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1.
It is clear that cancer is one of the most mortal diseases in the world and the most prevalent among women is breast cancer. As hydroxyurea (HU)—a drug which is used in chemotherapy—has many adverse effects in long-term despite of its therapeutic properties, we made use of nano drug delivery technology in order to reduce adverse effects and increase therapeutic index. Thus, liposomation is a novel way in drug delivery systems. In this study a mixture of phosphatidylcholine and cholesterol was mixed and HU was added to the resultant mixture. The mean diameter of the nanoliposomal HU measured with the Zeta Sizer device (equal to 402.5 nm) and its encapsulation efficiency was 70.8 %. Besides, using dialysis, the pattern of drug release from nanoliposomes has been studied and the results showed that the drug release of nanoliposomal drug within 28 h was equal to 25.85 %. This study showed that the cytotoxicity effect of nanoliposomal drug is more than that of the standard drug.  相似文献   

2.
Breast cancer is one of the most frequent cancer types within women population. Hydroxyurea (HU) is a chemotherapy compound for treatment of patients with cancer diagnosis, including breast cancer associated with several adverse effects. In this study, we applied nanotechnology to decreased drug side effects along with improvement of therapeutic index. Liposomation is widely used in modern pharmacological developments in order to enhance the effects of the drugs. To achieve this, in this study a mixture of phosphatidylcholine and cholesterol was made up and HU was added to the resultant mixture, was then pegylated using Polyethylene Glycol 2000 to increase resistance, applicability and solubility. The mean diameters of nanoliposomal and pegylated nanoliposomal HU were measured by Zeta sizer device and obtained about 402.5 and 338.2 nm. The efficiency of non-pegylated and pegylated liposomal HU was 70.8 and 64.2, respectively. Releasing HU in both formulations was estimated about 25.8 and 21.7 %. Also, this study investigated the cytotoxicity effect of nanoliposomal and pegylated nanoliposomal HU using MTT assay. Results of this investigation showed that the cytotoxic properties of pegylated HU was 3.6 % more than those non-pegylated form, while was 38.93 % more than ordinary from of HU. This study showed that the stability, releasing pattern and cytotoxicity of the pegylated nanoliposomal HU is better than that of nanoliposomal HU.  相似文献   

3.
Nano carriers have greatly revolutionized the treatment of most diseases recently. One of these nano carriers, liposomes, has got particular significance. On the other hand, Artemisinin which is used as an effective anticancer drug has some side effects. To reduce such side effects, liposomes can be employed. In order to prepare pegylated nanoliposomal artemisinin, particular proportions of phosphatidylcholine, polyethylene glycol 2000 and artemisinin were combined. As a result, the mean diameter of nano liposomes is 455 nm. Besides, the encapsulation efficiency and the drug release from pegylated nanoliposomes for pegylated nanoliposomal artemisinin are respectively 91.62 ± 3.5 and 5.17 %. The results also show that IC50 of the produced formulation is less than that of the standard drug. This study reveals that the amount of artemisinin cytotoxicity compared to standard drug is increased by pegylated nanoliposomal formulation.  相似文献   

4.
In the present study, paclitaxel was archaeosomed to reduce side effects and improve its therapeutic index. Carriers have made a big evolution in treatment of many diseases in recent years. Lipid carriers are of special importance among carriers. Archaeosome is one of the lipid carriers. Paclitaxel is one of the drugs used to treat breast cancer which has some unwanted side effects despite its therapeutic effects. Archaeosomes were extracted from methanogenic archi bacteria and synthesized with a certain ratio of paclitaxel in PBS. The mean diameter of archaeosomal paclitaxel was measured by Zeta sizer instrument, Drug releasing of archaeosomal paclitaxel was examined within 26 h which results showed that the most drug releasing occurs during first 3 h. The cytotoxicity effect of archaeosomal paclitaxel on breast cancer’s cell line was evaluated by MTT assay which results showed that the cytotoxicity effect of archaeosomal paclitaxel on breast cancer’s cell line is more than that of the standard paclitaxel formulation. The results indicated that new drug delivery of paclitaxel using archaeosome, increases the therapeutic index of the drug.  相似文献   

5.
This study is aimed to investigate the nanoliposomal artemisinin preparation, and its implementation on breast cancer cells. Side effects have been one of the common challenges of drug usage, as well as cancer treatment. In order to reduce such effects, nanotechnology has been a great help. Nanoliposomes are provided through reverse phase evaporation. In this method, certain proportions of phosphatidylcholine, cholesterol and artemisinin were mixed together. Besides, the obtained formulation was pegylated by using polyethylene glycol 2000 in order to increase its stability and solubility. The mean diameter of non-pegylated and pegylated liposomal artemisinin was determined by Zeta sizer system. The percent of drug released from liposome was performed by dialysis. The encapsulation efficiency of both formulations was estimated by spectrophotometry method. As a result, encapsulation and drug release of nanoliposomal formulation were more than the pegylation of the same formulation. In addition, this study indicated that cytotoxicity effect of pegylated nanoliposomal artemisinin was more, in comparison with nanoliposomal artemisinin.  相似文献   

6.
Voriconazole, an antifungal drug exhibiting wide inter-individual variability, is an ideal candidate for therapeutic drug monitoring (TDM). The aim of the present study was to standardize a simple, sensitive and rapid high performance liquid chromatography (HPLC) method with ultraviolet detection to determine plasma voriconazole concentration. The HPLC method consisted of a combination of acetonitrile and water (7:3) as mobile phase with 1 ml/min flow rate and detection at 255 nm. Plasma protein precipitation was carried out using perchloric acid and the filtered supernatant was passed through C18 column (250 × 4.6 mm, 5 μm) for the separation of voriconazole. The limit of quantification of voriconazole was 0.2 mg/L. The assay was validated with a linearity of 0.2–15 mg/L and used clinically for TDM in patient samples. The inter-assay precision was below 15 % for routine quality control samples. Weight based voriconazole doses were prescribed to 26 patients for empirical treatment of invasive fungal infections. Voriconazole therapy was managed from the baseline drug levels and follow up analysis reflected achievement in clinical efficacy. Routine TDM of voriconazole may reduce adverse events and improve the treatment response in invasive fungal infections.  相似文献   

7.
Cisplatinum (Cispt) is an anti-cancer drug with a low level of solubility. One of Cispt’s solvents is dimethyl sulfoxide (DMSO) which can be substituted with chlorine of drug as Cispt’s solvent. Applying such a solvent in biological studies is impossible due to intense reduction in activity. On the other hand, it is specified that Cispt’s stability is increased in aqueous media by increasing sodium chloride (NaCl) concentration up to 0.9 %. Consequently, we intended to study the effect of DMSO on cytotoxicity of Cispt in presence of sodium. MTT assay was employed to study cytotoxicity effect of Cispt + NaCl + DMSO and Cispt + DMSO on G-292 cell line. Cytotoxicity in dilutions of 300 and 9 (p < 0.01) of Cispt in Cispt + NaCl + DMSO formulation was equal to 78 and 7 %. These values were estimated 79 and 18 % for Cispt + DMSO formulation and 79 and 24 % for free drug. IC50 values demonstrated reduction of 45 % in cytotoxicity of Cispt in Cispt + DMSO formulation. Studying chemical structure of Cispt and Cispt dissolved in DMSO showed that NaCl cannot inhibit inactivating effect of DMSO on Cispt and effect of this solvent on Cispt is independent from presence of NaCl. Results represented that using NaCl does not result in stability and keeping cytotoxicity properties of Cispt in DMSO. Findings suggest more studies for using DMSO as a solvent of Cispt.  相似文献   

8.
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9.
The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to Alzheimers disease (AD) was controversial in previous studies. The present meta-analysis was designed to investigate the association of MTHFR C677T polymorphism with AD. Nine studies were identified by search of PubMed, Google Scholar, Elsevier, Springer Link databases, up to January 2013. Odds ratios (ORs) with corresponding 95 % confidence interval (CI) were calculated using fixed effects model or random effects model. All statistical analysis was done by Mix version 1.7. MTHFR C677T polymorphism had a significant association with susceptibility to AD in all genetic models (for T vs C: OR 1.29, 95 % CI 1.15–1.44, p < 0.0001; for TT + CT vs CC: OR 1.38, 95 % CI 1.16–1.364, p = 0.0002; for TT vs CC: OR 1.60, 95 % CI 1.25–2.04, p = 0.0001; for CT vs CC: OR 1.28, 95 % CI 1.1–1.53, p < 0.008; for TT vs CT + CC: OR 1.37, 95 % CI 1.12–1.67, p = 0.002). Results from present meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of AD in Asian population.  相似文献   

10.
Non-alcoholic fatty liver disease shares many features of metabolic syndrome and its presence could signify a substantial cardiovascular risk above and beyond that conferred by individual risk factors. This study is an attempt to investigate the association of non-alcoholic fatty liver disease with carotid intima-media thickness and plaque as surrogate measures of increased cardiovascular risk. The study was conducted on 645 non diabetic, non alcoholic subjects in the age range of 20–60 years. Metabolic syndrome was assessed by using ATP III and ADA (2005) criteria. Anthropometric factors—waist circumference and blood pressure were measured. Fasting serum samples were analyzed for glucose, triglyceride, cholesterol and its fractions, insulin, alanine and aspartate transaminases, gamma glutamyl transferase and free fatty acids. Insulin resistance and secretion were calculated by homeostasis model and insulin sensitivity by QUICKI index. Liver ultrasonographic scanning was used for assessing fatty liver. Carotid atherosclerosis was assessed by B-mode ultrasonography of common carotid artery and internal carotid artery. The prevalence of non-alcoholic fatty liver disease was 15.6 % in non alcoholic population and 68.5 % of non-alcoholic fatty liver disease had metabolic syndrome, which was associated with hyperinsulinemia, insulin resistance, insulin insensitivity along with elevated levels of waist circumference, blood pressure, triglyceride, FFA and decreased HDL cholesterol. NAFLD patients had markedly greater carotid intima media thickness than non NAFLD subjects with MCIMT of 591.6 ± 108 and 489.5 ± 132.4 μm (P < 0.001) and plaque prevalence of 19.2 and 2.2 %, respectively, thus the carotid intima media thickness is associated with NAFLD.  相似文献   

11.
Carboplatin is a chemotherapeutic agent used against various malignancies such as ovarian carcinoma. The aim of this study is to improve the therapeutic efficacy of carboplatin using pegylated liposomal nanocarriers. Nanoparticles were synthesized using thin film hydration technique and characterized for shape morphology, particle size, zeta potential and drug-release properties. In the next step, A2780S and A2780CP ovarian cancer cell lines were used to determine the efficacy of nanodrug by MTT assay. The particle size and zeta potential of nanodrug were measured 244.3 ± 19.6 nm and ?22.9 ± 1.7 mV, respectively. High encapsulation capacity (78.6 ± 3.7 %) confirmed the efficiency of technique. The cytotoxicity results also showed that nanodrug compared to free drug improve the efficacy of carboplatin against both A2780S (P < 0.01) and A2780CP (P < 0.05) cell lines. In conclusion, the findings of our study suggested pegylated liposomal nanocarriers are proper for carboplatin delivery to ovarian cancer cell lines A2780S and A2780CP.  相似文献   

12.
Schizophrenia is a psychotic disorder with a complex pathophysiology and requires treatment that includes long term administration of antipsychotics that is said to be associated with metabolic syndrome. This study was designed to evaluate the impact of seven different antipsychotics prescribed to schizophrenic patients, on development of metabolic syndrome in the patients. A total of 210 patients with schizophrenia (30 patients in each drug therapy group) were recruited according to ICD-10 criteria and were assigned to receive the drug for 16 weeks. Measurement of anthropometric (body weight, waist circumference, blood pressure) and biochemical parameters (glucose, insulin, HOMA-IR, triglycerides, LDL, HDL) was done and the patients were subjected to ATP-III defined criteria for metabolic syndrome. Patients undergoing treatment with olanzapine were more prone to metabolic syndrome as the drug induces weight gain after 16 weeks of treatment. It also induces dyslipidemia (P < 0.001) and hyperglycemia (P < 0.01). Clozapine was found to be second most potent drug in inducing metabolic syndrome as the weight in clozapine treated patients increased after 16 weeks, along with a significant increase in glycemic (P < 0.001) and lipid parameters (P < 0.01). Aripriazole and amisulphride are comparatively safer drugs as their role in inducing metabolic abnormalities in schizophrenic patients was insignificant, although the impact of long term administration of these drugs needs to be explored. It is clear from the study that antipsychotic treatment induces metabolic syndrome so, it becomes important that the metabolic and cardiovascular risk factors should be surveillance regularly in schizophrenic patients undergoing antipsychotic treatment.  相似文献   

13.
It is well known that chronic exposure of lead leads to adverse health effects. Workers for plastic industry are generally exposed to high concentration of lead as fume, dust, and additive that protect PVC. This study was done on them to find out the detrimental effects of chronic lead exposure on hepatic and hematological toxicity. Blood and 24 h urine sample was collected from 47 plastic industry workers and matched against 42 controls for various parameters. The study group shows significant increase in blood (p < 0.0001) and urinary level of lead (p < 0.0001). Hemoglobin levels were significantly decreased (p < 0.0001), and the liver enzymes like ALP, ALT, AST and y-GT were significantly increased (p < 0.0001) in all cases exposed for >10 years. Serum lipid peroxide by quantitative assay of thiobarbituric acid reactive substances was also found increased in the study group (p < 0.0001). The observations point towards the acute health risk faced by plastic industry workers, in whom chronic exposure to lead increases the absorption and accumulation, over a period of time, of this highly toxic element in their body. This increases oxidative stress, causes metabolic damage to RBC and cell membranes, and also suggests necrosis of liver cell, hepatocellular injury and presence of space occupying lesions. Considering the data immediate health and hygiene monitoring and proper rehabilitation for the suffering population seem to be of paramount need in plastic industry to minimize occupational hazards.  相似文献   

14.
We aimed to assess whether measuring carotid intima-media thickness (CIMT) and oxidative stress markers such as protein carbonyls, malondialdehyde, nitrate and glutathione in plasma of elderly patients without and with coronary artery disease (CAD) identifies early risk for CAD. A total of 50 cases with cardiovascular risk factors over the age of 60 years without CAD, and 50 patients with angiographically documented CAD over the age of 60 years were included in the study. Control group consists of 200 healthy individuals without the risk factors. Demographic details were obtained from all the subjects and CIMT measured by high frequency ultrasound and oxidative stress markers such protein carbonyls, malondialdehyde and total glutathione were determined in plasma by spectrophotometric methods. The distribution of cardiovascular risk factors in without CAD and CAD cases were smokers (16 vs 56 %), hypertension (26 vs 64 %), diabetes (16 vs 56 %) and dyslipidemia (18 vs 58 %) and positive family history (4 vs 38 %). None of the control group had any cardiovascular risk factors. Among the CAD cases, 16 % had single vessel disease, 44 % had double vessel disease and 40 % had triple vessel disease. The CIMT was significantly increased in CAD cases as compared to cases without CAD and healthy controls. On the other hand, CIMT was significantly increased in cases without CAD as compared to healthy controls. CIMT also increased with the duration of diabetes in patients without CAD and severity of disease in CAD cases. The levels of oxidants like plasma malondialdehyde, protein carbonyls, were significantly elevated and antioxidant glutathione levels and nitrate levels were significantly reduced in cases with and without CAD as compared to healthy controls. Oxidative stress markers and CIMT was found to be significantly increased in patients with cardiovascular risk factors like diabetes, family history of CAD, dyslipidemia, hypertension and smoking when compared to patients without risk factors. In patients with diabetes, CIMT increased as duration of disease increases and also in poorly controlled diabetes. In CAD group, when number of vessel involvement (severity of coronary disease) increases, the CIMT also increases confirming that CIMT is a quantifiable risk factor for CAD.  相似文献   

15.
Traditionally small intestinal biopsy has been considered a gold standard for the diagnosis of celiac disease (CD). But now data has shown that serological markers like anti-tissue-transglutaminase antibodies (tTGA) can be used to make the diagnosis with great sensitivity and specificity. The objective of the present study was to evaluate whether patients with high probability of CD and high titre of tTGA, have a high probability of intestinal damage and may not require biopsy for final diagnosis. All the cases with tTGA levels ≥15 IU/ml and who subsequently underwent biopsy from July 2010 to June 2013 were selected. Histopathological findings graded as per Marsh classification were correlated with serum tTGA levels. Grade 3 lesions were considered diagnostic for the disease. Out of total 731 patients 470 had serum tTGA levels >100 IU/ml and 261 patients had <100 IU/ml. Highest levels of tTGA (219.3 IU/ml) were seen in grade 3c which was >12 times the normal cutoff value. Mean serum tTGA in higher histological grade i.e. 3 (3a, 3b, 3c) was 186.7 IU/ml (>12 times the normal cut off value) as compared to grade 1 which was 108.9 IU/ml (>7 times the normal cut off value). Using a tTGA cutoff value of 70 IU/ml, sensitivity was found to be 83.9% while specificity was 56.10% with an overall accuracy of 77.7%. This study confirms that a small intestinal biopsy is not always necessary for the diagnosis of CD in symptomatic patients with high tTGA levels (>70 IU/ml).  相似文献   

16.
The early diagnosis of bladder cancer is important for effective treatment of the disease. This study aimed to evaluate the nuclear matrix protein 22 (NMP 22), soluble epithelial cadherin (E-cadherin), cathepthin-D and total protein with clinico-pathological features of bladder cancer, and to determine the relation between each marker and tumor progression after treatment. The study includes 65 patients with bladder cancer, 14 benign urinary diseases and 11 healthy volunteers. Patients were categorized according to bilharzial infestation, T stage, tumor grade, size and the presence of lymph node metastasis. Forty patients were followed for disease progression after surgery. There was a significant increase of NMP22, E-cadherin, cathepthin-D and total protein detected in cancer group compared to healthy and benign groups. It was found that NMP 22 and E-cadherin had highest sensitivity (84.4, 76.9 %, respectively) while, total ddedprotein showed highest specificity (77.4 %). Tumor size correlated with urinary NMP22 (r = 0.3, p = 0.02), although, E-cadherin, cathepsin-D and total protein correlated with tumor size (r = 0.3, 0.28, 0.2; p = 0.01, p = 0.01, 0.04, respectively) and lymph node metastasis (r = 0.32, 0.34, 0.2; p = 0.003, 0.005, 0.04, respectively). Elevated pretreatment urinary NMP22, E-cadherin and total protein levels was associated significantly with bladder cancer recurrence (p = 0.02, 0.001, 0.005, respectively). In conclusion, determination of urinary NMP22, E-cadherin and total protein in bladder cancer patients or persons at risk of developing bladder cancer will help in early detection of the disease and prediction of recurrence. The use of a combination of tumor markers is markedly useful than the assessment of single one.  相似文献   

17.
Hemodynamically significant ductus arteriosus (hsPDA) may alter organ perfusion by interfering blood flow to the tissues. Therefore, in infants with hsPDA, hypoxia occurs in many tissues. In this study, we aimed to investigate the diagnostic significance of serum (ischemia-modified albumin) IMA levels as a screening tool for hsPDA, and its relation to the severity of the disease in the preterm neonates. For this purpose, seventy-two premature infants with gestation age <34 weeks were included in the study. Thirty premature infants with hsPDA were assigned as the study group and 42 premature infants without PDA were determined as the control group. Blood samples were collected before the treatment and 24 h after the treatment, and analyzed for IMA levels. IMA levels in the study group (1.26 ± 0.36 ABSU) were found to be significantly higher than control group (0.65 ± 0.12 ABSU) (p < 0.05). In infants with hsPDA, a positive correlation was found between IMA and PDA diameter (ρ = 0.876, p = 0.022), and LA/Ao ratio (ρ = 0.863, p = 0.014). The cut-off value of IMA for hsPDA was measured as 0.78 ABSU with 88.89 % sensitivity, and 90.24 % specificity, 85.71 % positive predictive, 92.5 % negative predictive value [area under the curve (AUC) = 0.96; p < 0.001]. The mean IMA value of the infants with hsPDA before treatment was 1.26 ± 0.36 ABSU, and the mean IMA value of infants after medical treatment was 0.67 ± 0.27 ABSU (p = 0.03). We concluded that IMA can be used as a marker for the diagnosis and monitoring of a successful treatment of hsPDA.  相似文献   

18.
Ankylosing spondylitis is a chronic inflammatory disease that has been linked to the human leukocyte antigen class I allele HLA-B27. More than 90 % of patients with ankylosing spondylitis possess the HLA-B27 allele, but only 1 % of people with HLA-B27 develop the disease. Ankylosing spondylitis predominately affects young males. The present study was planned to find out the involvement of HLA-B27 specific allele in relation to age and sex in symptomatic suspected patients of ankylosing spondylitis using conventional PCR technology. Forty symptomatic patients of ankylosing spondylitis were included in the present study. SSP–PCR technique was used to detect the HLA-B27 specific allele. This study showed (out of 40 symptomatic suspected cases of ankylosing spondylitis only 12 patients were detected positive with HLA-B27 allele, while remaining 28 were negative) that the positivity rate for ankylosing spondylitis with HLA-B27 allele is low. Furthermore, it was observed that the males above 50 years are more prone to develop AS with HLA-B27 specific allele. It could be concluded that the conventional PCR technology is a rapid, sensitive, and confirmatory method for the diagnosis of ankylosing spondylitis.  相似文献   

19.
Myasthenia gravis (MG) is an autoimmune disease that results from antibody mediated damage of Acetylcholine receptor (AChR) at the neuromuscular junction. The autoimmune character of MG and pathogenic role of AChR antibodies have been established by several workers i.e., the demonstration of anti-AChR antibodies in about 90 % of MG patients. It has been demonstrated that patients with MG also have antibodies against a second protein named presynaptic membrane receptor (PsmR), which is identified by utilizing β-Bgtx, a ligand which binds to PsmR. Using β-Bgtx Sepharose 4B affinity matrix, the PsmR was purified from different regions of human cadaver brain by affinity chromatography. Purified receptor was characterized both by biochemical and immunological procedures. PsmR purified from different regions of the brain shows a specific activity of 0.37 ± 0.01, 0.39 ± 0.02 and 0.43 ± 0.005 nM/ μg of protein in Parietal lobe, Occipital lobe and Frontal lobe respectively. The affinity purified PsmR from the brain of 87 and 68 kd (parietal lobe, occipital lobe and frontal lobe) shows immunoreactivity with myasthenic sera. These findings suggest that PsmR from brain is another antigen against which autoantibodies are developed in Myasthenia gravis patients. Upon treatment with various enzymes we concluded that PsmR from brain is a glycoprotein in which the immunoreactivity resides in the carbohydrate as well as the peptide epitopes. In conclusion the PsmR is another antigen against which autoantibodies are formed in different regions of brain. These can be used as a diagnostic tool for detecting antibodies in the sera or cerebrospinal fluid of MG patients.  相似文献   

20.
Traditionally Friedewald formula has been used to calculate low density lipoprotein cholesterol (LDL-C) concentration though now direct homogenous methods for its measurement are also available. Clinical guidelines recommend the use of calculated LDL-C to guide therapy because the evidence base for cholesterol management is derived almost exclusively from trials that use calculated LDL, with direct measurement of LDL-C being reserved for those patients who are non fasting or with significant hypertriglyceridemia. In this study our aim was to compare calculated and direct LDL and their variation at different cholesterol and triglyceride levels. Fasting lipid profile estimation was done on 503 outpatients in a tertiary hospital. Both direct and calculated LDL were then compared. Mean fasting direct LDL was found to be higher than calculated LDL in 87.1 % of subjects by 8.64 ± 8.35 mg/dl. This difference was seen a all levels of cholesterol and triglyceride. Using 130 mg/dl LDL cholesterol as cut off fewer subjects were classified as high risk by calculated LDL than direct LDL. In conclusion, direct LDL is higher than calculated LDL. Compared with direct measurement, the Friedewald calculation underestimates the risk for ischemic heart disease.  相似文献   

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