Inadequate Bowel Cleansing Efficacy of Split-dose Polyethylene Glycol for Colonoscopy in Type 2 Diabetic Patients: A Prospective and Blinded Study.

BACKGROUND/AIMS: Split-dose polyethylene glycol (PEG) is considered a standard bowel preparation regimen for colonoscopy in the general population. However, it is not clear whether the regimen is optimal for colonoscopy in diabetic patients. The aim of this study was to compare the efficacy and tolerability of split-dose PEG for diabetic versus nondiabetic patients. METHODS: This is a single-center, prospective, investigator-blinded study. A total of 55 consecutive nondiabetic and 50 diabetic patients ingested 2 L PEG solution on the day before the procedure and then 2 L of the solution on the day of colonoscopy. The quality of bowel preparation was graded using the Ottawa scale. RESULTS: There was a significant difference in bowel preparation quality, with a worse preparation except for mid colon in diabetic group (total score: 7.06±1.69 vs. 5.54±1.97, P<0.001; right colon: 2.28±0.57 vs. 1.81±0.72, P<0.001; mid colon: 1.70±0.54 vs. 1.56±0.66, P=0.253; rectosigmoid colon: 1.70±0.76 vs. 1.14±0.62, P<0.001; fluid volume: 1.38±0.53 vs. 1.01±0.59, P=0.001). About 70% of nondiabetic patients had an adequate preparation compared with only 40% of diabetic patients (P=0.003). Diabetic group had longer cecal intubation time (6.4±3.6 vs. 4.5±2.4, P=0.002) and total procedure time (22.1±7.6 vs. 18.1±8.5, P=0.015). Compliance and adverse events were not significantly different. In diabetic group, inadequate bowel preparation had a significant association with higher fasting plasma glucose (136.9±21.8 vs. 121.8±19.4 mg/dL, P=0.016). CONCLUSIONS: Diabetic patients had a worse preparation quality and longer cecal intubation and total procedure time compared with nondiabetic patients. These data suggest that split-dose PEG preparation regimen is not sufficient for optimal bowel preparation in diabetic patients undergoing colonoscopy.

Surface coated Eu(OH)3 nanorods: a facile synthesis, characterization, MR relaxivities and in vitro cytotoxicity.

The water-soluble and biocompatible D-glucuronic acid coated Eu(OH)3 nanorods (average thickness x average length = 9.0 x 118.3 nm) have been prepared in one-pot synthesis. The D-glucuronic acid coated Eu(OH)3 nanorods showed a strong fluorescence at approximately 600 nm with a narrow emission band width. A cytotoxicity test by using DU145 cells showed that D-glucuronic acid coated Eu(OH)3 nanorods are not toxic up to 100 microM, making them a promising candidate for biomedical applications such as fluorescent imaging. The minimum Eu concentration needed for a conventional confocal imaging was estimated to be approximately 0.1 mM. Therefore, D-glucuronic acid coated Eu(OH)3 nanorods can be applied to fluorescent imaging. However, a very tiny magnetization of approximately 1.2 emu/g at room temperature and at an applied field of 5 tesla was observed. As a result, very small r1 and r2 water proton relaxivities were estimated, implying that surface coated Eu(OH)3 nanorods are not sufficient for MRI contrast agents.

Size-classified monitoring of ATP bioluminescence for rapid assessment of biological distribution in airborne particulates.

The COVID-19 pandemic ignited massive research into the rapid detection of bioaerosols. In particular, nanotechnology-based detection strategies are proposed as alternatives because of issues in bioaerosol enrichment and lead time for molecular diagnostics; however, the practical implementation of such techniques is still unclear due to obstacles regarding the large research and development effort and investment for the validation. The use of adenosine triphosphate (ATP) bioluminescence (expressed as relative luminescence unit (RLU) per unit volume of air) of airborne particulate matter (PM) to determine the bacterial population as a representative of the total bioaerosols (viruses, bacteria, and fungi) has been raised frequently because of the high reponse speed, resolution, and compatibility with culture-based bioaerosol monitoring. On the other hand, additional engineering attempts are required to confer significance because of the size-classified (bioluminescence for different PM sizes) and specific (bioluminescence per unit PM mass) biological risks of air for providing proper interventions in the case of airborne transmission. In this study, disc-type impactors to cut-off aerosols larger than 1 µm, 2.5 µm, and 10 µm were designed and constructed to collect PM1, PM2.5, and PM10 on sampling swabs. This engineering enabled reliable size-classified bioluminescence signals using a commercial ATP luminometer after just 5 min of air intake. The simultaneous operations of a six-stage Andersen impactor and optical PM spectrometers were conducted to determine the correlations between the resulting RLU and colony forming unit (CFU; from the Andersen impactor) or PM mass concentration (deriving specific bioluminescence).

Paramagnetic nanoparticle T1 and T2 MRI contrast agents.

There is no doubt that magnetic resonance imaging contrast agents (MRI CAs) can play a vital role in diagnosing diseases. Therefore, demand for new MRI CAs with an enhanced sensitivity and advanced functionalities is very high. Here, paramagnetic nanoparticles (NPs) are reviewed as new potential candidates for either T(1) or T(2) MRI CAs or both. These include surface coated lanthanide (Ln) oxide NPs (Ln = Gd, Dy, and Ho) and manganese oxide NPs. Surface coating materials should be biocompatible and hydrophilic. Compared to conventional large NPs, these surface coated paramagnetic NPs can be made ultrasmall with core particle diameter ranging from 1 to 3 nm, but their magnetic properties are still sufficient for MRI CAs. At this particle diameter, they can be easily excreted from the body through the renal system, which is prerequisite for in vivo applications. Mixed lanthanide oxide NPs into which a fluorescent Ln material is incorporated will be valuable as multiple imaging agents for both MRI-fluorescent imaging (FI) and MRI-cellular imaging (CL). These paramagnetic NPs can be further functionalized towards target-specific imaging, multiplex imaging, and drug delivery.

Ultrasmall Europium, Gadolinium, and Dysprosium Oxide Nanoparticles: Polyol Synthesis, Properties, and Biomedical Imaging Applications.

Imaging agents are crucial in diagnosing diseases. Ultrasmall lanthanide oxide (Ln2O3) nanoparticles (NPs) (Ln = Eu, Gd, and Dy) are promising materials as high-performance imaging agents because of their excellent magnetic, optical, and X-ray attenuation properties which can be applied as magnetic resonance imaging (MRI), fluorescence imaging (FI), and X-ray computed tomography (CT) agents, respectively. Ultrasmall Ln2O3 NPs (Ln = Eu, Gd, and Dy) are reviewed here. The reviewed topics include polyol synthesis, characterization, properties, and biomedical imaging applications of ultrasmall Ln2O3 NPs. Recently published papers were used as bibliographic databases. A polyol method is a simple and efficient one-pot synthesis for preparing ultrasmall Ln2O3 NPs. Ligand-coated ultrasmall Ln2O3 NPs have good colloidal stability, biocompatibility, and renal excretion ability suitable for in vivo imaging applications. Ultrasmall Eu2O3 NPs display photoluminescence in the red region suitable for use as FI agents. Ultrasmall Gd2O3 NPs have r1 values higher than those of commercial molecular contrast agents and r2/r1 ratios close to 1, which make them eligible for use as T1 MRI contrast agents. Ultrasmall Dy2O3 NPs exhibit high r2 and negligible r1 values, which make them suitable for use as T2 MRI contrast agents. All ultrasmall Ln2O3 NPs have high X-ray attenuation powers which make them suitable for use as CT contrast agents. Unmixed, mixed, or doped ultrasmall Ln2O3 NPs with different Ln are extremely useful for in vivo imaging applications in MRI, CT, FI, MRI-CT, MRI-FI, CT-FI, and MRI-CT-FI.

Efficacy and Safety of Pioglitazone versus Glimepiride after Metformin and Alogliptin Combination Therapy: A Randomized, Open-Label, Multicenter, Parallel-Controlled Study.

BACKGROUND: There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM. METHODS: This multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investigator's judgement. RESULTS: Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: -0.81%, P<0.001; glimepiride: -1.05%, P<0.001). However, the pioglitazone-treated group exhibited significantly higher high density lipoprotein cholesterol levels (P<0.001) and significantly lower homeostatic model assessment of insulin resistance values (P<0.001). Relative to pioglitazone, adding glimepiride to metformin plus alogliptin markedly increased the risk of hypoglycemia (pioglitazone: 1/69 cases [1.45%], glimepiride: 14/66 cases [21.21%]; P<0.001). CONCLUSION: Among patients with T2DM inadequately controlled using metformin plus alogliptin, the addition of pioglitazone provided comparable glycemic control and various benefits (improvements in lipid profiles, insulin resistance, and hypoglycemia risk) relative to the addition of glimepiride.

Aqueous extract of the Helianthus annuus seed alleviates asthmatic symptoms in vivo.

Molecular inflammation is a pivotal process in various degenerative immune diseases, including asthma and atopic dermatitis. In this study, we examined the effects of Helianthus annuus seed (HAS) aqueous extract on an in vivo anti-asthmatic model. Ovalbumin-induced mice were orally administered the aqueous extract of Helianthus annuus seeds, and their lungs were assessed by hematoxylin and eosin staining. Moreover, the expression levels of IL-4/IL-13 cytokines and IgE were determined. HAS extract induced a decrease in CD4+ cell number, IL-4/IL-13 expression, and IgE secretion levels in the lungs. Our findings collectively suggest that the HAS extract has considerable potential in reducing the asthma-like symptoms induced by a mouse ovalbumin challenge model. However, further isolation and purification of the extract is required to determine the specific factor(s) responsible for its anti-asthmatic activity.

Anti-tumor activity of Gastrodia elata Blume is closely associated with a GTP-Ras-dependent pathway.

Gastrodia elata Blume (GEB) is an important medicinal plant in Korea. In order to confirm the anti-tumor activities of GEB extracts, we carried out various in vitro anti-tumor assays, including a wound assay and an invasion assay using an ethyl ether extract of GEB. The results showed that the GEB extract exhibits potent anti-tumor activity in vitro in a dose-dependent manner. The expression of CD44, cdc42, Timp-2 or RhoA mRNA did not change by GEB treatment, compared to that of the control. GTP-Ras, an active form of a G-coupled protein family, however, is associated with the anti-tumor activity of GEB extracts. We examined various molecular markers related to metastasis by reverse transcriptase-polymerase chain reaction with the extract of GEB-treated B16 cells. There was an increase in GTP-Ras expression by the Gastrodia elata Blume extract. Together, these results suggest that the Gastrodia elata Blume extract could have potential in alleviating tumorigenesis, by a GTP-Ras-dependent pathway; although the precise molecular mechanisms are still being examined.

Gastrodia elata Blume protects against stress-induced gastric mucosal lesions in mice.

Gastrodia elata Blume (GEB) is a traditional herbal plant that has been used in Asian countries for centuries as an anticonvulsant, analgesic, and also as a sedative for treating general paralysis, epilepsy, vertigo, and tetanus. Although numerous reports have addressed the effects of GEB against degenerative diseases, no previous study has examined the possible gastroprotective effects of GEB. Here, we examined the effects of pretreatment with GEB (0.02 ml/g, p.o.) in a mouse water immersion restraint (WIR) stress-induced gastric lesion model. Our results revealed that mice pretreated with GEB had significantly fewer gastric lesions than their respective controls. Moreover, GEB-treated mice showed significant decreases in serum and gastric nitric oxide (NO) levels to 50 and 28%, respectively. To examine one possible mechanism underlying this effect, we used reverse transcription-polymerase chain reaction (RT-PCR) to examine NOS mRNA expression in gastric lesion tissues. Our results revealed that the mRNA expression of inducible nitric oxide synthase (iNOS) was reduced by approximately 50% in GEB-pretreated mice versus the controls, whereas the mRNA expression levels of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) remained unchanged. These findings collectively suggest that GEB significantly protects the gastric mucosa against WIR-induced gastric damage, at least in part by decreasing NO levels via suppression of iNOS mRNA expression.

Arterial Stiffness Is More Associated with Albuminuria than Decreased Glomerular Filtration Rate in Patients with Type 2 Diabetes Mellitus: The REBOUND Study.

AIM: The aim of this study was to evaluate the association between arterial stiffness and albuminuria and glomerular filtration rate (GFR) in patients with type 2 diabetes mellitus. METHODS: This multicenter cohort study analyzed 2613 patients with type 2 diabetes. Brachial-ankle pulse wave velocity (baPWV) was used as a noninvasive marker of arterial stiffness. Additionally, the patients were categorized into four groups according to their albumin-to-creatinine ratio (ACR, normoalbuminuria versus albuminuria) and estimated GFR (eGFR, <60 mL/min/1.73 m2 versus ≥60 mL/min/1.73 m2). RESULTS: A univariate analysis revealed that maximal baPWV was significantly associated with both the ACR (r = 0.297, P < 0.001) and eGFR (r = -0.220, P < 0.001). A multivariate analysis adjusted for significant clinical variables and eGFR showed that baPWV remained significantly correlated with the ACR (r = 0.150, P < 0.001). Also, baPWV was correlated positively with the ACR in patients with an eGFR ≥ 60 mL/min/1.73 m2 (r = 0.146, P < 0.001). However, baPWV was not correlated with eGFR after adjustment for significant clinical variables. CONCLUSIONS: The present findings indicate that arterial stiffness is more associated with albuminuria than a decrease in GFR in patients with type 2 diabetes mellitus.

Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Gastrointestinal symptoms are common in patients with type 2 diabetes mellitus (T2DM). The prevalence of gastroesophageal reflux disease (GERD) in Korea appears to be increasing. Some studies have shown that T2DM is a risk factor for symptomatic GERD. However, this possibility is still debated, and the pathogenesis of GERD in T2DM is not yet fully understood. The aim of this study was to analyze the prevalence and risk factors (including autonomic neuropathy) of GERD in patients with T2DM. METHODS: This cross-sectional case-control study enrolled T2DM patients (n=258) and healthy controls (n=184). All participants underwent physical examinations and laboratory tests. We evaluated medical records and long-term diabetes complications, including peripheral and autonomic neuropathy in patients with T2DM. Esophagogastroduodenoscopy was performed in all patients. The Los Angeles (LA) classification was used to grade GERD. GERD was defined as LA grade A (or higher) or minimal change with GERD symptoms. GERD symptoms were examined using a frequency scale. Data were expressed as mean±standard error. Independent t-tests or chi-square tests were used to make comparisons between groups. RESULTS: The prevalence of GERD (32.6% vs. 35.9%, P=0.266) and GERD symptoms (58.8% vs. 59.2%, P=0.503) was not significantly different between T2DM patients and controls. We found no significant differences between T2DM patients with GERD and T2DM patients without GERD with respect to diabetic complications, including autonomic neuropathy, peripheral neuropathy, duration of DM, and glucose control. CONCLUSION: The prevalence of GERD in patients with T2DM showed no difference from that of controls. GERD was also not associated with peripheral and cardiovascular autonomic neuropathy, age, or duration of DM in patients with T2DM.

Wisteria floribunda gall extract inhibits cell migration in mouse B16F1 melanoma cells by regulating CD44 expression and GTP-RhoA activity.

Extracts from galls grown on Wisteria floribunda are used as an anti-tumoral preparation in oriental traditional medicine. Here, we investigated the molecular mechanism of this anti-tumoral effect by first examining whether the extract inhibited cell migration in a B16 cell-based wound healing assay. The gall extract delayed wound healing in a dose- and time-dependent manner, indicating that one or more components of the fraction inhibited cell migration. Examination of two molecules known to be involved in metastasis, CD44, and RhoA-GTP, revealed that the gall extract decreased CD44 expression in a concentration-dependent manner, and also increased RhoA-GTP activity in comparison to untreated controls. Taken together, these results suggest that the Wisteria gall extract may inhibit cancer cell migration via inhibition of CD44 mRNA expression and activation of the GTP-RhoA protein.

Current status of prescription in type 2 diabetic patients from general hospitals in busan.

BACKGROUND: Data regarding the prescription status of individuals with diabetes are limited. This study was an analysis of participants from the relationship between cardiovascular disease and brachial-ankle pulse wave velocity in patients with type 2 diabetes (REBOUND) Study, which was a prospective multicenter cohort study recruited from eight general hospitals in Busan, Korea. We performed this study to investigate the current status of prescription in Korean type 2 diabetic patients. METHODS: Type 2 diabetic patients aged 30 years or more were recruited and data were collected for demographics, medical history, medications, blood pressure, and laboratory tests. RESULTS: Three thousands and fifty-eight type 2 diabetic patients were recruited. Mean age, duration of diabetes, and HbA1c were 59 years, 7.6 years, and 7.2%, respectively. Prevalence of hypertension was 66%. Overall, 7.3% of patients were treated with diet and exercise only, 68.2% with oral hypoglycemic agents (OHAs) only, 5.3% with insulin only, and 19.2% with both insulin and OHA. The percentage of patients using antihypertensive, antidyslipidemic, antiplatelet agents was similar as about 60%. The prevalence of statins and aspirin users was 52% and 32%, respectively. CONCLUSION: In our study, two thirds of type 2 diabetic patients were treated with OHA only, and one fifth with insulin plus OHA, and 5% with insulin only. More than half of the patients were using each of antihypertensive, antidyslipidemic, or antiplatelet agents. About a half of the patients were treated with statins and one third were treated with aspirin.

Calix[4]pyrroles bearing proximally meso-meso linking straps: synthesis and anion binding properties.

Calix[4]pyrroles bearing two proximally crossing straps on the same or the opposite sides have been synthesized for the first time. The doubly cis-strapped compound exhibited highly cooperative six-point hydrogen bonding interactions with the anion involving both pyrrolic N-Hs and Ar-Hs.

Cardio-metabolic features of type 2 diabetes subjects discordant in the diagnosis of metabolic syndrome.

BACKGROUND: The aim of this study is to investigate the cardio-metabolic parameters and surrogate markers of insulin resistance in a discordant group of type 2 diabetes (T2DM) subjects who satisfy the Adults Treatment Panel (ATP) III criteria, but not the International Diabetes Federation (IDF) criteria, for metabolic syndrome (MetS). METHODS: We assessed the prevalence of MetS in T2DM subjects (n=167) who were selected from subjects registered at the diabetes center of Dong-A University Medical Center. We used the ATP III criteria and the IDF criteria for the diagnosis of MetS and sorted the subjects into 2 MetS groups: one group diagnosed per ATP III criteria (MetSa) and one diagnosed per IDF criteria (MetSi). We then compared the clinical characteristics, metabolic parameters (homeostasis model assessment of insulin resistance, aspartate aminotransferase, alanine aminotransferase, and uric acid values) and co-morbidities (prevalence of microalbuminuria, fatty liver, and cardiovascular disease) between the MetSa, MetSi, and discordant MetS groups. RESULTS: The prevalence of MetS in the MetSa group (73.6%) was higher than in the MetSi group (62.2%). The MetS prevalence in the discordant group was 11.4%. The discordant group showed no significant differences in clinical characteristics (except waist circumference and body mass index), metabolic parameters, or prevalence of co-morbidities, as compared with subjects with MetS by both criteria. CONCLUSION: In this study, cardio-metabolic features of the subjects diagnosed with MetS using ATP III criteria, but not IDF criteria, are not significantly different from those of subjects diagnosed with MetS using both criteria.

Paramagnetic dysprosium oxide nanoparticles and dysprosium hydroxide nanorods as T2 MRI contrast agents.

We report here paramagnetic dysprosium nanomaterial-based T(2) MRI contrast agents. A large r(2) and a negligible r(1) is an ideal condition for T(2) MR imaging. At this condition, protons are strongly and nearly exclusively induced for T(2) MR imaging. The dysprosium nanomaterials fairly satisfy this because they are found to possess a decent r(2) but a negligible r(1) arising from L + S state 4f-electrons in Dy(III) ion ((6)H(15/2)). Their r(2) will also further increase with increasing applied field because of unsaturated magnetization at room temperature. Therefore, MR imaging and various physical properties of the synthesized d-glucuronic acid coated ultrasmall dysprosium oxide nanoparticles (d(avg) = 3.2 nm) and dysprosium hydroxide nanorods (20 × 300 nm) are investigated. These include hydrodynamic diameters, magnetic properties, MR relaxivities, cytotoxicities, and 3 tesla in vivo T(2) MR images. Here, MR imaging properties of dysprosium hydroxide nanorods have not been reported so far. These two samples show r(2)s of 65.04 and 181.57 s(-1)mM(-1), respectively, with negligible r(1)s at 1.5 tesla and at room temperature, no in vitro cytotoxicity up to 100 µM Dy, and clear negative contrast enhancements in 3 tesla in vivo T(2) MR images of a mouse liver, which will be even more improved at higher MR fields. Therefore, d-glucuronic acid coated ultrasmall dysprosium oxide nanoparticles with renal excretion can be a potential candidate as a sensitive T(2) MRI contrast agent at MR field greater than 3 tesla.

Relationships between Brachial-Ankle Pulse Wave Velocity and Peripheral Neuropathy in Type 2 Diabetes.

BACKGROUND: Brachial-ankle pulse wave velocity (baPWV) is known to be a good surrogate marker of clinical atherosclerosis. Atherosclerosis is a major predictor for developing neuropathy. The goal of this study was to determine the relationship between baPWV and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes. METHODS: A retrospective cross-sectional study was conducted involving 692 patients with type 2 diabetes. The correlation between increased baPWV and DPN, neurological symptoms, and neurological assessment was analyzed. DPN was examined using the total symptom score (TSS), ankle reflexes, the vibration test, and the 10-g monofilament test. DPN was defined as TSS ≥2 and an abnormal neurological assessment. Data were expressed as means±standard deviation for normally distributed data and as median (interquartile range) for non-normally distributed data. Independent t-tests or chi-square tests were used to make comparisons between groups, and a multiple logistic regression test was used to evaluate independent predictors of DPN. The Mantel-Haenszel chi-square test was used to adjust for age. RESULTS: Patients with DPN had higher baPWV and systolic blood pressure, and were more likely to be older and female, when compared to the control group. According to univariate analysis of risk factors for DPN, the odds ratio of the baPWV ≥1,600 cm/sec was 1.611 (95% confidence interval [CI], 1.072 to 2.422; P=0.021) and the odds ratio in female was 1.816 (95% CI, 1.195 to 2.760; P=0.005). CONCLUSION: Increased baPWV was significantly correlated with peripheral neuropathy in patients with type 2 diabetes.

A facile synthesis, in vitro and in vivo MR studies of d-glucuronic acid-coated ultrasmall Ln2O3 (Ln = Eu, Gd, Dy, Ho, and Er) nanoparticles as a new potential MRI contrast agent.

A facile one-pot synthesis of d-glucuronic acid-coated ultrasmall Ln(2)O(3) (Ln = Eu, Gd, Dy, Ho, and Er) nanoparticles is presented. Their water proton relaxivities were studied to address their possibility as a new potential MRI contrast agent. We focused on the d-glucuronic acid-coated ultrasmall Dy(2)O(3) nanoparticle because it showed the highest r(2) relaxivity among studied nanoparticles. Its performance as a T(2) MRI contrast agent was for the first time proved in vivo through its 3 T T(2) MR images of a mouse, showing that it can be further exploited for the rational design of a new T(2) MRI contrast agent at high MR fields.

Water-soluble MnO nanocolloid for a molecular T1 MR imaging: a facile one-pot synthesis, in vivo T1 MR images, and account for relaxivities.

A facile one-pot synthesis of a water-soluble MnO nanocolloid (i.e., D-glucuronic acid-coated MnO nanoparticle) is presented. The MnO nanoparticle in the MnO nanocolloid was coated with a biocompatible and hydrophilic D-glucuronic acid, and its particle diameter was nearly monodisperse and ranged from 2 to 3 nm. The average hydrodynamic diameter of the MnO nanocolloid was estimated to be 5 nm. The MnO nanoparticle was nearly paramagnetic down to T=3 K. The MnO nanocolloid showed a high longitudinal water proton relaxivity of r1=7.02 s(-1) mM(-1) with the r2/r1 ratio of 6.83 due to five unpaired S-state electrons of Mn(II) ion (S=5/2) as well as a high surface to volume ratio of the MnO nanoparticle. High contrast in vivo T1 MR images were obtained for various organs, showing the capability of the MnO nanocolloid as a sensitive T1 MRI contrast agent. The suggested three key-parameters which control the r1 and r2 relaxivities of nanocolloids (i.e., the S value of a metal ion, the spin structure, and the surface to volume ratio of a nanoparticle) successfully accounted for the observed r1 and r2 relaxivities of the MnO nanocolloid.

Paramagnetic ultrasmall gadolinium oxide nanoparticles as advanced T1 MRI contrast agent: account for large longitudinal relaxivity, optimal particle diameter, and in vivo T1 MR images.

Paramagnetic ultrasmall gadolinium oxide (Gd(2)O(3)) nanoparticles with particle diameters (d) of approximately 1 nm were synthesized by using three kinds of Gd(III) ion precursors and by refluxing each of them in tripropylene glycol under an O(2) flow. A large longitudinal relaxivity (r(1)) of water proton of 9.9 s(-1) mM(-1) was estimated. As a result, high contrast in vivo T(1) MR images of the brain tumor of a rat were observed. This large r(1) is discussed in terms of the huge surface to volume ratio (S/V) of the ultrasmall gadolinium oxide nanoparticles coupled with the cooperative induction of surface Gd(III) ions for the longitudinal relaxation of a water proton. It is found from the d dependence of r(1) that the optimal range of d for the maximal r(1), which may be used as an advanced T(1) MRI contrast agent, is 1-2.5 nm.