Acute intake of fructooligosaccharide and partially hydrolyzed guar gum on gastrointestinal transit: A randomized crossover clinical trial.

OBJECTIVES: Dietary fibers, such as fructooligosaccharide (FOS) and partially hydrolyzed guar gum (PHGG) have several gastrointestinal functions. The aims of this study were to evaluate the effect of acute ingestion of FOS and PHGG on the percentage of gastric emptying and small intestinal transit and to evaluate the effect of these dietary fibers on the levels of intestinal hormones-active glucagon-like peptide-1, pancreatic polypeptide, and gastric inhibitory peptide-and their effect on feelings of hunger and satiety and the desire to eat. METHODS: In this crossover, randomized controlled clinical trial, we compared the effects of these two fibers on gastrointestinal transit. The tests were performed using scintigraphy. On three different days, healthy participants consumed a test meal containing 20 g of digestible maltodextrin (placebo), 20 g of FOS, or 20 g of PHGG. RESULTS: The gastric emptying of the FOS-based diet (84.2 ± 9.4%) within 2 h was statistically increased compared with the placebo and PHGG-based diets (78 ± 10.2% and 74 ± 15.3%, respectively; P < 0.05). However, a reduction in small intestinal transit was observed after consumption of both FOS- and PHGG-based diets (28.5 ± 15.56% and 24.2 ± 13.7%, respectively) compared with the placebo diet (41.20 ± 15.4%; P < 0.05). There were no changes in the levels of intestinal hormones, feeling of hunger and satiety, or desire to eat after consuming the three diets (P > 0.05). CONCLUSION: The acute intake of FOS increased gastric emptying, whereas both FOS and PHGG reduced small intestine transit without altering the levels of intestinal hormones, hunger feelings and satiety, or the desire to eat.

The Value of Radionuclide Cisternography in a Case of Spontaneous Cerebrospinal Leak.

Spontaneous intracranial hypotension (SIH) is an infrequent cause of daily persistent orthostatic headache with an incidence of 5 to 100,000 persons/year. In very rare cases, no cause can be found and these conditions may be called spontaneous cerebrospinal fluid leak (CSFL). Radionuclide cisternography (RNC) has played useful role in detecting CSFL. Although RNC has been used in many cases, few have been reported in which CSFL out of the subarachnoid space was detected. A case of CSFL confirmed by RNC direct findings is reported. SIH is difficult to diagnose and 95% of patients may initially receive an incorrect diagnosis. RNC has been shown to be fairly characteristic in SIH patients.

PEGylated versus Non-PEGylated pH-Sensitive Liposomes: New Insights from a Comparative Antitumor Activity Study.

PEGylated liposomes are largely studied as long-circulating drug delivery systems. Nevertheless, the addition of PEG can result in reduced interactions between liposomes and cells, hindering liposomal internalization into target cells. The presence of PEG on the surface of pH-sensitive liposomes is not advantageous in terms of biodistribution and tumor uptake, raising the question of whether the indiscriminate use of PEG benefits the formulation. In this study, two doxorubicin-loaded pH-sensitive liposomal formulations, PEGylated (Lip2000-DOX) or non-PEGylated (Lip-DOX), were prepared and characterized. Overall, the PEGylated and non-PEGylated liposomes showed no differences in size or morphology in Cryo-TEM image analysis. Specifically, DLS analysis showed a mean diameter of 140 nm, PDI lower than 0.2, and zeta potential close to neutrality. Both formulations showed an EP higher than 90%. With respect to drug delivery, Lip-DOX had better cellular uptake than Lip2000-DOX, suggesting that the presence of PEG reduced the amount of intracellular DOX accumulation. The antitumor activities of free-DOX and both liposomal formulations were evaluated in 4T1 breast tumor-bearing BALB/c mice. The results showed that Lip-DOX was more effective in controlling tumor growth than other groups, inhibiting tumor growth by 60.4%. Histological lung analysis confirmed that none of the animals in the Lip-DOX group had metastatic foci. These results support that pH-sensitive liposomes have interesting antitumor properties and may produce important outcomes without PEG.

pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment.

Irinotecan (IRN) is a semisynthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. IRN is used worldwide for the treatment of several types of cancer, including colorectal cancer, however its use can lead to serious adverse effects, as diarrhea and myelosuppression. Liposomes are widely used as drug delivery systems that can improve chemotherapeutic activity and decrease side effects. Liposomes can also be pH-sensitive to release its content preferentially in acidic environments, like tumors, and be surface-functionalized for targeting purposes. Herein, we developed a folate-coated pH-sensitive liposome as a drug delivery system for IRN to reach improved tumor therapy without potential adverse events. Liposomes were prepared containing IRN and characterized for particle size, polydispersity index, zeta potential, concentration, encapsulation, cellular uptake, and release profile. Antitumor activity was investigated in a murine model of colorectal cancer, and its toxicity was evaluated by hematological/biochemical tests and histological analysis of main organs. The results showed vesicles smaller than 200 nm with little dispersion, a surface charge close to neutral, and high encapsulation rate of over 90%. The system demonstrated prolonged and sustained release in pH-dependent manner with high intracellular drug delivery capacity. Importantly, the folate-coated pH-sensitive formulation had significantly better antitumor activity than the pH-dependent system only or the free drug. Tumor tissue of IRN-containing groups presented large areas of necrosis. Furthermore, no evidence of systemic toxicity was found for the groups investigated. Thus, our developed nanodrug IRN delivery system can potentially be an alternative to conventional colorectal cancer treatment.

The role of nuclear medicine in a case of Rendu-Osler-Weber disease with pulmonary involvement.

Rendu-Osler-Weber syndrome or hereditary hemorrhagic telangiectasia (HHT) is a rare systemic disease. Its primary pathogenic expression is multiple arteriovenous malformations (AVM) and severe hypoxia. A case of suspected pulmonary embolism in a 49-year-old male with intestinal, cardiac, and pulmonary HHT affection is reported. Pulmonary AVM could create an apparent mismatch perfusion defect evident upon ventilation and perfusion scan (V/Q scan), leading to misinterpretation. It reinforces the importance between clinics, anatomy, and functional evaluation. Care must be taken when interpreting V/Q scan and the reporting physician must be alert to the possible sources of errors.

Influence of PEG coating on the biodistribution and tumor accumulation of pH-sensitive liposomes.

Liposomes are lipid vesicles widely used as nanocarriers in targeted drug delivery systems for therapeutic and/or diagnostic purposes. A strategy to prolong the blood circulation time of the liposomes includes the addition of a hydrophilic polymer polyethylene glycol (PEG) moiety onto the surface of the vesicle. Several studies claim that liposome PEGylation by a single chain length or a combination of PEG with different chain lengths may alter the liposomes' pharmacokinetic properties. Therefore, the purpose of this study was to evaluate the influence of PEG on the biodistribution of pH-sensitive liposomes in a tumor-bearing animal model. Three liposomal formulations (PEGylated or not) were prepared and validated to have a similar mean diameter, monodisperse distribution, and neutral zeta potential. The pharmacokinetic properties of each liposome were evaluated in healthy animals, while the biodistribution and scintigraphic images were evaluated in tumor-bearing mice. High tumor-to-muscle ratios were not statistically different between the PEGylated and non-PEGylated liposomes. While PEGylation is a well-established strategy for increasing the blood circulation of nanostructures, in our study, the use of polymer coating did not result in a better in vivo profile. Further studies must be carried out to confirm the feasibility of the non-PEGylated pH-sensitive liposomes for tumor treatment.