Molecular heterogeneity of somatostatin analogue BIM-23014C receptors in human breast carcinoma cells using the chemical cross-linking assay.

Distinct proteins complexed with somatostatin and the somatostatin analogue BIM-23014C were revealed in human breast cancer cells using the cross-linking assay. One BIM-23014C-specific complex (Mr 57,000) was observed in MCF-7 (monolayer, nodule, and tumor) and T47D. Growth inhibition of MCF-7 tumor xenografts by BIM-23014C was dose related in the 6-day subrenal capsule assay. Three complexes (Mr 27,000, 42,000, and 57,000) were detected in MDA-MB-231, and no complex was visible in HBL-100. No correlation was found between receptors for BIM-23014C and epidermal growth factor in these lines. Twenty-seven of 30 human breast tumors (90%) had at least one BIM-23014C receptor. Sixteen had three complexes (Mr 27,000, 42,000, and 57,000). Six had the two complexes (Mr 27,000 and 57,000), two had Mr 42,000 and 57,000 complexes, two had just the Mr 27,000 complex, and one had just the Mr 42,000 complex. The presence of the three BIM-23014C receptors was positively correlated (P less than 0.05) to the low amount of sex steroid receptors (less than 20 fmol/mg) [seven of eight (estrogen receptor negative, progesterone receptor negative) versus four of 14 (estrogen receptor positive, progesterone receptor positive)]. Another positive correlation was established between the absence of progesterone receptors and the presence of these three complexes [12 of 16 (progesterone receptor negative) versus four of 14 (progesterone receptor positive)]. This high percentage of BIM-23014C receptor-positive biopsies and its inhibitory activity would support its clinical potential for the treatment of breast cancer.     

Tissue engineering of bone for mandibular augmentation in immunocompetent minipigs: preliminary study.

Large mandibular defects caused by trauma, infection or resection of a tumour are still a major problem for plastic and maxillofacial surgeons. The modern concept of tissue engineering combines the osteoinductive effects of osteogenic cells with a suitable scaffold structure to promote differentiation of osteoblasts and optimal matrix production. Critical size mandibular bone defects were therefore made to investigate the osteogenic potential of periosteal cells and a bioabsorbable polymer fleece (Ethisorb 510) in minipigs. Periosteal cells were isolated from four minipigs, expanded in vitro and seeded with fibrin glue into Ethisorb 510 fleeces. Tissue constructs were used to repair critical size mandibular defects and compared with two minipigs with untreated bone defects. Bone healing was evaluated after 90 and 180 days by radiographs and a histological scoring system. The radiographs showed increased radiodensity of defects filled with the cell-fibrin-fleece-constructs compared with the untreated control group after 90 and 180 days in vivo. The defects repaired by the cell-fibrin-scaffolds (180 days in vivo) obtained the highest histological mean score 2.9 (range 2-3), while defects filled by cell-fibrin-scaffolds (90 days in vivo) achieved a mean score of 2.1 (range 2-3). In contrast, the control group (n = 2) scored 1 and 2. The results show that a combination of periosteal cells and polymer fleeces may be a promising approach for clinical mandibular augmentation.     

Evaluation of plantar hyperhidrosis in patients undergoing video-assisted thoracoscopic sympathectomy

Background Sympathectomy is the treatment of choice for primary hyperhidrosis. One curious occurrence that is difficult to explain from an anatomophysiological point of view in cases of video-assisted thoracoscopic sympathectomy (VATS) for the treatment of palmar hyperhidrosis (PH) is the observed improvement in plantar hyperhidrosis (PLH). Nevertheless, current reports on VATS rarely describe the effect on PLH or just give superficial data. The aim of this study was to prospectively investigate, how surgery affects PLH in patients with PH and PLH over one-year period. Methods From May 2003 to January 2004, 70 consecutive patients with combined PH and PLH underwent VATS at the T2, T3, or T4 ganglion level (47 women and 23 men, with mean age of 23 years). Results Immediately after the operation, all the patients said they were free from PH episodes, except for two patients (2.8%) who suffered from continued PH. Compensatory hyperhidrosis (CH) of various degrees was observed in 58 (90.6%) patients after one year. Only 13 (20.3%) suffered from severe CH. There was a great initial improvement in PLH in 50% of the cases, followed by progressive regression, such that only 23.4% still presented that improvement after one year. The number of cases without overall improvement increased progressively (from 17.1% to 37.5%) and the numbers with slight improvement remained stable (32.9–39.1%). Of the 24 patients with no improvement after one year, 6 patients graded plantar sweating worse. Conclusion Patients with PH and PLH who undergo VATS to treat their PH present a good initial improvement in PLH that reduces to a lower level of improvement after the one-year period.     

Laboratory investigation: Effects of propofol on the systemic inflammatory response during aortic surgery

PURPOSE: A laboratory investigation was undertaken to assess the effects of propofol on renal function, through modulation of the systemic inflammatory response, in an in vivo experimental model of aortic surgery in comparison with sevoflurane. METHODS: Twenty young male piglets were anesthetized with either propofol 4 mg.kg(-1).hr(-1) (n = 10) or sevoflurane 1.5% end-tidal concentration (n = 10). Animals were subjected to aorta-aortic bypass with suprarenal aortic clamping for 30 min. At specific intervals (basal -before the start of surgery; reperfusion 15 min after unclamping the aorta; at 24, 48 and 72 hr after surgery, and on the seventh day after surgery) the levels of the following were determined: plasma creatinine, renal myeloperoxidase, tumour necrosis factor-alpha, interleukin 1-ss, and interferon-gamma; kidney superoxide anion and its detoxifying enzyme superoxidase dismutase, kidney malondialdehyde and the activity of inducible nitric oxide synthase. Seven days after surgery, the animals were anesthetized using the described techniques, and after blood withdrawal and kidney sampling they were sacrificed. RESULTS: In comparison with sevoflurane, propofol was associated with a lower concentration of plasma creatinine (P < 0.05) together with lower concentrations of myeloperoxidase, tumour necrosis factor-alpha, interleukin 1-ss, interferon-gamma, superoxide anion and superoxidase dismutase, malondialdehyde and inducible nitric oxide synthase (P < 0.05). CONCLUSION: In an experimental model of aortic reconstructive surgery, and compared with sevoflurane, propofol anesthesia is associated with less neutrophil infiltration, lower plasma proinflammatory cytokine levels, lower production of oxygen free radicals, less lipid peroxidation, and reduced inducible nitric oxide synthase activity. These observations suggest a possible renal protective effect of propofol in this surgical setting.     

New surface modification for Ti-6Al-7Nb alloy: oxygen diffusion hardening (ODH)

PVD-TiN coating and N+ implantation of Ti-6Al-7Nb alloy resulted in surface hardening to a depth of less 3 microns. The new oxygen diffusion hardening (ODH) treatment increased the hardness gradually to 50 microns. PUD-TiN showed an improvement in the tribological properties, while N+ implantation increased the PE wear rate. The wear rate of the ultrahigh-molecular-weight as well as the friction coefficient were reduced to one-half of the values achieved with the combination of CoCrMo-alloy when paired against the ODH-treated surface. In pairing with ZrO2-containing bone cement the ODH-treated surface showed only a minimal reaction.     

Na,K-Atpase in renal tissue of rats in the dynamics of experimental nephritis]

The authors undertook comparative study of the Na, K-ATPase activity in the red cells, ghost corpuscles, and in the cortex and medulla of kidneys of rats with experimental glomerulonephritis (GN) induced by injection of nephrotoxic serum (NTS), during an acute course of the process (1 and 2 weeks after NTS injection) and in chronic affection of the kidneys (10 weeks after NTS injection). The activity of the enzyme both in the red cells and in the ghost corpuscles was reduced significantly, by 28 and 22%, respectively, in the acute period of the disease (one week after NTS injection) but was restored to normal values in the period of chronic affection of the kidneys. The activity of the enzyme did not change in the cortex during the whole period of the study, but in the medulla it diminished in the acute period of the disease and remained reduced (by 27% on the average) during the chronic phase. It is concluded that reduction of the enzyme activity in the studied objects was not caused by the presence of endogenous inhibitors of the enzyme. It is suggested that reduction of Na, K-ATPase activity in the renal medulla may be one of the factors of increase of Na and water excretion in the urine in the chronic phase of GN.     

Antibodies against 5-hydroxymethyl-2'-deoxyuridine are associated with lifestyle factors and GSTM1 genotype: a report from the Malm? Diet and Cancer cohort.

Plasma autoantibodies (aAbs) against the oxidized DNA base derivative 5-hydroxymethyl-2'-deoxyuridine (5-HMdU) are potential biomarkers of cancer risk and oxidative stress. We examined their association with a number of cancer risk factors: smoking, alcohol habits, body fatness, and absence of the glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) in a sample from the population-based Malm? Diet and Cancer cohort (Sweden). This was a cross-sectional study of 264 men and 280 women, 46-67 years of age. Anti-5-HMdU aAb concentration was determined by an ELISA. Data on tobacco exposure were collected through a questionnaire. Alcohol consumption was estimated by a modified diet history method. Body fatness was assessed by a bioimpedance method. The absence or presence of genes coding for GSTM1 and GSTT1 was determined in granulocyte DNA by a multiplex PCR technique. aAb titers were significantly greater in those with high alcohol consumption. Current smokers lacking GSTM1, particularly men, had greater aAb titers compared with nonsmokers or persons expressing GSTM1. Body fatness was inversely associated with antibody titers in men. GSTT1 genotype was not associated with aAb titers. Overall, women had higher aAb titers than men. Adjustment for potential confounders (history of chronic diseases, anti-inflammatory medication, and season of blood sampling) did not change the results. Our study shows that a high alcohol consumption, smoking in combination with lack of GSTM1, and low body fatness (in men) is associated with high titers of anti-5-HMdU aAbs in this population.     

Assay of cytomegalovirus susceptibility to ganciclovir in renal and heart transplant recipients

Ganciclovir (GCV) prophylaxis or pre-emptive therapy significantly reduce the rate of cytomegalovirus (CMV) disease and viremia, but increase the potential for emergence of ganciclovir-resistant CMV strains. The inhibitor concentration at 50% (IC(50)) of GCV from 156 CMV isolates from 59 renal or heart transplant recipients was calculated by means of a rapid phenotypic susceptibility assay. Twenty-seven strains were from 14 patients undergoing GCV therapy. The IC(50) was higher in patients under the prophylaxis regimen. One CMV strain, from a heart transplant recipient, became GCV-resistant after 1 month of therapy (IC(50)=13.7 micromol/l). These data, together with clinical and virological markers, suggested that a switch to foscarnet was necessary, and good evolution was observed. Thus, assay of CMV susceptibility to GCV could be helpful in clinical management.     

The natural course of DSM-IV somatoform disorders and syndromes among adolescents and young adults: a prospective-longitudinal community study.

OBJECTIVE: Although somatoform disorders are assumed to be chronic clinical conditions, epidemiological knowledge on their natural course based on representative samples is not available. METHOD: Data come from a prospective epidemiologic study of adolescents and young adults in Munich, Germany. Respondents' diagnoses (N = 2548) at baseline and follow-up on average 42 months later are considered. The follow-up incidence, stability as well as selected baseline risk factors (sociodemographics, psychopathology, trauma exposure) for the incidence and stability of somatoform disorders and syndromes are prospectively examined. Diagnostic information was assessed by using the standardized Munich-Composite International Diagnostic Interview (M-CIDI). RESULTS: Over the follow-up period, incidence rate for any of the covered somatoform diagnoses was 25.7%. Stability for the overall group of any somatoform disorder/syndrome was 48%. Female gender, lower social class, the experience of any substance use, anxiety and affective disorder as well as the experience of traumatic sexual and physical threat events predicted new onsets of somatoform conditions, while stability was predicted by being female, prior existing substance use, affective and eating disorders as well as the experience of a serious accident. CONCLUSIONS: At least for a substantial proportion of individuals, the overall picture of somatization seems to be relatively stable, but with fluctuation in the symptom picture over time. Being female, the experience of substance use as well as anxiety disorder seem to constitute risk factors for the onset of new somatoform conditions as well as for a stable course over time.     

Vertical profile of Cs in soil

In this paper, a vertical distribution of ¹³⁷Cs in undisturbed soil was investigated experimentally and theoretically. Soil samples were taken from the surroundings of the city of Kragujevac in central Serbia during spring-summer of 2001. The sampling locations were chosen in such a way that the influence of soil characteristics on depth distribution of ¹³⁷Cs in soil could be investigated. Activity of ¹³⁷Cs in soil samples was measured using a HpGe detector and multi-channel analyzer. Based on vertical distribution of ¹³⁷Cs in soil which was measured for each of 10 locations, the diffusion coefficient of ¹³⁷Cs in soil was determined. In the next half-century, ¹³⁷Cs will remain as the source of the exposure. Fifteen years after the Chernobyl accident, and more than 30 years after nuclear probes, the largest activity of ¹³⁷Cs is still within 10 cm of the upper layer of the soil. This result confirms that the penetration of ¹³⁷Cs in soil is a very slow process. Experimental results were compared with two different Green functions and no major differences were found between them. While both functions fit experimental data well in the upper layer of soil, the fitting is not so good in deeper layers. Although the curves obtained by these two functions are very close to each other, there are some differences in the values of parameters acquired by them.