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International Journal Of Biomedical Science[JOURNAL]

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An in vitro model of cartilage degradation by chondrocytes in a three-dimensional culture system.

Nakashima K, Nakatsuka K, Yamashita K … +2 more , Kenichi K, Taro H

Int J Biomed Sci · 2012 Dec · PMID 23675280

OBJECTIVE: Using the alginate bead three-dimensional culturing method, which is considered to be advantageous for the in vitro study of chondrocytes, we confirmed earlier reports concerning the inhibitory effect of TGF-β... OBJECTIVE: Using the alginate bead three-dimensional culturing method, which is considered to be advantageous for the in vitro study of chondrocytes, we confirmed earlier reports concerning the inhibitory effect of TGF-β on IL-1β-induced cartilage destruction and serially evaluated changes in proteinases and their inhibitors in cartilage destruction. METHODS: Chondrocytes were cultured on alginate beads with IL-1β or TGF-β alone or both. The glycosaminoglycan (GAG) concentration in the culture medium was determined by use of the DMMB assay; and the levels of TIMP-1, -2 and proMMP-3 were measured with their respective sandwich EIAs. Sections of the beads were prepared and stained with toluidine blue or anti-TIMP-1 -2, -3 antibodies. The numbers of chondrocytes negative for pericellular proteoglycan staining and TIMP-positive chondrocytes were counted, and positive staining for TIMP-3 in the extracellular matrix was examined. RT-PCR was performed to evaluate the gene expression of TIMP-1, -2, -3, and MMP-3. RESULTS: The number of TIMP-1(+)chondrocytes, TIMP-1 concentration in the culture medium, and TIMP-1-gene expression all increased maximally as early as 6 hours after IL-1β stimulation, and then gradually decreased. However, the number of cells immunopositive for TIMP-3 increased somewhat later. GAG and proMMP-3 concentrations in the culture medium increased gradually with time. The number of TIMP-3(+)chondrocytes and positive staining for TIMP-3 in the extracellular matrix significantly increased in the TGF-β group compared with the values for the IL-1β group. The proMMP-3 concentration in the culture medium of TGF-β-treated cells was significantly decreased compared with that for the IL-1β-treated ones at all times examined. DISCUSSION: We suggest that TIMP-1 plays a primary role in the prevention of articular cartilage destruction in its early stage but that TIMP-3 gradually takes over this role. Also, TGF-β was shown to regulate these TIMPs and act as a suppressor of articular cartilage destruction. These results suggest that TIMP-1 and TIMP-3 are closely involved in preventing the progression of joint disorders such as OA.

Acute myeloid leukaemia of donor cell origin developing 17 years after allogenic hematopoietic cell transplantation for acute promyelocytic leukaemia.

Jiménez P, Alvarez JC, Garrido P … +3 more , Lorente JA, Palacios J, Ruiz-Cabello F

Int J Biomed Sci · 2012 Dec · PMID 23675279

Donor cell leukaemia (DCL) is a rare complication of allogenic hematopoietic cell transplantation (HCT). We report the case of a female patient with acute promyelocytic leukaemia (APL), FAB type M3, who developed acute m... Donor cell leukaemia (DCL) is a rare complication of allogenic hematopoietic cell transplantation (HCT). We report the case of a female patient with acute promyelocytic leukaemia (APL), FAB type M3, who developed acute myeloid leukaemia (AML) type M5 of donor origin 17 years after allogenic bone marrow transplantation (BMT) from her HLA-matched sister. Morphology and immunophenotyping showed differences with the initial leukaemia, and short tandem repeat (STR) analysis confirmed donor-type haematopoiesis. Interphase fluorescence in situ hybridisation (FISH) showed an 11q23 deletion. Given that the latency period between transplant and development of leukaemia was the longest reported to date, we discuss the mechanisms underlying delayed leukaemia onset.

New view on the initial development site and radiographic classification system of osteoarthritis of the knee based on radiographic analysis.

Moon KH

Int J Biomed Sci · 2012 Dec · PMID 23675278

INTRODUCTION: Radiographic pathology of severe osteoarthritis of the knee (OAK) such as severe osteophyte at tibial spine (TS), compartment narrowing, marginal osteophyte, and subchondral sclerosis is well known. Kellgre... INTRODUCTION: Radiographic pathology of severe osteoarthritis of the knee (OAK) such as severe osteophyte at tibial spine (TS), compartment narrowing, marginal osteophyte, and subchondral sclerosis is well known. Kellgren-Lawrence grading system, which is widely used to diagnose OAK, describes narrowing-marginal osteophyte in 4-grades but uses osteophyte at TS only as evidence of OAK without detailed-grading. However, kinematically the knee employs medial TS as an axis while medial and lateral compartments carry the load, suggesting that early OAK would occur sooner at TS than at compartment. Then, Kellgren-Lawrence system may be inadequate to diagnose early-stage OAK manifested as a subtle osteophyte at TS without narrowing-marginal osteophyte. This undiagnosed-OAK will deteriorate becoming a contributing factor in an increasing incidence of OAK. METHODS: This study developed a radiographic OAK-marker based on both osteophyte at TS and compartment narrowing-marginal osteophyte and graded as normal, mild, moderate, and severe. With this marker, both knee radiographs of 1,728 patients with knee pain were analyzed. RESULTS: Among 611 early-stage mild OAK, 562 or 92% started at TS and 49 or 8% at compartment. It suggests the initial development site of OAK, helping develop new site-specific radiographic classification system of OAK accurately to diagnose all severity of OAK at early, intermediate, or late-stage. It showed that Kellgren-Lawrence system missed 92.0% of early-stage mild OAK from diagnosis. CONCLUSIONS: A subtle osteophyte at TS is the earliest radiographic sign of OAK. A new radiographic classification system of OAK was suggested for accurate diagnosis of all OAK in severity and at stage.

Multiple Sites of Type II Site Ligand (Luteolin and BMHPC) Regulation of Gene Expression in PC-3 Cells.

Markaverich BM, Vijjeswarapu M

Int J Biomed Sci · 2012 Dec · PMID 23675277

Type II [(3)H]estradiol binding site ligands including luteolin (a naturally occurring bioflavonoid) and synthetic compounds such as 2,6-bis((3-methoxy-4-hydroxyphenyl)methylene)cyclohexanone (BMHPC) inhibit normal and m... Type II [(3)H]estradiol binding site ligands including luteolin (a naturally occurring bioflavonoid) and synthetic compounds such as 2,6-bis((3-methoxy-4-hydroxyphenyl)methylene)cyclohexanone (BMHPC) inhibit normal and malignant prostate cell (PC-3, LNCaP, DU-145) proliferation in vitro and in vivo. Type II sites represent a binding domain on histone H4 possibly involved in an epigenetic mechanism for controlling gene transcription. Treatment of PC-3 human prostate cancer cells with luteolin or BMHPC modulated the expression of a number of genes in the epidermal growth factor receptor signaling pathway (EGFRSP) and cell cycle pathway (CCP). Pronounced stimulation (400-2000% of control) of c-FOS and p21 RNA expression was observed, suggesting that these were primary sites of action. Both compounds also caused irreversible G2/M arrest (p<0.001). siRNA's for c-FOS or p21 reduced the RNA expression of their respective targets by 85-95%, with minimal effects on cell proliferation. Furthermore, neither siRNA alone (single knockdown), or in combination (double knockdown), blocked luteolin or BMHPC inhibition of PC-3 cell proliferation. Thus, although c-FOS and p21 are known to modulate the expression of genes in the ESGRSP (EGFR, SOS, GRB2, JNK1, MKK4, RasGAP) and CCP (CCNA2, CCNE2, CDC25A, CDKN1A, CDKN1B, p27, PLK1) involved in the regulation of cell proliferation by luteolin and BMHPC, the c-FOS and p21 siRNA knockdown studies reported here suggest that c-FOS and p21 may be secondary bystanders in the overall response to these ligands in the regulation of PC-3 cell proliferation.

Liquid chromatographic determination of alogliptin in bulk and in its pharmaceutical preparation.

El-Bagary RI, Elkady EF, Ayoub BM

Int J Biomed Sci · 2012 Sep · PMID 23675276

In this work, a reversed-phase liquid chromatographic (RP-LC) method has been developed for the determination of alogliptin (ALG) based on isocratic elution using a mobile phase consisting of potassium dihydrogen phospha... In this work, a reversed-phase liquid chromatographic (RP-LC) method has been developed for the determination of alogliptin (ALG) based on isocratic elution using a mobile phase consisting of potassium dihydrogen phosphate buffer pH (4.6)-acetonitrile (20:80, v/v) at a flow rate of 1 mL min(-1) with UV detection at 215 nm. Chromatographic separation was achieved on a Symmetry(®) cyanide column (150 mm × 4.6 mm, 5 μm). Linearity, accuracy and precision were found to be acceptable over the concentration range of 5-160 μg mL(-1) for ALG in bulk. The optimized method was validated and proved to be specific, robust and accurate for the quality control of ALG in pharmaceutical preparations.

Liquid chromatographic determination of linagliptin in bulk, in plasma and in its pharmaceutical preparation.

El-Bagary RI, Elkady EF, Ayoub BM

Int J Biomed Sci · 2012 Sep · PMID 23675275

In this work, two reversed-phase liquid chromatographic (RP-LC) methods have been developed for the determination of linagliptin (LNG) based on isocratic elution using a mobile phase consisting of potassium dihydrogen ph... In this work, two reversed-phase liquid chromatographic (RP-LC) methods have been developed for the determination of linagliptin (LNG) based on isocratic elution using a mobile phase consisting of potassium dihydrogen phosphate buffer pH (4.6)-acetonitrile(20:80, v/v) at a flow rate of 1 mL min(-1). Two detection techniques have been applied either UV detection at 299 nm in the first method or fluorometric detection at 239 nm for excitation and 355 nm for emission in the second method. Chromatographic separation in the two methods was achieved on a Symmetry(®) cyanide column (150 mm × 4.6 mm, 5 μm). Linearity, accuracy and precision were found to be acceptable over the concentration ranges of 2.5-80 μg mL(-1) for LNG in bulk and 2.5-15 μg mL(-1) for LNG in plasma with the first method and 5-160 μg mL(-1) for LNG in bulk with the second method. The optimized methods were validated and proved to be specific, robust and accurate for the quality control of the cited drug in its pharmaceutical preparation.

Spectrophotometric methods based on charge transfer complexation reactions for the determination of saxagliptin in bulk and pharmaceutical preparation.

El-Bagary RI, Elkady EF, Ayoub BM

Int J Biomed Sci · 2012 Sep · PMID 23675274

Simple, accurate and precise spectrophotometric methods have been developed for the determination of saxagliptin in bulk and dosage forms. The proposed methods are based on the charge transfer complexes of saxagliptin wi... Simple, accurate and precise spectrophotometric methods have been developed for the determination of saxagliptin in bulk and dosage forms. The proposed methods are based on the charge transfer complexes of saxagliptin with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and 7,7,8,8-tetracyanoquinodimethane (TCNQ). All the variables were studied to optimize the reactions' conditions. Beer's law was obeyed in the concentration ranges of 50-300 μg/ml and 10-110 μg/ml with DDQ and TCNQ, respectively. The developed methods were validated and proved to be precise and accurate for the quality control of the saxagliptinin its pharmaceutical dosage form.

Developmental Changes of Catecholamine-mediating Enzyme - Dopamine-β- Hydroxylase and Its Cofactors in Central and Peripheral Tissues and Serum of Long-Evans Rats.

Rahman MK, Choudhary MI, Islam MR … +1 more , Hafizur RM

Int J Biomed Sci · 2012 Sep · PMID 23675273

Dopoamine-β-hydroxylase (DBH) is a catecholamine-synthesizing enzyme which catalyzes the formation of norepinephrine from dopamine. Fifty nine Long-Evans rats of 1 week-old were used to grow on normal diets in 7 differen... Dopoamine-β-hydroxylase (DBH) is a catecholamine-synthesizing enzyme which catalyzes the formation of norepinephrine from dopamine. Fifty nine Long-Evans rats of 1 week-old were used to grow on normal diets in 7 different developmental stages, viz., 15 rats in 1 week-old group, 9 rats in 2 weeks-old group, and the remaining 35 rats were divided equally into five groups, 7 rats in each group of 5-, 8-, 12-, 15- and 27-weeks old for systematic developmental studies of DBH. At the end of each developmental period, weights of rats were recorded for that specific group and they were sacrificed. The brain tissues (caudate nucleus, hypothalamus, brain stem, colliculi, cerebral cortex and cerebellum) and peripheral tissues (liver, heart, kidney, adrenal, spleen, pancreas, lung and small intestine) and serum were collected. The brain tissues had the highest activity (expressed as nmole/min/g of wet weight tissue) of DBH at 5 weeks of age. The hypothalamus had the highest activities (11.5 ± 2.2) and the lowest activities were found in the cerebellum (5.7 ± 0.9). The peripheral tissues also showed the peak DBH activities at 5 weeks of age and adrenals had the highest activities (59.2 ± 7.0) among the central and peripheral tissues. The serum DBH activities were relatively low (1.3 ± 0.2) as compared to those in all other tissues. The highest serum DBH activities (1.28 ± 21 nmole/min/ml of serum) were also found in the 5- weeks-old rats. The specific activities of DBH were also measured in various developmental stages and the results were found to be in agreement with the DBH activities expressed in terms of gram of tissues or milliliter of serum. The Km and Vmax values for DBH were measured in the serum samples of each group and the highest Vmax values (78.3 ± 21.2 pmol/min/mg protein) were obtained at 5 weeks of age; while the lowest Km values (0.52 ± 0.04 mM) were obtained at this stage of age.

Effects of aspirin on rheological properties of erythrocytes in vitro.

Elblbesy MA, Hereba AR, Shawki MM

Int J Biomed Sci · 2012 Sep · PMID 23675272

Aspirin is of proven value as an antithrombotic drug. In unstable angina it reduces the risk of death and myocardial infarction by half. Most studies on the mechanism of action of aspirin have concentrated on the effect... Aspirin is of proven value as an antithrombotic drug. In unstable angina it reduces the risk of death and myocardial infarction by half. Most studies on the mechanism of action of aspirin have concentrated on the effect of aspirin on platelets. In the present study we have tried to prove that there is another biophysical mechanism of aspirin, and that is through the effect of aspirin on erythrocytes. In this study ten blood samples were incubated with aspirin at different concentrations. The fractal dimension of erythrocytes subjected to shear rates from 5 s(-1) to 30 s(-1), in a cone and plate device designed and constructed in our lab, was calculated by processing the images of the erythrocyte. At each shear rate, the fractal dimensions of the erythrocytes were found to be strongly correlated with aspirin concentration. It is suggested that further studies using different biophysical methods must be carried out to detect the other mechanisms underlying the effect of aspirin on different blood cells.

Health related quality of life of stroke survivors: experience of a stroke unit.

Abubakar SA, Isezuo SA

Int J Biomed Sci · 2012 Sep · PMID 23675271

BACKGROUND: Stroke has a major impact on survivors including Health related Quality of life (HRQoL). HRQoL measurements are potentially more relevant to patients than measurements of impairments or disability and are an... BACKGROUND: Stroke has a major impact on survivors including Health related Quality of life (HRQoL). HRQoL measurements are potentially more relevant to patients than measurements of impairments or disability and are an important index of outcome after stroke that can facilitate a broader description of disease and outcome. This study examined the factors associated with HRQoL of stroke survivors. METHODS: In a cross-sectional and descriptive correlational design, 62 patients were prospectively enrolled and interviewed 3 months post stroke in neurology out-patient clinic. After case identification, functional status (handicap) was determined using the Modified Rankin Scale (MRS), while Zung Depression Self-Rating Scale (ZDS) was used to determine presence of depression. HRQoL was assessed using the Stroke Impact Scale-16 (SIS-16). Age, sex, duration of formal education, depression and degree of disability were correlated with HRQoL in multiple logistic regressions. RESULTS: The mean age of patients was 54.4 ± 9.9 years. Mean duration of formal education was significantly higher in males than females (p value=0.007). About one third (29%) of the stroke survivors were depressed and more than half (54.8%) had good recovery. Function status measured by modified Rankin Scale and depression were independent determinants of poor HRQoL. CONCLUSION: Functional status and depression were identified as independent factors affecting HRQoL of stroke survivors.

The Control of Stress Induced Type I Diabetes Mellitus in Humans through the Hepatic Synthesis of Insulin by the Stimulation of Nitric Oxide Production.

Ghosh R, Bhattacharya R, Bhattacharya G … +1 more , Sinha AK

Int J Biomed Sci · 2012 Sep · PMID 23675270

The role of stress induced development of Type-1 diabetes mellitus (T1DM) as opposed to autoimmunity remains obscure. It has been reported that a stress induced protein, identified to be dermcidin isoform 2 (dermcidin) i... The role of stress induced development of Type-1 diabetes mellitus (T1DM) as opposed to autoimmunity remains obscure. It has been reported that a stress induced protein, identified to be dermcidin isoform 2 (dermcidin) inhibited insulin synthesis in both the pancreatic β cells and the hepatic cells. As dermcidin effect could be neutralized by the increased production of systemic nitric oxide (NO), investigations were carried out to determine the feasibility of controlling stress induced T1DM through the neutralization of dermcidin by systemic increase of NO. To determine the role of plasma dermcidin level in T1DM subjects (n=45), if any, when the plasma dermcidin level were determined, it was found that the protein level was increased in 65% of the participating volunteers. Efforts were made to normalize the plasma glucose level (median=175 mg/dL) in these T1DM subjects by systemic increase of NO by applying a cotton pad containing 0.28mmol sodium nitroprusside on the abdominal skin. It was found that the systemic increase of NO level decreased the blood glucose level of 275 mg/dL (median) to 115 mg/dL (median) in these volunteers within 24 h with concomitant increase of plasma insulin level from 7.5 μunits/dL to 101 μunits/dL at the same time. The increase of plasma insulin level was accompanied by the decrease of dermcidin level of 124.5 nM to 18 nM with increase of NO from 0.43 ± 0.19 nM to 4.1 ± 1.56 nM. The results suggested that the stress induced T1DM by dermcidin could be controlled by the systemic increase of NO which in consequence led to increased synthesis of insulin.

Salivary ceruloplasmin ferroxidase & oxidase activities in celiac patients.

Hasan HR, Ghadhban JM, Abudal Kadhum ZI

Int J Biomed Sci · 2012 Sep · PMID 23675269

The aim of the current study was to evaluate salivary ferroxidase ceruloplasmin activities in celiac patients with different histopathological severity. This study included 75 celiac patients with different mean age (18.... The aim of the current study was to evaluate salivary ferroxidase ceruloplasmin activities in celiac patients with different histopathological severity. This study included 75 celiac patients with different mean age (18.68 ± 11.13) year, who had positive screen for celiac antibodies, and who had gastrointestinal symptoms. In order to simplify the comparison with the healthy control group, celiac patients were divided into two groups according to their histopathological severity: severe (marsh IIIa, b, c) & less severe (marsh 0, I). All these patients have been evaluating for salivary ceruloplasmin (Cp) concentration and Cp ferroxidase activities. To confirm the presence of the enzymatic activity of this protein, polyacrylamide gel electrophoresis was carried out and then stained for Cp ferroxidase, as well as for Cp oxidase activity. Furthermore, the concentrations of salivary total protein, albumin, and globulin were measured in the studied groups. A significant increase (p<0.05) in salivary concentration of ceruloplasmin was found in all above mentioned patients groups in comparison to that of the control group, except for total villous atrophy (marsh IIIc) patients subgroup. Salivary Cp ferroxidase activity revealed statistically significant decrease among the patient groups as well as between them and the control group. The result of salivary total protein and globulin showed presence a significant increase (p<0.05) in comparison to that of the control group. Meanwhile albumin levels was found to increase non-significantly (p=0.186).

Histological and Demographic Characteristics of the Distribution of Brain and Central Nervous System Tumors' Sizes: Results from SEER Registries Using Statistical Methods.

Pokhrel KP, Vovoras D, Tsokos CP

Int J Biomed Sci · 2012 Sep · PMID 23675268

The examination of brain tumor growth and its variability among cancer patients is an important aspect of epidemiologic and medical data. Several studies for tumors of brain interpreted descriptive data, in this study we... The examination of brain tumor growth and its variability among cancer patients is an important aspect of epidemiologic and medical data. Several studies for tumors of brain interpreted descriptive data, in this study we perform inference in the extent possible, suggesting possible explanations for the differentiation in the survival rates apparent in the epidemiologic data. Population based information from nine registries in the USA are classified with respect to age, gender, race and tumor histology to study tumor size variation. The Weibull and Dagum distributions are fitted to the highly skewed tumor sizes distributions, the parametric analysis of the tumor sizes showed significant differentiation between sexes, increased skewness for both the male and female populations, as well as decreased kurtosis for the black female population. The effect of population characteristics on the distribution of tumor sizes is estimated by quantile regression model and then compared with the ordinary least squares results. The higher quantiles of the distribution of tumor sizes for whites are significantly higher than those of other races. Our model predicted that the effect of age in the lower quantiles of the tumor sizes distribution is negative given the variables race and sex. We apply probability and regression models to explore the effects of demographic and histology types and observe significant racial and gender differences in the form of the distributions. Efforts are made to link tumor size data with available survival rates in relation to other prognostic variables.

Simultaneous determination of metformin, nateglinide and gliclazide in pharmaceutical preparations using micellar liquid chromatography.

El-Wasseef DR

Int J Biomed Sci · 2012 Jun · PMID 23675267

A micellar chromatographic method has been developed and validated for simultaneous separation and determination of metformin(MF), nateglinide (NT) and gliclazide (GL). The separation was carried out using a Nucleosil C1... A micellar chromatographic method has been developed and validated for simultaneous separation and determination of metformin(MF), nateglinide (NT) and gliclazide (GL). The separation was carried out using a Nucleosil C18 column, 150 mm × 4.6 mm i.d., 5 μm particle size, using micellar mobile phase consisting of sodium dodecyl sulphate (SDS), n-propanol with UV detection. The optimum conditions for the simultaneous separation of the three drugs were 0.12 M SDS, 10% (v/v) n-popanol, 0.3% triethylamine adjusted to pH5.6 with a flow rate of 1 ml.min(-1) and detection at 254 nm. The limit of detection (LOD) of MF, NT, GL were 0.047, 0.00115, 0.036 μg.mL(-1) respectively. The method showed good linearity in the ranges of 0.4-16 μg.mL(-1), (r(2)=0.999), 0.8-16 μg.ml(-1) (r(2)=0.999) and 1-40 μg.ml(-1) (r(2)=0.999) for MF, NT, GL respectively. The suggested method was successfully applied for the analysis of the three antidiabetic drugs in pharmaceutical preparations with average recoveries of 99.66%, 100.08% and 100.31% for MT, NT and GL respectively. The results obtained were in good agreement with those obtained from comparison methods. The method was validated regarding accuracy and precision.

Reliability of the Mid Upper Arm Circumference for the Assessment of Wasting among Children Aged 12-59 Months in Urban Ibadan, Nigeria.

Dairo MD, Fatokun ME, Kuti M

Int J Biomed Sci · 2012 Jun · PMID 23675266

Although the mid upper arm circumference (MUAC) is used as a proxy to assess wasting in children, its validity abounds in controversies. This study therefore assessed the validity of MUAC as a measure of nutritional stat... Although the mid upper arm circumference (MUAC) is used as a proxy to assess wasting in children, its validity abounds in controversies. This study therefore assessed the validity of MUAC as a measure of nutritional status among children aged 12-59 months in urban setting in western Nigeria. A cross sectional study of children aged 12-59 months in selected nursery schools in Moniya, Akinyele local government area, Oyo state was carried out between February to April 2010. The age, weight, length and MUAC, were obtained from the school children who were selected through total sampling. The sensitivity, specificity, positive predictive value, and negative predictive values of the MUAC were determined using weight for age as gold standard (underweight). Z-Scores for anthropometric indicators were calculated using EPI-NUT programme. Receivers operating curve was prepared to determine the optimal cut off of MUAC for the sensitivity and specificity. The overall prevalence of under nutrition among the respondents was 5.6%. The mean mid upper arm circumference was 15.47 ± 1.4 cm and appears to increase with age from 11.49 ± 3.0 at 12-23 months and peaks at age five with a value of 18.05 ± 3.5. At 13.5 cm cut off, the sensitivity of MUAC is 20%, and the specificity is 95.3%, with a Kappa of 16.7%. The receivers operating curve reveals an optimum cut off of 15.5 cm with optimal but improved MUAC sensitivity of 80% and specificity of 53.5%. Thus MUAC was a poorly sensitive indicator of under nutrition at a cut-off below 13.5 cm but highly sensitive at 15.5 cm. A higher cut off value is therefore for recommended for screening for acute malnutrition among under five children.

The "Cross Talk" between the Receptors of Insulin, Estrogen and Progesterone in Neutrophils in the Synthesis of Maspin through Nitric Oxide in Breast Cancer.

Bhattacharjee KG, Bhattacharyya M, Halder UC … +2 more , Jana P, Sinha AK

Int J Biomed Sci · 2012 Jun · PMID 23675265

PURPOSE: The binding of either insulin, or estrogen or progesterone to their specific receptors on neutrophils has been reported to stimulate nitric oxide (NO) induced maspin synthesis in these cells. Experiments were ca... PURPOSE: The binding of either insulin, or estrogen or progesterone to their specific receptors on neutrophils has been reported to stimulate nitric oxide (NO) induced maspin synthesis in these cells. Experiments were carried out to determine the role of insulin receptor interaction in the nitric oxide induced maspin synthesis in neutrophils that was effected by estrogen or progesterone. METHODS: Estrogen receptor positive (ER+) and progesterone receptor positive (PR+) neutrophils were isolated from the blood cancer subjects. Maspin was determined by enzyme linked immunosorbent assay after in vitro translation of maspin mRNA. NO was determined by methemoglobin method. RESULTS: It was found that pre incubation of normal neutrophils with insulin to reach equilibrium binding decreased both ER and PR numbers by ≈50% without changing the dissociation constants of the steroids binding. The reduction of ER or PR numbers on neutrophils due to the pretreatment with insulin resulted in the decreased NO induced maspin synthesis from 2.383 ± 0.014 nM to 1.454 ± 0.004 nM in the case of estrogen and in the decrease of maspin synthesis from 2.329 ± 0.012 nM to 1.410 ± 0.002 nM in the case of progesterone. The incubation of ER+ neutrophils or PR+ neutrophils with insulin further decreased the maspin synthesis from 1.422 ± 0.029 nM to 0.790 ± 0.004 nM in the case of estrogen, and from 1.138 ± 0.024 nM to 0.555 ± 0.003 nM maspin in the case of progesterone respectively compared to normal control. CONCLUSION: These results suggested that a "cross-talk" between the insulin receptors and the steroid receptors down regulated maspin synthesis in normal and in breast cancer neutrophils.

A Single Nucleotide Polymorphism in the Phospholipase D1 Gene is Associated with Risk of Non-Small Cell Lung Cancer.

Ahn MJ, Park SY, Kim WK … +6 more , Cho JH, Chang BJ, Kim DJ, Ahn JS, Park K, Han JS

Int J Biomed Sci · 2012 Jun · PMID 23675264

Phospholipase D (PLD) has an important role in various biological functions including vesicular transport, endocytosis, exocytosis, cell migration, and mitosis. These cellular biological processes are deregulated in the... Phospholipase D (PLD) has an important role in various biological functions including vesicular transport, endocytosis, exocytosis, cell migration, and mitosis. These cellular biological processes are deregulated in the development of various human tumors. In order to explore the relationship between the PLD1 gene and risk of non-small cell lung cancer (NSCLC), single nucleotide polymorphisms (SNP) in the PLD1 exon region were surveyed in 211 NSCLC patients and 205 normal controls. In this study, we identified six SNPs at exon 23 in the PLD1 gene. Among the six SNPs, the most notable was a heterozygous A to C transition at nucleotide 2698 (A2698C, p<0.001). In addition, the genotype frequencies of A2744C (AC+CC) and A2756C (AC+CC) were associated with gender (female, A2744C and A2756C: p=0.071) in NSCLC patients. Interestingly, although the SNP A2698C did not cause change in amino acid, correlation between odd ratio of NSCLC patients and the SNP A2698C was observed to be statistically significant.

Electrical Field Stimulation with a Novel Platform: Effect on Cardiomyocyte Gene Expression but not on Orientation.

Kujala K, Ahola A, Pekkanen-Mattila M … +4 more , Ikonen L, Kerkelä E, Hyttinen J, Aalto-Setälä K

Int J Biomed Sci · 2012 Jun · PMID 23675263

Electrical field stimulation has been shown to improve cardiac cell alignment and functional properties. In this study, neonatal rat cardiomyocytes were exposed to both long-term and short-term stimulation with the goal... Electrical field stimulation has been shown to improve cardiac cell alignment and functional properties. In this study, neonatal rat cardiomyocytes were exposed to both long-term and short-term stimulation with the goal of investigating whether it is possible to achieve cell orientation and the maturation of cardiomyocytes with a novel, microelectrode array (MEA)-compatible electrical stimulation platform. Cells were viable after electrical stimulation, but no orientation or other morphological changes were observed. However, the electrode wires in MEA dishes affected the cell orientation. Cell contractions synchronized with pacing, but settled back to their original frequency in the absence of stimulation. The expression of genes encoding a gap junction protein connexin-43 (Cx-43), and contractile cardiac protein beta myosin heavy chain 7, was stronger in stimulated cells than in controls (p<0.05). In summary, the surface topography influenced to cardiomyocyte orientation, suggesting that the micro architecture of the biomaterials should be carefully designed for cell applications. However, as electrical stimulation and its duration affected gene expression of some main cardiac proteins, the stimulation system may prove useful to enhance the cardiac differentiation of stem cells.

In Vitro and In Vivo (1)H-MR Spectroscopic Examination of the Renal Cell Carcinoma.

Süllentrop F, Hahn J, Moka D

Int J Biomed Sci · 2012 Jun · PMID 23675262

BACKGROUND: Paraneoplastic effects are some of the major side effects of advanced renal cell carcinoma (RCC). Magnetic resonance spectroscopy (MRS) is known as a powerful tool to study cancer cell metabolism and cancer c... BACKGROUND: Paraneoplastic effects are some of the major side effects of advanced renal cell carcinoma (RCC). Magnetic resonance spectroscopy (MRS) is known as a powerful tool to study cancer cell metabolism and cancer cell - host interactions. Aim of this study was to assess tumor cell metabolism and systemic effects using (1)H-MRS. METHODS: Spectroscopic analysis of 10 patients with RCC was compared with those of 15 healthy volunteers. Local tumor metabolism was assessed using image-guided (1)H-in-vivo-spectroscopy in a 1.5 Tesla MR whole body tomograph. Systemic effects of RCC were measured using (1)H-High-Resolution (HR) spectra of blood plasma samples in a 500 MHz Bruker DRX 500 spectrometer. RESULTS: In-vivo-spectroscopy can significantly differentiate tumor tissue from healthy renal tissue by comparing their lipid composition. Moreover after detailed assignment of the various metabolites in blood plasma in the in-vitro-HR-spectra significant systemic alterations could be identified in patients with RCC especially regarding lipid and amino acid metabolism. CONCLUSION: This work indicates that using (1)H-MRS both changes in tumor metabolism and resulting systemic/paraneoplastic effects can be assessed in patients with RCC. This approach therefore offers scope for diagnosis and therapy evaluation.

The Excellent Anti-Tumour Strategy (CTGVT, OV-gene) and the Excellent Anti-Tumor Gene (IL-24).

Liu XY

Int J Biomed Sci · 2012 Jun · PMID 23675261

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