage compartments [HIS24+TdT-Ig-, TdT+, cytoplasmic mu chain (c mu)+ surface (s) IgM- pre-B, sIgM+ B]. Both sIgM+ B lymphocytes and all B precursors with cell diameters less than 11-12 microns were virtually devoid of DNA synthesis, as indicated by S-phase indices below 2%. In contrast, S-phase indices of large B precursors ranged between 43%-66%. We established the renewal rates of nondividing BM B lineage cells by placing osmotic minipumps containing BrdUrd subcutaneously in the flank of rats. The nondividing BM B lineage cells all renewed rapidly at rates between 2.4% and 5.6%/h, representing average half-lives of 29 to 12 h. In absolute numbers, the renewal/day/whole body BM was 165 X 10(6) for sIgM+ B lymphocytes, 422 X 10(6) for small c mu+ sIgM- pre-B cells, 89 X 10(6) for small TdT+ cells and 35 X 10(6) for small HIS24+TdT-Ig- cells. Assuming that recirculating B lymphocytes in the periphery are the descendants of BM sIgM+ B lymphocytes, which in their turn are the progeny of small pre-B cells, the renewal data indicate the following. Of the 165 million potentially available BM B lymphocytes, only 40 million cells become incorporated in the pool of recirculating B lymphocytes, representing a loss of 75%. BM B lymphocytes, in turn, use only (165/422 X 100% = ) 40% of the potential output from their immediate precursors. The 60% loss that occurs here may reflect the extent of aberrant Ig light chain gene rearrangement in normal B lymphocyte genesis.(ABSTRACT TRUNCATED AT 400 WORDS)

An inherited restriction in the idiotypic variability as a possible explanation of a genetic predisposition for a monoclonal component.

Genetic factors have been proposed to play a role in the aetiology of a monoclonal proliferation of B lymphocytes. As an additional genetic factor we postulate that a restriction in the idiotypic variability of an individual contributes to a genetic predisposition to monoclonal gammopathy. To support our hypothesis, we have examined three families with multiple occurrence of M-components for sharing of idiotypic antigenicity between the related M-components and between the M-components and the sera of unaffected relatives. Idiotypic antisera against five isolated M-components were raised in guinea-pigs and used in a radiobinding inhibition assay. In none of the three families was idiotypic cross-reactivity observed between the familial M-components. However, in a family with three members with an M-component, sera of first-degree relatives showed a higher inhibitory capacity than sera of non-related individuals when an idiotypic antiserum, raised against the M-component of proposita, was employed. Within this particular family the observed restriction in the idiotypic variability could have contributed to the multiple occurrence of M-components.