Caveolin-1 as a potential high-risk prostate cancer biomarker

Current diagnostic techniques of prostate cancer cannot efficiently distinguish the latent and low-risk forms from the high-risk significant forms of prostate cancer. Caveolin-1 (Cav-1), except other functions, plays an important role in cell transformation and the process of tumorigenesis. Furthermore, Cav-1 is involved in metastatic processes. It has also been shown that Cav-1 expression is induced under stress conditions, such as oxidative stress. The present study focused on the determination of prognostic markers of aggressive (high-grade) forms of prostate cancer. We determined serum Cav-1 and serum markers of antioxidant activity-glutathione (GSH), 2,2-diphenyl-1-picrylhydrazyl (DPPH), Trolox equivalent antioxidant capacity (TEAC), ferric-reducing antioxidant power (FRAP), N,N-dimethyl-1,4-diaminobenzene (DMPD), free radicals method (FRK) and blue chromium peroxide (Cro) in 97 serum samples (82 prostate cancer patients and 15 controls). We found insignificant differences in Cav-1 between the sera of patients and controls (5.69?in the cancer group vs. 5.42?ng/ml in the control group). However, we found a significant (p<0.004) 2.8-fold elevation of Cav-1 in high tumour stages (TNM T4) compared to lower stages and a significant positive association with histological grading (r=0.29, p=0.028). We also found that in patients with high serum Cav-1 the antioxidant capacity of the body is reduced. These findings indicate that Cav-1 may be an interesting tool for the prediction of disease burden.     

Effect of zinc(II) ions on the expression of pro- and anti-apoptotic factors in high-grade prostate carcinoma cells

Several typical characteristics of prostate tissue have been identified including the ability to accumulate zinc(II). However, this feature of prostate cells is lost during carcinogenesis and, thus, prostate cells are unable to accumulate zinc(II) ions in high levels. Therefore, we can expect that zinc(II) ions can significantly contribute to the progression of tumour disease and to the ability of prostate cell lines to metastasize. In this study, we aimed our attention on determining the expression of Bcl-2, c-Fos, c-Jun, Ki-67, NF-κB and p53 genes in two prostate cell lines, as the 22Rv1 cell line, a model of aggressive partially androgen-sensitive prostate cancer and the PNT1A cell line, a normal prostate cell line model. Moreover, we were interested in the mechanisms through which exposure of these cell lines to zinc(II) ions could influence expression of the above-mentioned genes. We found that zinc(II) ions caused elevated expression of Ki-67, a marker of proliferation, extremely low expression of p53, high expression of Bcl-2 and no changes in the expression of p53. Our experimental data show different effect of zinc(II) ions on expression of the above-mentioned regulatory genes, which may give us more information on their impact on cancer development and progression with possible using for cancer therapy.     

Hydroxyurea in sickle cell disease--a study of clinico-pharmacological efficacy in the Indian haplotype

There is clinical variability in the presentation of sickle cell disease among Indians. Vaso-occlusive crisis is common among non-tribal patients. Hydroxyurea, induces fetal hemoglobin (HbF) synthesis and reduces the clinical severity of sickle cell disease but individual patients have a variable response. This study was undertaken to investigate the efficacy and safety of hydroxyurea in Indians with severe manifestations where the beta(s) gene is linked to the Arab-Indian haplotype and is associated with higher HbF levels. Seventy-seven patients (29 adult sickle homozygous, 25 pediatric sickle homozygous, 23 adult sickle beta-thalassemia) selected for hydroxyurea therapy were evaluated for clinical, hematological, biochemical and genetic parameters and were followed for 24 months. Ninety-eight point seven percent of the sickle chromosomes were linked to the Arab-Indian haplotype, 27% of patients had associated alpha thalassemia and 65% were Xmn I +/+. Seventy-eight percent of the patients had no further crises after starting hydroxyurea. This effect was accompanied by a significant increase in HbF (p<0.001), but this increase was variable in individual cases. There was also an increase in gamma gene mRNA expression in the few cases so studied. Hemoglobin levels increased significantly (p<0.001) resulting in the cessation of blood transfusions. Leucopoenia was observed in one patient. Hydroxyurea was effective in reducing the clinical severity in Indian patients who initially had higher HbF levels and the presence of ameliorating factors, such as alpha-thalassemia and the Xmn I polymorphism. Hydroxyurea therapy with careful monitoring can thus change the quality of life of Indians with sickle cell disease.     

DTI derived indices correlate with immunohistochemistry obtained matrix metalloproteinase (MMP-9) expression in cellular fraction of brain tuberculoma

We performed in vivo diffusion tensor imaging (DTI) in a total of 33 patients with brain tuberculomas (BT). Thirteen of them had surgical excision of the lesion as it was clinically indicated, and in these samples matrix metalloproteinase-9 (MMP-9) expression was quantified. We correlated the results of DTI indices like fractional anisotropy (FA), mean diffusivity (MD), linear anisotropy (CL), planar anisotropy (CP) and spherical anisotropy (CS) with MMP-9 expression. In addition, the remaining 20 patients had serial DTI studies while on specific anti-tuberculous drug therapy and DTI indices in these patients were quantified. The FA, CL and CP significantly decreased while MD and CS significantly increased in BT compared to normal white matter. The FA, CL and CP showed negative correlation with MMP-9 while CS correlated positively. In serial follow-up studies in 20 patients FA, CL and CP showed significant increase while CS decreased significantly over time. We conclude that DTI indices show strong correlation with MMP-9 and these may be used as a surrogate marker of MMP-9 expression in BT. In addition, these indices may be of value in assessing the therapeutic response in patients with BT who are treated only with specific anti-tuberculous drugs.     

Comparative Evaluation of the Cerebral and Cerebellar White Matter Development in Pediatric Age Group using Quantitative Diffusion Tensor Imaging

Age-dependent changes in the normal cerebral white matter have been reported; however, there is no study on normal cerebellar white matter maturation in developing brain using diffusion tensor imaging (DTI). We performed DTI in 21 children who had normal neurological assessment along with no evidence of any abnormality on imaging. The aim of this study was to compare the age-related changes in fractional anisotropy (FA) and mean diffusivity (MD) quantified from cerebral white matter (splenium and genu of the corpus callosum and posterior limb of the internal capsule) and cerebellar white matter (middle cerebellar peduncles, superior cerebellar peduncles, and inferior cerebellar peduncles) regions in healthy children ranging in age from birth to 132 months. Log-linear regression model showed best fit to describe the age-related changes in FA and MD both for cerebral and cerebellar white matter. In cerebral white matter, an initial sharp increase in FA was observed up to the age of 24 months followed by a gradual increase up to 132 months. In cerebellar white matter, sharp increase in FA was observed up to 36 months, which then followed a gradual increase. However, MD showed a sharp decrease in cerebral white matter up to 24 months followed by a more gradual decrease thereafter, while in cerebellar white matter after an initial decrease (6 months), it followed a stable pattern. This study provides normative database of brain white matter development from neonates to childhood. This quantitative information may be useful for assessing brain maturation in patients with developmental delay of the cerebral and cerebellar white matter.     

Comparison of forehead and digit oximetry in surgical/trauma patients at risk for decreased peripheral perfusion

OBJECTIVE: Measurement of pulse oximetry (Spo(2)) is often impaired in critically ill patients. Forehead reflectance oximetry, the Max-Fast (Nellcor, Pleasanton, CA), may be less susceptible to poor tissue perfusion and could improve accuracy of oxygen saturation measurement. The objective of this study was to evaluate the use of forehead oximetry measures in critically ill surgical/trauma patients. METHODS: A prospective interventional study of 30 critically ill surgical/trauma patients at risk for decreased peripheral perfusion, as evidenced by need for vasopressor support (24 patients), transfusion of more than 6 unit packed cells in 24 hours (two patients), or an inability to obtain consistent saturation from a digit sensor (four patients), compared forehead and digit-based oximeter Spo(2) readings with co-oximetry (Sao(2)) measurements from arterial blood samples. Sao(2) values were converted to functional oxygen saturation (SO(2)) measurements for the final comparison. Patients were fitted with forehead (Nellcor Max-Fast) and digit (Nellcor Max A; digit 1) sensors connected to Nellcor OxiMax N-595 oximeters and a digit sensor (Nellcor Max A; digit 2) connected to a multiparameter monitor (Philips CMS [Andover, MA]). Three measurements of Sao(2) were obtained from each subject over a 24-hour time period, and simultaneous measurements of Spo(2) were recorded from the three monitors. RESULTS: The three Spo(2) measurements (forehead, digit 1, and digit 2) were compared with SO(2) values using the Bland-Altman method to assess agreement. Forehead measurements demonstrated a mean bias of -1.39, whereas digit 1 was -2.61 and digit 2 was -3.84. Pearson correlations (r) for forehead, digit 1, and digit 2 with SO(2) were .834, .433, and .254, respectively. There were fewer unsuccessful measurements with the forehead oximetry technique. CONCLUSIONS: Forehead sensors improve measurement of oxygen saturation in critically ill surgical/trauma patients at risk for decreased peripheral perfusion.     

REM behavior disorder (RBD) can be one of the first symptoms of childhood narcolepsy

More than one in three adult patients suffering from narcolepsy-cataplexy experience rapid eye movement (REM) behavior disorder (RBD), while RBD in childhood is extremely rare. We present the cases of two girls (aged 9 and 7 years old) with narcolepsy-cataplexy, in whom RBD was one of the first symptoms of the disease. The coincidence of RBD was seen by nocturnal video-polysomnography (v-PSG), and narcolepsy was diagnosed from short sleep latency and multiple sleep onset REMs (SOREMs) during a multiple sleep latency test (MSLT). Both girls were human leukocyte antigen (HLA)-DQB1 *0602 positive, and their cerebrospinal fluid (CSF) hypocretin level (Hcrt-1) was extremely low.     

Esophageal Doppler monitoring for hemodynamic assessment

This article reviews the importance of hemodynamic monitoring in adding to the clinical assessment of critically ill patients. The esophageal Doppler monitor (EDM) provides a less invasive way of obtaining hemodynamic information quickly and safely at the bedside. The concepts of Doppler signal acquisition and important nursing considerations are reviewed. Case studies are provided to understand how data from the EDM can impact patient care decisions at the bedside.