Near‐Infrared Fluorescent Silica/Porphyrin Hybrid Nanorings for In Vivo Cancer Imaging

Ring‐shaped silica nanoparticles are synthesized with a high tetrakis(4‐carboxyphenyl)porphyrin (TCPP) content or silica/TCPP hybrid nanorings (HNRs) using a one‐pot sol‐gel reaction with a TCPP‐binding silica precursor for fluorescence imaging of tumor. The shape of the HNRs is a reflection of abundant ring‐shaped TCPP aggregates in the silica matrix. The HNRs are of a size that makes them susceptible to the enhanced permeability and retention effect. For comparison, the TCPP‐doped silica nanoparticles are synthesized using a conventional method. The nanoparticles are spherical in shape because little TCPP is contained in the silica matrix and are designated as TCPP‐containing silica nanospheres (NSs). The absorption bands of the HNRs shift by about 20 nm toward longer wavelengths compared with the TCPP bands. This redshift leads the excitation wavelength of the HNRs into the near‐infrared (NIR) region. Therefore, the HNRs are excited by NIR light to emit strong fluorescence, although the NSs emit no fluorescence. The PEGylated HNRs (PEG‐HNRs) are uncharged and possess a significantly longer blood circulation time than PEG‐NSs. The PEG‐HNRs accumulate in tumor through multiple factors including their size, uncharged surface, unique shape, and long circulation time in blood, resulting in the acquisition of clear images of tumor.     

The Role of Leaky Gut in Nonalcoholic Fatty Liver Disease: A Novel Therapeutic Target

The liver directly accepts blood from the gut and is, therefore, exposed to intestinal bacteria. Recent studies have demonstrated a relationship between gut bacteria and nonalcoholic fatty liver disease (NAFLD). Approximately 10–20% of NAFLD patients develop nonalcoholic steatohepatitis (NASH), and endotoxins produced by Gram-negative bacilli may be involved in NAFLD pathogenesis. NAFLD hyperendotoxicemia has intestinal and hepatic factors. The intestinal factors include impaired intestinal barrier function (leaky gut syndrome) and dysbiosis due to increased abundance of ethanol-producing bacteria, which can change endogenous alcohol concentrations. The hepatic factors include hyperleptinemia, which is associated with an excessive response to endotoxins, leading to intrahepatic inflammation and fibrosis. Clinically, the relationship between gut bacteria and NAFLD has been targeted in some randomized controlled trials of probiotics and other agents, but the results have been inconsistent. A recent randomized, placebo-controlled study explored the utility of lubiprostone, a treatment for constipation, in restoring intestinal barrier function and improving the outcomes of NAFLD patients, marking a new phase in the development of novel therapies targeting the intestinal barrier. This review summarizes recent data from studies in animal models and randomized clinical trials on the role of the gut–liver axis in NAFLD pathogenesis and progression.     

Stress concentrations in a plate with two unequal circular holes

This paper contains an exact solution for stresses which are produced in an infinite plate with two unequal circular holes by a uniform tension, an internal pressure or uniform shearing forces along a hole. Bipolar coordinates are used in the solution. Expressions of the hoop stress at the edges of holes are explicitly derived and the stress concentration factors are calculated. The stresses in an infinite plate with two contacted unequal circular holes are also discussed.     

Lysosomal enzyme beta-glucuronidase. Release from regenerating liver after partial hepatectomy

In 12 dogs, 70% hepatectomy was performed to investigate the changes in serum lysosomal enzyme beta-glucuronidase activities, and to compare them with other liver functions and with the restoration of liver mass. Three dogs died within 24 hours without recovering consciousness from anesthesia, and one died on the fourth postoperative day because of hepatic insufficiency. The other eight dogs were killed at various postoperative times up to eight weeks. Regeneration of the remaining liver occurred rapidly after operation. The peak elevation of serum glutamic oxaloacetic transaminase activity was found on the first postoperative day, with a steady return to normal within two or three weeks. To the contrary, the serum activity of beta-glucuronidase decreased during the first three days, but increased substantially between the seventh and 14th postoperative day, when regeneration was considered to be maximum. The results seem to indicate that serial determinations of lysosomal enzyme activities in the blood can be a beneficial biochemical index for detection of progressing liver regeneration following partial hepatectomy.     

Preparation of b-Axis-Oriented MFI Zeolite Thin Films Using Slow Dissolution of Source Material

A novel in situ hydrothermal method involving the slow dissolution of silicate glasses as a source material was used to successfully prepare b -axis-oriented high-silica zeolite ZSM-5 (MFI) thin films.     

Biliary and fecal steroid excretion in rats fed partially hydrogenated soybean oil

Male Wistar rats were fed cholesterol-free or cholesterol-enriched diets containing partially hydrogenated soybean oil with different levels of trans-fatty acids or unhydrogenated soybean oil at the 10% level. The linoleic acid content of hydrogenated fat diets was adjusted to 3.6% of the total energy. Hydrogenated fat diets contained 29% and 41% trans-acids, mainly as t-18:1. Trans-fats exerted no untoward effects on growth parameters, but increased liver weight. Dietary hydrogenated fats influenced neither the concentration nor composition of biliary steroids, irrespective of the presence or absence of cholesterol in the diet. In rats fed a cholesterol-free diet, daily fecal output of neutral and acidic steroids was enhanced by hydrogenated fats and the magnitude of augmentation was proportional to the dietary level of trans-fatty acids. The increased fecal steroid excretion corresponded to an increase in total excreta. Hydrogenated fats also tended to enhance bile acid excretion when feeding a cholesterol-enriched diet. The results suggest that dietary trans-fatty acids, in relation to cis-polyunsaturated fatty acids, provoke demonstrable change in steroid homeodynamics.     

A case of progressive multifocal leukoencephalopathy with methionine uptake demonstrated by PET]

We report here a 55-year-old man with progressive multifocal leukoencephalopathy (PML) associated with chronic adult T cell leukemia (ATL). Neurological examination revealed mild dementia, right homonymous hemianopsia and visual agnosia. Serologically anti-HTLV-I antibody was positive. Peripheral blood analysis showed ATL cells up to 23% in white blood cells. Because he did not have symptoms or signs directly related to ATL, it was considered that he had chronic ATL. T2-weighted cranial MRI demonstrated multiple hyperintensity lesions confined to the white matter from the bilateral occipital to parietal lobes, without enhancement after gadolinium administration or mass effect. We performed stereotactic biopsy of the left occipitoparietal white matter. Histological examination of the biopsied specimens showed demyelinated lesions, containing foamy macrophages and bizarre astrocytes. Oligodendrocytes contained nuclear inclusions which reacted with an antibody against the JC virus (JCV) antigen. These findings were consistent with those of PML. The genomic analysis of JCV from the biopsied brain revealed deletions in the regulatory region. We investigated cerebral blood flow, glucose and amino acid metabolism in this patient using positron emission tomography, and obtained the following three characteristic findings in the lesions: 1) luxury perfusion state, 2) decreased fluorodeoxyglucose (FDG) uptake, and 3) increased methionine (Met) uptake. These findings resembled those of low grade tumors.