Cytotoxicity evaluation of environmentally friendly synthesis Copper/Zinc bimetallic nanoparticles on MCF-7 cancer cells.

Bimetallic nanoparticles offer unique chemical, physical and optical properties that are not available for monometallic nanoparticles. Bimetallic nanoparticles play a major role in various therapeutic, industrial and energy fields. Recently, nanoparticles of Copper/Zinc bimetallic nanoparticles have attracted attention in various fields, especially medicine. In this study, bimetallic CuO/ZnO nanostructures were biosynthesized using plant extracts. The plant-mediated synthesis nanoparticles were characterized by Transmission electron microscopy (TEM), X-ray diffraction analysis (XRD), Field Emission Scanning Electron Microscopy (FESEM) and Energy-Dispersive Spectroscopy (EDAX). The cytotoxicity of plant-mediated synthesis bimetallic nanoparticles and the synergistic effects of these nanoparticles in combination with the anticancer drug doxorubicin on MCF-7 cancer cells were evaluated by MTT assay.

Detection of novel mitochondrial mutations in cytochrome C oxidase subunit 1 (COX1) in patients with familial adenomatous polyposis (FAP).

BACKGROUND: Familial adenomatous polyposis (FAP) is an Autosomal dominant inherited disorder and a rare form| of colorectal cancer (CRC) that is characterized by the development of hundreds to thousands of adenomas in the rectum and colon. Mostly, cancers develop after the advent of the polyps. It appears in both sexes evenly, and the occurrence of the disease is in the second decade of life. Mitochondrial genome mutations have been reported with a variety of Tumors, but the precise role of these mutations in the pathogenicity and tumor progression is not exactly clear. Cytochrome c oxidase subunit I (COX1) is the terminal enzyme of the mitochondrial respiratory chain. The present study aims at assessing the occurrence of mtDNA mutations in COX1 gene in FAP patients and attempts to find out the cause and effect relationship between mitochondrial mutations and tumor progression. METHODS: In this study, 56 FAP patients were investigated for the presence of the mutations in mitochondrial COX1 coding gene by PCR and sequencing analysis. All sequences that differed from the revised Cambridge Reference Sequence (rCRS) were classified as missense/ nonsense or silent mutations. Functional genomic studies using Bio-informatics tools were performed on the founded mutations to understand the downstream alterations in structure and function of protein. RESULTS: We identified 38 changes in the COX1 gene in patients with FAP symptoms. Most of them were heteroplasmic changes of missense type (25/38). Tree of the changes (G6145A, C6988A, and T7306G) were nonsense mutations and had not been reported in the literature before. Our results of bioinformatics predictions showed that the identified mutations can affect mitochondrial functions, especially if the conservative domain of the protein is concerned. CONCLUSION: Our findings indicate a high frequency of mtDNA mutations in all of the FAP cases compared to matched controls. These data significantly enhance our understanding of how such mutations contribute to cancer pathologies and develop the cancer treatment methods by new diagnostic biomarkers, and new drugs for gene therapy.

Clinical and laboratory evaluation of cured and non-cured patients with cutaneous leishmaniasis treated by Glucantime.

BACKGROUND & OBJECTIVES: Insufficient treatment of cutaneous leishmaniasis (CL) by conventional drugs is a major barrier in control strategies. This study was aimed to evaluate Glucantime efficacy and the susceptibility of Glucantime unresponsive and responsive CL isolates in the field and laboratory. METHODS: Chi-square test (x[2]) was used to determine the significance of difference between proportions in Glucantime-treated patients. The inhibitory activity of various concentrations of Glucantime against Leishmenia tropica stages was evaluated by a colorimetric cell viability MTT and macrophage assays. Mixed model, t-test and ANOVA were performed to determine the significance of difference between various concentrations of Glucantime unresponsive or responsive isolates and untreated control group and p <0.05 was defined as significant level. Altogether, 89.8% of the patients were cured by Glucantime, whilst 10.2% remained non-cured. RESULTS: The overall Glucantime efficacy in different age groups and genders was similar. The IC50 values of promastigotes and amastigotes for Glucanime unresponsive isolates were 2.1 and 2.6 times higher than the equivalent rates obtained for responsive cases, respectively. The overall mean number of amastigotes within macrophages in unresponsive isolates was significantly higher (32.68 ± 1.24) than that in responsive ones (18.68 ± 1.52, p <0.001). Glucantime unresponsive and responsive field isolates of anthroponotic CL (ACL) caused by L. tropica strongly correlated to in vitro assays. INTERPRETATION & CONCLUSION: Monitoring of Glucantime unresponsiveness by the health surveillance system is extremely important, where anthroponotic transmission occurs in humans. Hence, physicians should be aware of such clinical unresponsive presentations with ACL for antimonial therapeutic failure to improve management of disease in endemic regions.

Evaluation of a self-nanoemulsifying docetaxel delivery system.

A self-nanoemulsifying drug delivery system (SNEDDS) was developed as a novel route to enhance the efficacy of docetaxel lipophilic drug. SNEDDS comprised ethyl oleate, Tween 80 and poly(ethylene glycol) 600, as oil, surfactant and co-surfactant, and formed stabilized monodispersed oil nanodroplets upon dilution in water. SNEDDS represented encapsulation efficiency and loading capacity of 21.4 and 52.7%, respectively. The docetaxel release profile from the drug-loaded SNEDDS was recorded, its effectiveness against MCF-7 cell line was investigated, and an IC50 value of 0.98 ± 0.05 µg mL-1 was attained. The drug-loaded SNEDDS was administrated in rats, and the pharmacokinetic parameters of maximum concentration of 22.2 ± 0.8 µg mL-1, time to attain this maximum concentration of 230 min, and area under the curve of 1.71 ± 0.18 µg min mL-1 were obtained. The developed SNEDDS formulation can be represented as an alternative to docetaxel administration.

Tacrolimus interaction with oral oestrogen in kidney transplant recipients: A case-control study.

WHAT IS KNOWN AND OBJECTIVE: Oestrogens could inhibit the metabolism of drugs, such as calcineurin inhibitors, that are substrates for cytochrome P-450 microsomal enzymes. This study assessed the potential tacrolimus interaction with oral conjugated oestrogen in kidney transplant recipients who received conjugated oestrogen as prophylaxis against bleeding, before kidney biopsy. METHODS: In this case-control study, 13 kidney transplant recipients who received oral conjugated oestrogen as prophylaxis against uraemic bleeding before allograft biopsy were considered as cases. Thirteen matched kidney transplant recipients with similar immunosuppressive regimen served as controls. In this study, comparisons were made between the groups regarding daily dose, blood trough concentrations and calculated concentration corrected for dose of tacrolimus at three time points of the study. RESULTS AND DISCUSSION: All patients in the case group received conjugated oestrogen at a dose of 3.75 mg/day for 4.78 ± 0.83 days. Without any change in tacrolimus dose, the blood concentration of tacrolimus increased during concomitant administration of conjugated oestrogen (from 8.10 ± 2.85 to 12.35 ± 4.62 ng/mL; P = .11) and decreased after cessation of conjugated oestrogen (6.07 ± 2.18 ng/mL; P = .015). The calculated concentration corrected for dose of tacrolimus increased from 127.04 ± 79.23 to 211.40 ± 146.38 ngmLmgkg/d after conjugated oestrogen administration (P = .036). Thereafter, it decreased to 108.55 ± 78.61 ngmLmgkg/d after cessation of oestrogen (P = .003). Only one patient experienced nausea while taking oestrogen without any change in her liver enzymes. WHAT IS NEW AND CONCLUSION: Concomitant administration of oral oestrogen increased tacrolimus blood concentration. Hence, it is necessary to monitor tacrolimus blood levels during concomitant oestrogen therapy and for several days after oestrogen withdrawal.

Carotid intima-media thickness as a marker of atherosclerosis in hemodialysis patients.

Atherosclerotic changes in carotid arteries of hemodialysis (HD) patients reflect global atherosclerotic changes in vasculature. Carotid intima-media thickness (CIMT) can be used for atherosclerosis prediction and assessment of cardiovascular risks in HD patients, and thus screening high-risk patients. In this cross-sectional study, CIMT was measured using ultrasonography (B-mode with 5-10-MHz multifrequency linear probe) in HD patients in our hospitals. Additionally, we assessed the relationship between their CIMT and some cardiovascular risk factors. A total of 62 HD patients (64.5% male) were included. Age, body mass index, low-density lipoprotein, fasting blood sugar, history of diabetes mellitus and cardiovascular disease, serum albumin, and duration and adequacy of HD in study patients had significant association with their CIMT. There were no significant relationships between CIMT and patient's gender, smoking, serum calcium, phosphate, calcium x phosphate product, hemoglobin, and uric acid level. More diagnostic modalities must be performed for detecting the impact of atherosclerosis on HD patients with high CIMT.

The role of neutrophil-gelatinase-associated lipocalin in early diagnosis of contrast nephropathy.

Neutrophil-gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury. The aim of this study was to define a cut-off for NGAL in the early diagnosis of contrast-induced nephropathy (CIN) in patients with normal kidney function. We enrolled 121 patients with normal serum creatinine who underwent coronary angiography. NGAL was measured in urine before the procedure and 12 and 24 h afterward. CIN was defined as a 0.3 mg/dl increase in serum creatinine within 48 h after the procedure. Seven of 121 patients had CIN (5.8%). The NGAL levels in the 12- and 24-h urine samples of these patients were 30 (5-45) and 20 (15-40) ng/ml, respectively, whereas those in patients without CIN were 15 (5-45) and 15 (10-51) ng/ml, respectively (P = 0.8). In patients with CIN, the sensitivity and specificity of NGAL with a cut-off of 22.5 ng/ml were 71.4% and 57.9% in 12-h urine samples, with the negative predictive values (NPV) and positive predictive values (PPV) of 97.1% and 9.4%, respectively. In conclusion, we suggest that urine NGAL with cut-off point of 22.5 ng/ml has acceptable sensitivity and specificity for early diagnosis of CIN in patients with normal serum creatinine, but regarding NPV and PPV the best performance of this value is to rule out the CIN in patients at risk who received contrast media.

Posttransplant diabetes mellitus: incidence and risk factors.

OBJECTIVE: Posttransplant diabetes mellitus (PTDM) is a common and serious complication of renal transplantation. Estimates of the incidence of PTDM after renal transplantation vary between 2% and 54%. The aim of the present study was to evaluate the incidence and risk factors for PTDM among our renal transplant patients. PATIENTS AND METHODS: In this study we evaluated 121 nondiabetic patients with end-stage renal disease (ESRD) who underwent kidney transplantation for the first time at our centers since 2005. All patients received the same protocol of immunosuppressive therapy. PTDM was defined according to the clinical practice recommendations of the American Diabetes Association. RESULTS: At 12 months following renal transplantation, 9.9% of patients developed PTDM. Patients with PTDM were significantly older (P = .013) and had higher body mass index (P = .001). There were significant differences (P

Infertility among female renal transplant recipients.

We studied 122 women with renal allograft transplantation to evaluate their reproductive systems. The patients were recruited from the three main kidney transplant surgery centers in Tehran, from September to October 2005. Fifteen (12%) patients were either in the menopausal stage or had hysterectomies, and the other 33(27%) were unmarried. Of the 76(62%) married women at the reproductive age, 10 (13.1%) had infertility that was defined as the failure of a married woman to conceive after 12 months of frequent intercourse without contraception. Three patients had male factor infertility, three others had ovulatory problems, and four cases were undefined. Only six cases were actively treated by ovulation induction +/- an intrauterine inducer (IUI); two patients became pregnant, while the other four refused infertility treatment. The reasons of unwillingness for infertility treatment included old age (40 years) in one patient, positive HBsAg in one, renal retransplantation in one, and previous clomiphene therapy failure in another. We conclude that the prevalence of infertility among female renal transplant recipients is the same as the general population, and the causes are mostly treatable. However, many are less motivated to be treated for this problem.

Renal allograft accumulation of technetium-99m sulfur colloid as a predictor of graft rejection.

Differentiation between rejection (the most common cause) and many other possibilities for detrimental effects on graft function represents a difficult issue to diagnose the cause of renal allograft dysfunction. This study was designed to determine whether technetium-99m sulfur colloid (TSC) accumulation predicted graft rejection. We prospectively studied 54 episodes of allograft dysfunction in 53 kidney transplant recipients who underwent TSC scintiscanning and graft biopsy. Visual analysis of TSC uptake compared uptake, in the allograft with that in the marrow of the fifth lumbar vertebra (L5). A 3+ result meant that allograft uptake was greater than L5 marrow uptake; 2+, the same; 1+, less and finally 0, no allograft uptake. Transplant accumulation of 2+ or more was considered consistent with rejection (P = .01). Allograft biopsies interpreted based on the Banff Working Classification showed rejection in 45 of 54 renal biopsies with 42 the biopsy-proven rejection episodes showing at least 2+ graft uptake. Furthermore, this nuclear medicine technique had a sensitivity of 93.3%, a specificity of 44.4%, a positive predictive value of 89.3%, a negative value of 57.1% and an efficiency of 83.3% for the diagnosis of renal allograft rejection.

Unwanted pregnancy among kidney transplant recipients in Iran.

To investigate the incidence of unwanted pregnancy among kidney transplant recipients, we studied 86 pregnancies in 64 women with a transplanted kidney. Twenty-five pregnancies were unwanted (29.1%). Pregnancy was terminated by induced abortion in seven patients, and four pregnancies were lost due to spontaneous abortion with one intrauterine fetal death. Only 13 (52%) pregnancies resulted in a live birth. Most of the unwanted pregnancies occurred in women using coitus interruptus (92%) as the only method of contraception. It is concluded that because fertility greatly improves after kidney transplantation, it is necessary to have a family planning counseling session before surgery. If a patient is not interested in future pregnancy, an effective method of contraception should be offered. A woman who has decided against childbearing in the future may decide to have a tubal ligation at the time of transplantation surgery.

Surgical interventions at field hospitals during the Iran and Iraq War (1980-1987).

Surgical treatment of wounded soldiers in the field began in World War II, and the care of the wounded was aided by air, ground, and marine transportation. Even with highly developed facilities, medical care should be started as soon as possible. The Islamic Republic of Iran was under an economic blockade during its war with Iraq. Field hospitals were considered a solution to the problem of transportation shortages. The aim of this study was to assess the surgical interventions of these hospitals. In a descriptive cross-sectional study, data for 7,718 patients admitted to field hospitals (among a total of 173,823 casualties) were analyzed. A checklist was used as the data-collection tool. The data were entered and analyzed by the Statistical Program for the Social Sciences. The type of surgical intervention, duration of the surgery, and frequency of the interventions in each hospital were examined. Laparotomy was the most common and tracheostomy the least common intervention. Shahid Baghaei Field Hospital had the greatest number of admissions. Of all the patients in the Southern Command District who underwent any kind of surgery, 21.53% were operated on in the complex of field hospitals. The surgery time in these hospitals was 156 +/- 69 minutes (mean +/- SD). A great number of the procedures were lifesaving (including laparotomy and chest tube insertion). It seems that these hospitals played a key role in reducing mortality and morbidity during the war.

Therapeutic urogenital modalities during the last three years of the Iran and Iraq War (1985-1987).

OBJECTIVE: Research projects in the field of military medicine have a central role in medical logistical planning. Treatment of traumatic lesions (including urogenital system injuries) is an important aspect of military medicine. Triage for urogenital injuries has specific problems and points of concern. The purpose of this study was to evaluate the role and different types of therapeutic modalities in the treatment of urogenital injuries during the final 3 years of the Iran and Iraq War (1985-1987). METHODS: In a descriptive-analytical study, records of 1,094 patients with urogenital injuries hospitalized from 1985 to 1987 were studied. A checklist and the Statistical Program for the Social Sciences (version 6) were used for data collection and analysis, respectively. A chi 2 test interpreted part of the data. RESULTS: The highest incidence of urogenital injuries and the highest rate of surgical interventions for urogenital injuries were in 1986 and 1987, respectively. The total incidence of urogenital injuries was 0.51%. Among all surgical interventions, bladder repair was most frequent and ureteral repair was least frequent. Partial nephrectomy was the second most frequent surgical intervention and was performed more often than total nephrectomy. There was a significant difference between the urogenital surgery rate and the total surgery rate (chi 2 = 148, p = 0.000). CONCLUSION: The results suggest progress in the triage of patients with urogenital injuries. The lower incidence of urogenital injuries, however, should be interpreted cautiously because it may be attributable to different combat field conditions. Follow-up studies in this group of patients are necessary.

Activation of Mg-ATPase of skeletal-muscle myosin by bovine retinal pigment epithelial actin.

The morphology and function of actin in cultured bovine retinal pigment epithelial (RPE) cells were studied. Filamentous actin was identified with a fluorescent mushroom toxin, nitrobenzoxadiazole (NBD)-phallacidin, specific for actin. Dark-field microscopy of cultured RPE cells revealed numerous pigment granules; fluorescent microscopy identified scattered lipofuscin granules. One-dimensional SDS polyacrylamide gel electrophoresis of urea-soluble proteins extracted from RPE cells showed a 46,000-dalton protein band which comigrated with authentic muscle actin. Densitometric scanning showed that this protein band comprised 7.6% of the total urea-soluble proteins. An actin-activated skeletal-muscle myosin Mg-ATPase assay, using skeletal-muscle heavy meromyosin as enzyme and [gamma-32P]-ATP as substrate, demonstrated functional actin in RPE cell extracts after DEAE-cellulose anion exchange chromatography. The actin-containing protein fractions were eluted at ionic strengths between 0.19 and 0.36 M KCl. The activation of myosin ATPase by actin in RPE cells provides a molecular basis for the phagocytic activity which is important in maintaining the integrity of retinal photoreceptor cells.

Actin in cultured bovine retinal capillary pericytes: morphological and functional correlation.

Actin in cultured bovine retinal capillary pericytes was identified and partially characterized biochemically. The filamentous actin was localized in bovine retinal capillary pericytes using a fluorescent mushroom toxin (nitrobenzoxadiazole-phallacidin) specific for actin. One-dimensional SDS-polyacrylamide-gel electrophoresis of urea-extracted proteins from bovine retinal capillary pericytes revealed a 46,000 MW protein band corresponding to an actin standard, which comprised 7.3% of the total urea-soluble proteins. Actin-activated skeletal muscle myosin Mg2+-ATPase assay, using [gamma-32P]-ATP as substrate, demonstrated functional actin in bovine retinal capillary pericyte extracts after DEAE-cellulose anion-exchange chromatography. The actin-containing protein fractions were eluted at ionic strengths between 0.25 and 0.35 M KCl. The presence of functional actin in pericytes indicated the ability to generate contractile force. This contraction-generating ability may allow pericytes to regulate microvessel caliber and to maintain the integrity of the capillary wall. A lack of this function when pericytes are preferentially lost in diabetic retinal microangiopathy could destabilize the microvessel wall and predispose the capillary to further pathologic changes.

Non-competitive inhibition of myo-inositol transport in cultured bovine retinal capillary pericytes by glucose and reversal by Sorbinil.

myo-Inositol transport by retinal capillary pericytes in culture was characterized. The major myo-inositol transport process was sodium-dependent, ouabain-sensitive, and saturable at 40 mM, indicating a carrier-mediated process. The sodium ion concentration required to produce one-half the maximal rate of myo-inositol uptake ([Na+]0.5) did not show dependence on the external myo-inositol concentration (22.3 mM sodium for 0.005 mM myo-inositol; 18.2 mM sodium for 0.05 mM myo-inositol). myo-Inositol transport was an energy-dependent, active process functioning against a myo-inositol concentration gradient. The kinetics of the sodium-dependent system fitted a 'velocity type' co-transport model where binding of sodium ion to the carrier increased the velocity (Vmax 28 to 313 pmol myo-inositol/micrograms DNA per 20 min when [Na+] varied from 9 to 150 mM) but not the affinity for myo-inositol (Km 0.92 to 0.83 mM when [Na+] varied from 9 to 150 mM). Metabolizable hexoses (D-glucose or D-galactose; greater than 5 mM) inhibited myo-inositol uptake. Dixon-plot analysis indicated that the inhibition was non-competitive with a Ki of 22.7 mM for D-glucose and 72.6 mM for D-galactose. The inhibition was significantly reversed by Sorbinil (0.1 mM), an aldose reductase inhibitor. In contrast, high concentrations of non-metabolizable hexoses (L-glucose, 3-O-methyl-D-glucose), or partially metabolizable 2-deoxy-D-glucose, did not significantly inhibit myo-inositol uptake. The inhibitory effect of D-glucose or D-galactose on myo-inositol transport appeared to be related to glucose or galactose metabolism via the polyol pathway.

Amino acid sequence adjacent to a sulfhydryl group exposed on illumination of bovine rhodopsin.

Two sulfhydryl groups of bovine rhodopsin, available for chemical modification only after bleaching, were specifically labeled with radioactive iodoacetamide. The labeled protein was extensively reduced and alkylated and digested with pronase, and peptides were purified by gel filtration chromatography, anion and cation exchange chromatography, and high pressure liquid chromatography. Purified peptides were detected by their radioactivity, UV spectral properties, and by their fluorescence after reaction with fluorescamine. Sequence analysis of a highly purified peptide established the sequence S-carboxamido[14C]methyl cysteinyl-prolyl-glycine as the site of one of the light-exposed sulfhydryl groups of bovine rhodopsin.