Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles / Avaliação in vivo e in vitro dos efeitos antitumorais de nanopartículas de óxido de ferro e óxido de ferro com núcleo de folato

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis ​​no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles.

Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Long-term clinical outcome following lower limb arterial angioplasty.

INTRODUCTION: The aim of this study was to determine the clinical outcome of lower limb arterial angioplasty in a busy district general hospital practice. PATIENTS AND METHODS: All angioplasties performed from January 1999 to December 2004 were identified and data collected included cardiovascular risk factors, indications for and complications of angioplasty, limb salvage and patient survival rates, and clinically significant re-stenoses. RESULTS: 471 interventions were performed in 385 patients (231 men, 154 women). The median age was 67.9 years (range: 39-93 years). Indications for angioplasty were critical ischaemia (n=247, 52%) and lifestyle-limiting intermittent claudication (n=224, 48%). Stenotic lesions accounted for 378 (80%) cases and occlusion for 93 (20%). Radiological success was obtained in 417 (88.5%), improving to 93.6% if only those in whom access was achieved were included. Post-angioplasty complications were observed in 42/471 (9.1%) of interventions. The actual patient survival at 1, 2, and 3 years was 87.4%, 85.1% and 83.2% respectively. Indication for angioplasty and the number of lesions present were identified as risk factors for outcome on multivariate analysis. The cumulative post-angioplasty patency rates at 1, 2 and 3 years were 86.0%, 83.1% and 81.6% respectively. The only factor associated with patency was the mode of presentation. CONCLUSIONS: Angioplasty for lower limb peripheral vascular disease can be performed safely and efficaciously with a high technical success rate and a low complication rate. The patient survival and post-angioplasty patency data reflect the progressive and multi-site nature of the underlying disease process.

Immunodiagnostic potential of mucin (MUC2) and Thomsen-Friedenreich (TF) antigens in Egyptian patients with colorectal cancer.

OBJECTIVE: Colorectal cancer (CRC) is more common in developed countries and is the third most common cancer among both men and women. CRC provides an attractive model of tumour biology with normal mucosa to adenoma to carcinoma sequence. The TF-antigen (Thomsen-Friedenreich) can be identified by galactose oxidase-Schiff's (GOS) reaction either on tissues or on rectal mucus samples from patients with CRC. TF antigen is expressed in the neoplastic mucosa and not expressed in colonic mucosa of normal subjects. Apomucins play important role in cell signalling and their specific pattern of expression during the different steps of tumor progression toward adenocarcinoma suggests that they play significant roles in tumorigenesis. The family of secreted mucins including MUC2 is contributing in mucus formation to protect underlying epithelia against diverse injuries. The current study was investigated the expression of MUC2 and TF antigens in patients with adenoma and CRC. MATERIALS AND METHODS: MUC2 and TF antigen expressions were detected immunohistochemically in CRC biopsies using specific monoclonal antibodies. Moreover, the TF antigen was invesigated using GOS reaction. RESULTS: The results showed that in normal colonic specimens, MUC2 expression was detected in 20%, while TF antigen was completely negative in 100% of samples as detected by GOS and immunohistochemistry using anti-TF monoclone. Expressions of MUC2, and TF antigen as detected by GOS and anti-TF monoclone were positive in 96%, 80%, and 60% respectively in cases with adenoma. On the other hand, in cases with adenocarcinoma, the expression of MUC2 was seen in 92% of cases, while TF antigen was observed in 84% and 60% of cases as detected by GOS and immunohistochemically respectively. CONCLUSIONS: Thus, it is concluded that the expression of MUC2 and TF antigens are altered during CRC carcinogenesis. Furthermore, MUC2 and TF antigens may have a diagnostic and or prognostic potential in CRC.

Nerve injury in lower limb vascular surgery.

OBJECTIVE: Nerve injury is one of the most common complications of varicose vein surgery and is a frequent cause for litigation but its incidence following lower limb arterial surgery has not been well documented. This study was undertaken to determine the incidence of nerve injury following lower limb arterial surgery. This was addressed in relation to long saphenous or femoral vein harvesting, or re-operative surgery. MATERIALS AND METHODS: A total of one hundred patients who had undergone lower limb arterial reconstruction in the previous five years were invited to participate in this study. Seventy-eight patients responded, of which 44 patients (66 operated legs) agreed to participate. They underwent neurological assessment of the lower limbs. RESULTS: 66.7% of limbs had objective evidence of sensory deficit following lower limb arterial surgery but none had motor deficit. Redo surgery or superficial femoral vein harvest had no influence on the incidence of nerve injury. Below knee incisions had a higher incidence of nerve injury than other approaches. Long saphenous vein harvest significantly increased the rate of nerve injury. CONCLUSIONS: There is a high incidence of sensory nerve damage following lower limb arterial surgery. In the present climate of increasing litigation it is important to know the likely incidence of post-operative nerve damage so that patients can be counselled appropriately during the process of obtaining informed consent.

Paraplegia following elective endovascular repair of abdominal aortic aneurysm: reversal with cerebrospinal fluid drainage.

Paraplegia secondary to spinal cord ischaemia is a rare but devastating complication of abdominal aortic aneurysm repair. We report a case of paraplegia following elective endovascular repair of an infrarenal aortic aneurysm. A cerebrospinal fluid (CSF) drain was immediately inserted and resulted in full neurological recovery. This case highlights the fact that endovascular techniques are prone to similar complications as open surgery, and the importance of prompt cerebrospinal fluid drainage in cases of spinal cord ischaemia.

Value of intraoperative abdominal cavity culture in appendicectomy: a retrospective study.

Appendicectomy is one of the most common surgical emergency procedures. Intraperitoneal culture during appendicectomy is routine practice in some hospitals, while some surgeons advocate abandoning this routine. The aim of our study is to determine the value of intraoperative abdominal cavity culture and its impact on the patient management. Retrospective analysis was performed on 498 patients who underwent appendicectomy over 2.5-year period. The median of the postoperative hospital stay was 2 days, while the median time taken to receive culture results was 3 days. A positive culture was found in 42.6%. Approximately 42.7% of the patients were discharged from the hospital before receiving the culture results. The culture and sensitivity results altered the antibiotic regimen in one patient (0.85%). Intraoperative abdominal cavity culture results were seldom used for clinical management in patients with acute appendicitis. The traditional surgical practice of routinely culturing peritoneal fluid in these patients should be abandoned.

Thoracofemoral bypass using spliced femoral vein with removal of an infected axillobifemoral bypass graft.

A 63-year-old male underwent emergency repair of a ruptured juxtarenal aortic aneurysm via a transabdominal approach using an aorto-bi-iliac Dacron graft. This became infected. A right axillobifemoral bypass was placed and the infected graft was removed with oversewing of the aorta. The patient was re-admitted 8 months later with an infected axillobifemoral prosthesis. We harvested both femoral veins (FV) and spliced them to perform a left thoracobifemoral bypass with simultaneous explantation of the infected graft. The patient remains well with a patent graft 20 months post-operatively.

Massive upper gastrointestinal haemorrhage due to intragastric rupture of a splenic artery aneurysm.

Most cases of splenic artery aneurysm are asymptomatic, being found incidentally at the time of investigations (e.g. ultrasound, computed tomography, angiography) or laparotomy for other conditions. Rupture of a splenic artery aneurysm with erosion into the stomach is a rare cause of massive upper gastrointestinal haemorrhage. This case report is, to our knowledge, only the second case of splenic artery aneurysm presenting with massive upper gastrointestinal haemorrhage due to erosion into the stomach in a nulliparous woman.

Aeromonas hydrophila wound infection in elective surgery.

Patients with diabetes mellitus are subject to wound infection with unusual pathogens. A patient who had colonic surgery developed Aeromonas hydrophila wound infection, which mainly results from contamination by water or soil.

A randomized EPOCH vs. CHOP front-line therapy for aggressive non-Hodgkin's lymphoma patients: long-term results.

BACKGROUND: The value of continuous-infusion chemotherapy (EPOCH) vs. the standard CHOP combination was evaluated in 78 patients with previously untreated aggressive non-Hodgkin's lymphoma in a randomized phase III clinical trial. PATIENTS AND METHODS: The EPOCH regimen given to 38 patients consisted of the drugs etoposide (50 mg/m2), vincristine (0.4 mg/m2), and doxorubicin (10 mg/m2), all given in a continuous infusion on days 1-4. Cyclophosphamide (750 mg/m2) was administered on day 6 as i.v. bolus, while prednisone was given orally 60 mg/m2 on days 1-6. Courses were repeated every three weeks. CHOP was given to 40 patients as routinely prescribed. RESULTS: Forty-eight patients were males and thirty were females. Their ages ranged from 19-75 years (median 45 years). Forty-three (55%) had grade 2 and thirty-five (45%) had grade 3 pathologic subtype. Nine patients (12%) presented with stage I, fourteen (18%) with stage II, forty (51%) with stage III, and fifteen (19%) with stage IV disease. The different clinico-pathologic characteristics, including international index categories, were comparable in the two groups. The number of courses given ranged between 3 and 9 (median 6) for both the EPOCH and CHOP regimens. Complete remission (CR) was achieved in 19 (50%), and 27 (67%) of the 38 and 40 patients for both the EPOCH and CHOP combinations, respectively. After a median observation time of 27 months, the four-year overall and failure-free survival rates were 42% and 30% for the EPOCH and 71% and 54% for the CHOP regimen (P = 0.006 and 0.1 for the overall and FFS rates, respectively). Toxicities were comparable and were mostly of grades 1 and 2, except for hair loss, hematologic toxicities, and infectious episodes which were more common in the EPOCH group. In the EPOCH group, overall survival rates were 55% vs. 22% (P < 0.04) at four years for the low-risk (2 prognostic factors) and high-risk (> 2 factors) groups, respectively. CONCLUSIONS: Thus, it may be concluded that continuous-infusion (EPOCH) chemotherapy did not improve treatment outcome over that of the CHOP regimen for aggressive non-Hodgkin's lymphoma patients.

Radiological manifestations of madura foot in the Eastern Province of Saudi Arabia.

A total of 29 patients with mycologically and histopathologically proven mycetomas were examined for radiological manifestations from April 1984 to March 1996. Twenty cases were actinomycotic mycetomas, while nine were maduromycotic mycetomas. Plain x-rays of the regions of interest were taken in all the cases and CT scan was performed on five selected cases to compare the findings. Soft tissue changes were observed in all the examined cases, while bony changes were observed in 16 (55.7%). CT scan is useful for showing soft tissue changes, erosion and destruction of bone in cases with an early infection only, which cannot be demonstrated in plain radiographs.

A prospective study of lip adaptation during six months of simulated mandibular dental arch expansion.

The stability of dental arch expansion with conventional orthodontic treatments is disappointing. An increase in labial soft tissue pressure resulting from the expansion may contribute to this instability. An 8-month study of lip pressure changes resulting from lip bumper wear has been conducted, but no long-term studies have been conducted on pressure changes resulting from conventional expansion using fixed appliances. The purpose of the current study was to investigate changes in labial soft tissue pressures when conventional expansion was simulated. Twenty-two subjects wore a stent simulating mandibular dental arch expansion. They were instructed to wear the stent full-time. Lip pressure was recorded initially at 1 week, and monthly for 6 months. A repeated measures ANOVA was used for statistical analysis. A statistically significant (P < or = 0.05) increase in pressure was documented after initial insertion of the expansion-simulating stent. The increase was not maintained, suggesting an adaptation of the labial soft tissues.

Lip adaptation to simulated dental arch expansion. Part 1: Reliability and precision of two lip pressure measurement mechanisms.

Understanding the influence of lip and tongue pressure on tooth position requires a reliable method of measuring pressure. A transducer with a beam mechanism has been used extensively in the past. A transducer with a diaphragm mechanism has been recently introduced. Comparative in-vivo tests of these transducers have not been published. The purpose of this study was to investigate transducer reliability and precision. Transducers were placed intraorally in 22 subjects, and two lip pressure measurements were recorded. Paired t-tests and interclass correlations were used to evaluate repeatability and reliability. The error of the method was analyzed for each transducer type. Both transducer types produced measurements that were repeatable and reliable. The error was smaller for the diaphragm transducer. The diaphragm transducer is more precise.

Lip adaptation to simulated dental arch expansion. Part 2: One week of simulated expansion.

An increase in resting lip pressure and the resulting disruption of the intraoral pressure equilibrium may be responsible for the poor stability found with orthodontically expanded dentitions. Passive expansion strategies seek improved stability by altering lip pressure, thus creating a new equilibrium. One of these strategies has been shown to alter pressure favorably. However, pressure changes associated with conventional expansion need to be studied before conclusions regarding the superiority of passive expansion can be drawn. The purpose of this study was to examine lip pressure changes after 1 week of simulated conventional expansion. Twenty-two subjects agreed to wear a mandibular expansion-simulating stent full-time for 1 week. Resting pressure was measured in the midline and right canine areas. Midline lip pressure decreased significantly after 1 week. Resting pressure was measured in the midline and right canine areas. Midline lip pressure decreased significantly after 1 week while pressure in the canine area did not change significantly. This finding suggests an adaptive response that varies according to anatomic location.

Fungal infection as a cause of skin disease in the eastern province of Saudi Arabia: cutaneous candidosis.

In the period between April 1984 and April 1988 a total of 4,294 clinically suspected cases of dermatomycoses were examined for causative fungi. Of these cases 174 (4.1%) were suspected as cutaneous candidosis. These cases belonged to 15 different nationalities. Both sexes were involved (122 males and 52 females). Thirty four cases were prepubertal children while 140 were adults. Of these cases 163 had their clinical diagnosis confirmed by direct microscopy and on culture yielded 164 isolates (Candida albicans 161, C. stellatoidea 1 and Trichophyton rubrum 1).