Köhn C, Dubrovska G, Huang Y
… +1 more, Gollasch M
Int J Biomed Sci
· 2012 Jun · PMID 23675260
Hydrogen sulfide is the "third" gasotransmitter on the rise in cardiovascular research. Recent studies show that hydrogen sulfide has a great potential in the regulation of vascular tone of systemic arteries and many mol...Hydrogen sulfide is the "third" gasotransmitter on the rise in cardiovascular research. Recent studies show that hydrogen sulfide has a great potential in the regulation of vascular tone of systemic arteries and many molecular targets are discussed. However, the complex mechanism of vascular tone regulation by hydrogen sulfide is only incompletely understood. It seems that a potent interaction of hydrogen sulfide with vascular endothelial growth factor (VEGF) becomes important in angiogenesis, in the process of wound healing, but also in tumor angiogenesis. Hydrogen sulfide exerts anti-inflammatory effects and it could be a pharmacological target in vascular dysfunction in association with obesity-related hypertension as well as in tumor development and progression. However, the underlying molecular pathways still need to be revealed. This review primarily focuses on the regulatory role of hydrogen sulfide in controlling vascular tone. We attempt to provide recent insights into mechanisms by which CSE-dependent hydrogen sulfide plays a role in the regulation of vascular tone by perivascular adipose tissue. The role of KCNQ channels and other ionic permeation pathways as key targets will be discussed. Recent findings which are summarized in this paper provide new insights into molecular mechanisms of hydrogen sulfide that are crucial for understanding vascular dysfunction in cardiovascular disease and possibly angiogenesis. Future research will be extended to investigate the therapeutic potential of hydrogen sulfide and their targets such as KCNQ channels in cardiovascular diseases, angiogenesis and tumor genesis.
A reliable technique is needed to determine the effect of ionizing radiation on white blood cell (WBC) counts. Facilities that utilize automated methods can provide this service. However, utilizing external facilities ca...A reliable technique is needed to determine the effect of ionizing radiation on white blood cell (WBC) counts. Facilities that utilize automated methods can provide this service. However, utilizing external facilities can introduce additional variables, such as differences between time of sample collection and time of sample processing, which may affect the results. The purpose of the present study was to determine whether an automated method at an external facility can accurately determine radiation-induced changes in total WBC, lymphocyte and granulocyte counts when samples are analyzed at periods of time up to 24 hours after collection and stored either at room temperature or at 4°C. To accomplish this, we compared automated blood cell counts determined at an external facility with our manual blood cell counts processed immediately after sample collection or 24 h after sample collection and stored either at room temperature or 4°C from mice exposed to 2 Gy proton or 2 Gy gamma radiation. Our results show a close correlation and good agreement between the two methods, indicating that neither a delay of 24 hours in sample processing nor storage temperature affected white blood cell counts. Analysis of the effects of radiation on blood cell counts by either manual or automated cell counts revealed a statistically significant decrease in lymphocyte and granulocyte counts at different days post-irradiation, with no statistically significant difference between the methods employed; therefore both manual and automated blood cell counts are reliable methods to determine the effects of ionizing radiation in blood cells.
Florento L, Matias R, Tuaño E
… +3 more, Santiago K, Dela Cruz F, Tuazon A
Int J Biomed Sci
· 2012 Mar · PMID 23675259
Chemotherapy is the main treatment modality for certain types of cancer. It is important to monitor and ensure that these chemotherapeutic drugs are potent and effective prior to patient administration. The objective of...Chemotherapy is the main treatment modality for certain types of cancer. It is important to monitor and ensure that these chemotherapeutic drugs are potent and effective prior to patient administration. The objective of the study is to evaluate the cytotoxic activity and potency of selected commercially available generic anticancer drugs in comparison with originator using various human cancer cell lines in an in vitro cell-based assay. Half-maximal inhibitory concentration (IC50) of the different chemotherapeutic agents was obtained from an experimentally derived dose-response curve. Relative potency of the drugs was estimated according to Parallel Line assay. This study demonstrated that the selected generic oncology products tested had similar efficacy compared with the originator. Both products showed comparable results as shown both in vitro cytotoxicity assay and statistical analysis. In vitro cell-based cytotoxicity assay promises to be a useful, reliable and rapid method for demonstrating chemotherapeutic drug activity.
Dwiranti F, Hiraoka M, Taguchi T
… +3 more, Konishi Y, Tominaga M, Tominaga A
Int J Biomed Sci
· 2012 Mar · PMID 23675258
We have studied edible algae that have the potential to down-regulate blood glucose. In Japan, Ecklonia species have been believed to improve the circulation of blood. In this study, we used leptin receptor deficient typ...We have studied edible algae that have the potential to down-regulate blood glucose. In Japan, Ecklonia species have been believed to improve the circulation of blood. In this study, we used leptin receptor deficient type 2 diabetes model mice (db/db) and prediabetic C57BL/6J mice. We also focused on the role of IFN-γ in the control of blood levels of triacylglycerol and glucose, because it is reportedly engaged in the regulation of energy consumption together with leptin. We report that gametophytes of Ecklonia kurome down-regulate the blood level of glucose and serum level of triacylglycerol in db/db. We also report that gametophytes of Ecklonia kurome down-regulate the level of glucose but not the level of triacylglycerol in prediabetic C57BL/6J mice induced by a high fat diet. They increased the level of triacylglycerol compared to that of control group in C57BL/6J, but not in IFN-γ KO mice. Gametophytes of Ecklonia kurome were administered orally to prediabetic C57BL/6J and IFN-γ KO mice and oral glucose tolerance tests were performed to evaluate the effects of algae. During the administration of the normal diet, we found a higher level of blood glucose in a glucose tolerance test of IFN-γ KO mice compared with that of C57BL/6J. Although a high fat diet induced a higher level of blood glucose compared with a normal diet group in a glucose tolerance test of C57BL/6J mice, this effect of high fat diet was not observed clearly at first but appeared three hours after glucose administration in IFN-γ KO mice. Gametophytes of Ecklonia kurome down-regulated the level of blood glucose in both C57BL/6J and IFN-γ KO mice, when administered a normal diet after making them prediabetic. These results suggest that Ecklonia kurome are effective to down-regulate the blood glucose and IFN-γ is involved in the regulation of blood glucose and triacylglycerol.
Bollig-Fischer A, Thakur A, Sun Y
… +2 more, Wu J, Liao DJ
Int J Biomed Sci
· 2012 Mar · PMID 23675257
There are many estrogen receptor α (ERα) antibodies available but few of them target a rodent ERα. Using the MC-20 antibody raised against the C-terminus of mouse ERα, we show in this communication that in the mammary gl...There are many estrogen receptor α (ERα) antibodies available but few of them target a rodent ERα. Using the MC-20 antibody raised against the C-terminus of mouse ERα, we show in this communication that in the mammary gland of female mice and rats, the wild type (wt) ERα was detected on immunoblots as a dominant protein only during lactation, and the protein was lactating specific as it migrated slightly faster than the 67-kD wt ERα in the uterus, likely due to a different phosphorylation status. In contrast, in the nulliparous, pregnant, involuting and involuted mammary glands, the dominant protein recognized by MC-20 was about 61-kD, which is dubbed herein as "MC-20 reactive protein" or MC20RP in abbreviation as its identity is unknown. Our results showed that it was not derived from proteolysis or de-phosphorylation of the 67-kD ERα and was unlikely to be translated from an ERα mRNA variant. Ovariectomy decreased the lactating specific wt ERα but increased the 61-kD MC20RP in the mammary tumors from MMTV-c-myc transgenic mice but these two proteins in the uterus were unaffected. The 61-kD MC20RP was decreased in the mammary tumors, compared with proliferating mammary glands, in estrogen-treated ACI rats. These results suggest that while the lactating specific wt ERα alone or together with the MC20RP may sustain lactation, the MC20RP may support proliferation of the mammary gland and some mammary tumors.
A novel economic procedure for the simultaneous stereospecific separation and analysis of (R)- and (S)-citalopram and its related substances or impurities has been developed and validated. Chromatography was performed on...A novel economic procedure for the simultaneous stereospecific separation and analysis of (R)- and (S)-citalopram and its related substances or impurities has been developed and validated. Chromatography was performed on silica gel 60 F254 plates with acetonitrile: methanol: water (15:2.5:2.5: v/v/v) as a mobile phase containing 1.5 mM norvancomycin or 2.5 mM vancomycin as a selector at ambient temperature. (R)- and (S)-citalopram enantiomers in presence of its related substances; citalopram citadiol and citalopram N-oxide were well separated with significant Rf values of 0.33 ± 0.02, 0.85 ± 0.02, 0.45 ± 0.02 and 0.22 ± 0.02, respectively. The spots were detected with either iodine vapor, or by use of a UV lamp followed by densitometric measurement at 239 nm. All variables affecting the resolution, such as concentration of chiral selectors, mobile phase system at different temperatures and pH-values were investigated and the conditions were optimized. Calibration plots for analysis of (R)- and (S)-enantiomers were linear in the range of 0.2-16.8 μg/10 μl (R≥0.9994, n=6) with acceptable precision (%RSD<2.0) and accuracy (99.70 ± 0.85% and 99.51 ± 0.61% for (S)-citalopram and escitalopram, respectively). The limit of detection and quantification were 0.08 μg/10 μl and 0.25 μg/10 μl, respectively, for (R)- and (S)-citalopram. The proposed method is simple, selective, and robust and can be applied for quantitative determination of enantiomeric purity of (R)- and (S)-citalopram (escitalopram) as well as the related impurities in drug substances and pharmaceutical preparations. The method can be useful to investigate adulteration of pure isomer with the cheep racemic form.
The γ(G)-158 (C→T) polymorphism plays important function in the disease severity of sickle cell anemia. The XmnI restriction site at -158 position of the γ(G)-gene is associated with increased expression of the γ(G)-glob...The γ(G)-158 (C→T) polymorphism plays important function in the disease severity of sickle cell anemia. The XmnI restriction site at -158 position of the γ(G)-gene is associated with increased expression of the γ(G)-globin gene and higher production of HbF. This study aims to determine the frequency of the different genotypes of the γ(G) Xmn I polymorphism in sickle cell anemia and sickle cell trait patients in Chhattisgarh and its association with high HbF level. The Xmn1 polymorphic site was determined by PCR-RFLP procedure. XmnI polymorphism were studied in 100 sickle cell patients (SS), 50 sickle cell trait (AS) and 50 controls individuals (AA). The presence of XmnI (+/+) site in SS and AS patients associated with the increase of HbF (P<0.0001) synthesis. we also find that presence of one XmnI (+/-) site in SS patients compared with XmnI-/- site had not shows difference in HbF level. Polymorphic association is found between presence and absence of XmnI site with HbF level, in AS and AA individuals.
Liu W, Zhang J, Ying C
… +7 more, Wang Q, Yan C, Jingyue Y, Zhaocai Y, Yan X, Heng-Jun S, Lin J
Int J Biomed Sci
· 2012 Mar · PMID 23675254
Lung cancer has the highest morbidity and mortality of any malignant tumor. To improve efficacy and reduce toxicity in patients with advanced non-small cell lung cancer (NSCLC), it is important to integrate traditional a...Lung cancer has the highest morbidity and mortality of any malignant tumor. To improve efficacy and reduce toxicity in patients with advanced non-small cell lung cancer (NSCLC), it is important to integrate traditional and conventional medicine. Two hundred and forty patients with advanced NSCLC were randomized to tetrandrine plus GP or GP only. We infused gemcitabine on days 1 and 8; cisplatin on day 1. The tetrandrine group received continuous i.v. infusion for 10 days, with treatment repeated every 21 days. After 2 consecutive treatment cycles, we used RECIST criteria to evaluate short-term efficacy. Quality of life (QOL) was assessed according to Karnofsky score (KPS) and body weight change. We used NCI CTC 3.0 to evaluate treatment toxicity. The short-term objective response rate was 36.1% in the tetrandrine group and 24.3% in the controls (P=0.057). The short-term disease control rate was 63.9% in the tetrandrine group and 52.3% in the controls (P=0.081). The 1-year survival rates were 45.7% and 31.3%, respectively (P=0.059). KPS scores improved by 49.1% and 32.4%, respectively (P=0.012). Body weight increased by 28.7% in the tetrandrine group and 16.2% in the controls (P=0.027). The incidence of grade 2-4 leukopenia, thrombocytopenia, nausea, and vomiting in the tetrandrine group was 38.0%, 19.4%, 46.3%, and 16.7%, respectively; the control group figures were 53.2%, 34.2%, 63.0% and 27.9% (P<0.05). Tetrandrine may improve short-term efficacy and survival in patients with advanced NSCLC. Tetrandrine may also mitigate adverse reactions to chemotherapy and improve QOL for patients with NSCLC.
BACKGROUND: Converting the two-dimensional (2D) cross-sectional photographs into an intuitive three-dimensional (3D) model is a basic task for medical imaging data for auxiliary disease-linked diagnosis purpose. METHODS:...BACKGROUND: Converting the two-dimensional (2D) cross-sectional photographs into an intuitive three-dimensional (3D) model is a basic task for medical imaging data for auxiliary disease-linked diagnosis purpose. METHODS: Reconstruction and visualization process of gastrointestinal cross-sectional photographs includes image preparation, image registration, image segmentation, 3D surface-rendering reconstruction, and implementation of 3D digital visualization. RESULTS: Using the visualization toolkit (VTK), we implemented 3D digital reconstruction and visualization of gastrointestinal tract, whose visualized model can be zoomed, paned, and rotated, including the stomach, the small intestine, and the large intestine.
Shawki MM, Elblbesy MA, Shalaby TE
… +2 more, Qotb MA, Youssef YS
Int J Biomed Sci
· 2012 Mar · PMID 23675252
The Electrochemotherapy (ECT) is an effective treatment of cutaneous and subcutaneous solid tumors. Electric field is applied to tumor nodules to enhance the delivery/distribution of a non-permeable or poorly permeable c...The Electrochemotherapy (ECT) is an effective treatment of cutaneous and subcutaneous solid tumors. Electric field is applied to tumor nodules to enhance the delivery/distribution of a non-permeable or poorly permeable chemotherapeutic agent into the tumor cells thereby increasing local concentration of anticancer drugs. The aim of this study was to evaluate the effectiveness of using two types of electric fields in ECT, pulsed sine waves and direct current (DC) application in addition to intra-tumoral injection of bleomycin (BLM), a cytotoxic drug for treating Ehrlich tumor. The electric fields were delivered through six stainless steel needle electrodes inserted into the tumor. Tumor volume, tumor mass, percentage of fragmented DNA in the tumor tissue, relative spleen mass/total body mass, mortality rate, histological and ultrastructural examinations were investigated in each group. There were 40% complete response (CR) and 60% partial response (PR) in the group treated with DC as the electric field source of ECT, while 0% (CR) and only 25% (PR) were found in the group treated with pulsed sine wave ECT. We concluded that the utilization of low dose DC for ECT gives better results than the low voltage pulsed sine waves in treating Ehrlich tumor which may be due to the dual effects of electrochemical reactions evoked by DC application and the anti-cancer activity of BLM.
Maus MK, Stephens C, Zeger G
… +2 more, Grimminger PP, Huang E
Int J Biomed Sci
· 2012 Mar · PMID 23675251
BACKGROUND: The discovery of the transforming fusion gene of the anaplastic lymphoma kinase (ALK) with the echinoderm microtubule-associated protein like 4 (EML4) as an oncogene in 2007 has led to its validation as a cli...BACKGROUND: The discovery of the transforming fusion gene of the anaplastic lymphoma kinase (ALK) with the echinoderm microtubule-associated protein like 4 (EML4) as an oncogene in 2007 has led to its validation as a clinical target in NSCLC patients in a short period of time. The inhibition of the anaplastic lymphoma receptor tyrosine kinase has demonstrated to prolong progression-free survival compared to the standard of care chemotherapy in patients with advanced NSCLC that are ALK positive. However, the clinical implications of the 15 different variants of the EML4-ALK transforming gene described so far are currently not defined. Here we present a novel variant of the EML4-ALK fusion gene which we named variant 3c. METHODS: RNA extracted from formalin fixed paraffin embedded (FFPE) specimens from patients with advanced and metastatic NSCLC was amplified, using primers and probes designed to detect specific EML4-ALK fusion gene fragments. Gel electrophoresis showed a different band for the new variant 3c compared to the known bands of positive cell lines for variant 3a and 3b. These findings were further investigated by dye-terminator Sequencing and FISH. RESULTS: The novel variant, detected in two NSCLC specimens, is longer than v3a and shorter than v3b, representing an 18 base pair insertion of intron 19 of ALK between exon 6 of EML4 and exon 20 of ALK. All of the two samples showed exactly the same sequencing result. One of the samples was negative for FISH break apart testing and the other one showed a positive result, defined by ≥15% split nuclei as indicative of an ALK rearrangement. CONCLUSIONS: Compared to FISH technology, RT-PCR enables the detection of different isoforms of the EML4-ALK transforming gene, which can be validated by sequencing. Only one out of two samples that were positive for the new variant by RT-PCR could be confirmed by FISH. The clinical significance of the different variants, notably to resistance and response to ALK-Inhibitors and the concordance and sensitivity of FISH and RT-PCR should be subject to further investigations.
Tamiru M, Hailemariam D, Mitike G
… +1 more, Haidar J
Int J Biomed Sci
· 2011 Dec · PMID 23675250
OBJECTIVE: To compare HIV-related sexual risk behavior among temporary rural to urban migrants and non-migrants and to explore the role of migration in HIV transmission in a rural area of Ethiopia. METHODS: A cross-secti...OBJECTIVE: To compare HIV-related sexual risk behavior among temporary rural to urban migrants and non-migrants and to explore the role of migration in HIV transmission in a rural area of Ethiopia. METHODS: A cross-sectional comparative study was conducted in Bure Woreda, West Gojam, Amhara Region, Ethiopia. A total of 1,310 male subjects (655 rural to urban migrants and 655 non-migrants) were selected randomly and were assessed, analyzed using SPSS version 17 software for their HIV related sexual risk behaviours including the role of migration in HIV transmission in a rural Ethiopia. Two parts of questionnaires were prepared and used for comparing the above groups. The first part of the questionnaires included non-sensitive questions such as demographics and HIV knowledge while the second part comprised sensitive questions related to sexual behaviors. RESULTS: When multiple sexual partners, sex with commercial sex workers, sexual transmitted infections and premarital sex compared between the two groups, the proportions of rural to urban migrants Vs non- migrants who had multiple sexual partners (31.4 % Vs 7.4 %), sex with commercial sex workers (22.3% Vs 13.3%), sexual transmitted infections (11.7% Vs 3.2%) and premarital sex (20.8% Vs 14.2 %) were significantly higher in rural to urban migrants than non-migrants. Among those who had multiple sexual partners, only 12.7 % of, rural to urban migrants and 9.8 % of non-migrants reported consistent condom use with sexual partners other than their spouse. CONCLUSIONS: As both rural to urban migrants and non-migrants are at risk for HIV infection, intervention programmes targeting both groups are recommended. However, in order to contain the bridging effect on HIV transmission from urban to rural areas particular attention should be given for the rural to urban migrant population.
Belal S, Abdel-Razak O, El-Walily AF
… +1 more, Bakry R
Int J Biomed Sci
· 2011 Dec · PMID 23675249
Two spectrophotmetric methods based on combined redox - ligand exchange reactions were developed for the determination of captopril and penicillamine in pure form and in their dosage forms. The first method is based on a...Two spectrophotmetric methods based on combined redox - ligand exchange reactions were developed for the determination of captopril and penicillamine in pure form and in their dosage forms. The first method is based on attenuating the absorbance of a ternary complex: silver (I) - bromopyrogallol red - phenanthroline in a buffer solution of pH6-8. The method has the concentration ranges 2-10 μg mL(-1) and 0.5-1.75 μg mL(-1) for captopril and penicillamine respectively, and the detection limits 7.1 × 10(-2) and 5.7 × 10(-2) μg mL(-1) for captopril and penicillamine respectively. The second method is based on decreasing the absorbance of a chloroformic solution of copper (II) - oxine chelate when shaken with the drug solution in buffer medium of pH 8. The drugs were determined in the concentrations 30-90 μg mL(-1) and 30-100 μg mL(-1) for captopril and penicillamine respectively, and the detection limits 0.94 and 1.76 μg mL(-1) for captopril and penicillamine respectively. The proposed methods were applied in the analysis of both compounds in their pharmaceutical preparations, and results were favorably compared with reference spectrophotometric methods regarding accuracy and precision.
A reversed-phase high-performance liquid chromatographic method was developed and validated for the determination of rosuvastatin calcium in pharmaceutical dosage forms. The determination was performed on a Nucleodur col...A reversed-phase high-performance liquid chromatographic method was developed and validated for the determination of rosuvastatin calcium in pharmaceutical dosage forms. The determination was performed on a Nucleodur column C8 (250 × 4.6 mm i.d., 5 μm particle size); the mobile phase consisted of a mixture of 0.1M formic acid and methanol (25:75, v/v), pumped at a flow rate 1.0 mL min(-1). The photodiode array detector was operated at 280 nm. The retention times for rosuvastatin and fluvastatin, which was used as internal standard, were 3.98 and 7.78 min, respectively. Linearity range (r (2) better than 0.999, n=6) was 3.0-1602.0 μg mL(-1) with limit of detection value of 0.12 μg mL(-1). The precision of the method was demonstrated using intra- and inter-day assay RSD% values which were less than 2.40%, while the recovery was 99.86-102.86%. The method was applied in the quality control of commercial tablets and content uniformity test and proved to be suitable for rapid and reliable quality control.
Villaamil VM, Gallego GA, Caínzos IS
… +3 more, Ruvira LV, Valladares-Ayerbes M, Aparicio LM
Int J Biomed Sci
· 2011 Dec · PMID 23675247
INTRODUCTION: Renal cell carcinoma is the most common type of kidney cancer. A better understanding of the critical pathways and interactions associated with alterations in renal function and renal tumour properties is r...INTRODUCTION: Renal cell carcinoma is the most common type of kidney cancer. A better understanding of the critical pathways and interactions associated with alterations in renal function and renal tumour properties is required. Our final goal is to combine the knowledge provided by a regulatory network with experimental observations provided by the dataset. METHODS: In this study, a systems biology approach was used, integrating immunohistochemistry protein expression profiles and protein interaction information with the STRING and MeV bioinformatics tools. A group consisting of 80 patients with renal cell carcinoma was studied. The expression of selected markers was assessed using tissue microarray technology on immunohistochemically stained slides. The immunohistochemical data of the molecular factors studied were analysed using a parametric statistical test, Pearson's correlation coefficient test. RESULTS: Bioinformatics analysis of tumour samples resulted in 2 protein networks. The first network consists of proteins involved in the angiogenesis pathway and the apoptosis suppressor, BCL2, and includes both positive and negative correlations. The second network shows a negative interaction between the p53 tumour suppressor protein and the glucose transporter type 4. CONCLUSION: The comprehensive pathway network will help us to realise the cooperative behaviours among pathways. Regulation of metabolic pathways is an important role of p53. The pathway involving the tumour suppressor gene p53 could regulate tumour angiogenesis. Further investigation of the proteins that interact with this pathway in this type of tumour may provide new strategies for cancer therapies to specifically inhibit the molecules that play crucial roles in tumour progression.
BACKGROUND: Speech-language pathologists/Otolaryngologists recognize high prevalence of speech and language disorder among children. The aim of the study is to find out the epidemiological profile of speech and language...BACKGROUND: Speech-language pathologists/Otolaryngologists recognize high prevalence of speech and language disorder among children. The aim of the study is to find out the epidemiological profile of speech and language disorder in north central Nigeria. METHOD: A five year retrospective review of all referral to speech and language therapy unit ENT Department between January 2005 and December 2009. Information retrieved and analysed included bio-data, clinical presentation and diagnosis of the patients. Descriptive analysis of these data were done. RESULTS: A total of 146 patients were seen out of which 89 (61%) were under five, 32 (21.9%) were between 5-10 years, 20 (13.7%) in the range of 11-20 yrs and 2 (1.4%) were between 21-34 yrs. None was observed in the elderly. Male preponderance was noted with male to female ratio of 1.9:1.0. The commonest diagnosis was deaf-mutism in 84 (57.5%) followed by delayed speech development in 31(21.2%) patients. The least diagnosis was aphasia in 2 (1.4%) patients. CONCLUSION: Speech and language disorder was commonest among the under five's with non in the elderly, There was a higher prevalence amongst males and deaf-mutism was the commonest observed.
Santos JL, Bosquesi PL, Almeida AE
… +2 more, Chin CM, Varanda EA
Int J Biomed Sci
· 2011 Dec · PMID 23675245
The hydroxyurea, a cytotoxic drug, is the mainly available therapeutical strategy for the treatment of sickle cell disease. This study aimed to evaluate the mutagenic and genotoxic potential of the hydroxyurea through th...The hydroxyurea, a cytotoxic drug, is the mainly available therapeutical strategy for the treatment of sickle cell disease. This study aimed to evaluate the mutagenic and genotoxic potential of the hydroxyurea through the Salmonella/Microsome assay and micronucleus test in peripheral blood of mice. The doses were evaluated at 29.25-468 μmol/plate in Salmonella/Microsome assay in presence and absence of metabolic activation the drug. In the micronucleus test the doses were evaluated at 12.5; 25; 50; 75 and 100 mg/kg. The results show that hydroxyurea present mutagenic activity in TA98 and TA100 in doses above 117 μmol/plate and 234 μmol/plate respectively. The drug induced a significant increase in the frequency of micronuclei in reticulocytes of mice at concentrations of 50, 75 and 100 mg/kg, compared to negative control (water). These results demonstrated the mutagenic and genotoxic potential of hydroxyurea.
Takehira R, Murakami K, Katayama S
… +2 more, Nishizawa K, Yamamura S
Int J Biomed Sci
· 2011 Dec · PMID 23675244
AIM: The purpose of this study was to investigate the difference between the professional perspectives of pharmacists and nurses in Japan with regard to evaluation of the quality of life (QOL) of cancer patients. METHODS...AIM: The purpose of this study was to investigate the difference between the professional perspectives of pharmacists and nurses in Japan with regard to evaluation of the quality of life (QOL) of cancer patients. METHODS: A group of cancer hospital inpatients (n=15) were asked to rate the condition of their health and their QOL by filling in a questionnaire. On the same day, a group of pharmacists (n=8) and nurses (n=18) also evaluated patient QOL. Three-layered artificial neural network (ANN) architecture was used to model the relationship between the different QOL evaluations made by patients, pharmacists, and nurses. RESULTS: Although there was no statistical difference between the QOL scores obtained from pharmacists and nurses, the correlation between these scores was weak (0.1188). These results suggest that pharmacists and nurses evaluate the QOL of their patients from different perspectives, based on their respective profession. QOL parameters were modeled with an ANN using the scores, given by patients in answer to questions regarding health-related QOL as input variables. Both the predictive performance of the ANN and the robustness of the optimized model were acceptable. The response surfaces calculated by ANN modeling showed that pharmacists and nurses evaluate patient's QOL using different information and reasoning, which is likely related to the nature of their contact with the patients. CONCLUSION: Health professionals evaluate patient QOL from different perspectives, depending on their profession.
To investigate the relationship between medical improvements and the survival experienced by the patient population, it would be useful to find out when and how much the cancer treatment breakthroughs and early diagnosis...To investigate the relationship between medical improvements and the survival experienced by the patient population, it would be useful to find out when and how much the cancer treatment breakthroughs and early diagnosis have significantly improved the prognosis of brain cancer patients. A join point model facilitates the identification of trends with significant change-points in survival; the main goal of such a model would be to find out when cancer survival starts exhibiting a pattern of improvement. The model will be applied to grouped relative survival data for major cancer sites from the 'Surveillance, epidemiology and end results' program of the National Cancer Institute.
This review aims to investigate the role of genetic changes in the development of cardiovascular diseases [CVD]. Oxidation of Low density Lipoprotein (LDL) and mutations in LDL receptors gene are a trigger for numerous o...This review aims to investigate the role of genetic changes in the development of cardiovascular diseases [CVD]. Oxidation of Low density Lipoprotein (LDL) and mutations in LDL receptors gene are a trigger for numerous of atherogenic events. Also, endothelial nitric oxide synthase (eNOS) plays an important role in vasodilatation of blood vessels through synthesis of nitric oxide. Three single base pair changes, 786T/C, 922A/G, and 1468T/A, have been identified in the promoter region of the eNOS gene and are associated with coronary spasm. Moreover, two distinct variable nucleotide tandem repeats (VNTRs) in introns 4 and 13 have been detected. The presence of a minimum of 38 CA repeats in intron 13 has been associated with an independent 2.2-fold increase in the risk of coronary artery disease [CAD]. Plasma glutathione peroxidase (GPx-3) maintains the vascular bioavailability of nitric oxide (NO), through depletion of reactive oxygen species. Mutation(s) or polymorphism(s) in the plasma GPx-3 gene promoter may predispose to a thrombotic disorder, and constitute a genetic risk factor for thrombotic cerebrovascular disease. Hyperhomocysteinemia is another independent risk factor for atherosclerosis and arterial thrombosis. Severe hyperhomocysteinemia could be caused by cystathionine-β-synthase enzyme deficiency but it could be due to homozygosity of a common 677C/T point mutation in the coding region of the methylenetetrahydrofolate reductase (MTHFR) gene as a 3-fold increase in risk of CAD is associated with the MTHFR 677TT genotype. A second common variant in MTHFR 1298A/C is associated with decreased enzyme activity in vitro and in vivo, especially when occurring simultaneously with the 677 C/T polymorphism. Elevated fibrinogen, an essential component of the coagulation system, has been most consistently associated with arterial thrombotic disorders. Several polymorphisms (148C/T, 455G/A, and -854G/A) have been identified in the genes encoding the 3 pairs of fibrinogen polypeptide chains. The -455G/A, and -854G/A substitutions are the most physiologically relevant mutations. In addition the -455A allele has been associated with the progression of atheroma, and also with a 2.5-fold increase in risk of multiple lacunar infarcts in a cohort of elderly patients with stroke. It is concluded that genetic changes in the previously mentioned genes could play a significant role in the initiation and progression of CVD. This review provides useful information for both physicians and medical students whom are interested in human genetics which is related to cardiovascular diseases.