Innovative multiple nanoemulsion (W/O/W) based on Chilean honeybee pollen improves their permeability, antioxidant and antibacterial activity.

Beehive derivatives, including honeybee pollen (HBP), have been extensively studied for their beneficial health properties and potential therapeutic use. Its high polyphenol content gives it excellent antioxidant and antibacterial properties. Today its use is limited due to poor organoleptic properties, low solubility, stability, and permeability under physiological conditions. A novel edible multiple W/O/W nanoemulsion (BP-MNE) to encapsulate the HBP extract was designed and optimized to overcome these limitations. The new BP-MNE has a small size (∼100 nm), a zeta potential greater than +30 mV, and efficiently encapsulated phenolic compounds (∼82%). BP-MNE stability was measured under simulated physiological conditions and storage conditions (4 months); in both cases, stability was promoted. The formulation's antioxidant and antibacterial (Streptococcus pyogenes) activity was analyzed, obtaining a higher effect than the non-encapsulated compounds in both cases. In vitro permeability was tested, observing a high permeability of the phenolic compounds when they are nanoencapsulated. With these results, we propose our BP-MNE as an innovative solution to encapsulate complex matrices, such as HBP extract, as a platform to develop functional foods.

Equatorial wrinkles in the human lens capsule.

Equatorial wrinkles, or crenations, have been previously observed around the equator in coronal images of the human ocular lens. However, wrinkles are typically not apparent when the lens is viewed from saggital directions. In the current paper, the existence and geometry of these wrinkles is shown to be consistent with a mechanical model of the isolated lens, in which the capsule is held in a state of residual tension by a spatially uniform internal pressure. The occurrence of equatorial wrinkles is therefore seen to be a mechanical consequence of the spheroidal shape of the lens capsule and an excess intralenticular pressure. New observations are made, on post mortem lenses, on the geometric arrangement of these equatorial wrinkles. These observations indicate a well-defined pattern in which wrinkles exists along meridional lines in the equatorial regions of the lens. A preliminary 'puncture test' is used to demonstrate that the residual stresses within the capsule in the equatorial region of the lens are broadly consistent with the proposed mechanical model of the lens capsule. It is suggested that the presence of equatorial wrinkles may have an influence on the mechanical performance of the capsule during the accommodation process.

Transanal TATA/TME: a case-matched study of taTME versus laparoscopic TME surgery for rectal cancer.

BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) has always made more sense in the colorectal field where the target organ for entry houses the pathology. To address the question whether an adequate total mesorectal excision (TME) for rectal cancer can be performed from a transanal bottoms-up approach, we performed a case-matched study. METHODS: Starting in 2009, transanal TME (taTME) surgery was selectively used for rectal cancer after neoadjuvant therapy and prospectively entered into a database. Between March 2012 and February 2014, 17 consecutive taTME rectal cancer patients were identified and case-matched to multiport laparoscopic TME (MP TME) based on age, body mass index, uT stage, radiation dose, level in the rectum, and procedure. Perioperative outcomes, morbidity, mortality, local recurrence, completeness of TME, and radial and distal margins were analyzed. Statistically significant differences were identified using Student's t test. RESULTS: There were 12 transanal abdominal transanal (TATA)/5 abdominoperineal resection procedures in each group. Data regarding overall/taTME/MP TME are as follows: % positive-circumferential margin: 2.9/0/5.9 % (p = 0.32). Distal margin: 0/0/0 %. Complete or near-complete TME: 97.1/100/94.1 % (p = 0.32). Incomplete TME 2.9/0/5.9 % (p = 0.32). Local recurrence: 2.9/5.9/0 % (p = 0.32). There were no perioperative mortalities. Morbidity in each group: 26.4/23.5/29.4 % (p = 0.79). There were no differences in perioperative or postoperative outcomes except days to clear liquids (1/2 days, p = 0.03) and largest incision length (1.3/2.6 cm, p = 0.05). CONCLUSIONS: We demonstrated no differences in perioperative/postoperative outcomes or pathologic TME outcomes of transanal or bottoms-up TME compared to standard laparoscopic TME. TaTME is a promising progressive approach to NOTES and deserves additional evaluation.

Prevalence, sociodemographic distribution, treatment and control of diabetes mellitus in Panama.

BACKGROUND: To estimate the prevalence, socio-demographic distribution, treatment and control of diabetes mellitus in Panama. METHODS: A cross-sectional, descriptive study was conducted in the provinces of Panama and Colon, applying a survey on cardiovascular risk factors and analyzing biochemical indicators in 3590 persons. A single-stage, probabilistic, and randomized sampling strategy with a multivariate stratification was used. Individuals with a previous medical diagnosis of diabetes, glycemia ≥ 126 mg/dl and/or glycosylated hemoglobin ≥ 6.5% (≥ 48 mmol/mol) were considered with diabetes mellitus. The prevalence estimates were calculated as percentages with 95% confidence intervals and a p value. Logistic regression was used to identify the sociodemographic variables that were significantly associated with diabetes. Odds ratio and p values were calculated using 2 x 2 tables, and a value of p ≤ 0.05 was considered statistically significant. RESULTS: Of the participants, 7.3% (262/3590) were aware of having diabetes and 2.2% (78/3590) were unaware. The estimated prevalence of diabetes mellitus was 9.5% (340/3590) and increased in proportion to increasing age. The logistic regression revealed relationships between diabetes and age, sex, area of residence and sociocultural groups. 77.9% of the people aware of having diabetes received treatment and 53.4% have not stabilized the disease. CONCLUSIONS: The research evidenced a high prevalence of diabetes mellitus in Panama, where being Afro-Panamanian and 50 years of age or older are sociodemographic risk factors for DM. Due to the complications that the disease may present we recommend actively searching for such cases to increase diagnosis of people unaware of having diabetes.

Mutation screening of spastin, atlastin, and REEP1 in hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) comprises a group of clinically and genetically heterogeneous diseases that affect the upper motor neurons and their axonal projections. Over 40 chromosomal loci have been identified for autosomal dominant, recessive, and X-linked HSP. Mutations in the genes atlastin, spastin and REEP1 are estimated to account for up to 50% of autosomal-dominant HSP and currently guide the molecular diagnosis of HSP. Here, we report the mutation screening results of 120 HSP patients from North America for spastin, atlastin, and REEP1, with the latter one partially reported previously. We identified mutations in 36.7% of all tested HSP patients and describe 20 novel changes in spastin and atlastin. Our results add to a growing number of HSP disease-associated variants and confirm the high prevalence of atlastin, spastin, and REEP1 mutations in the HSP patient population.

Immunotherapy as an adjuvant therapy in the management of advanced, surgically resected, melanoma.

Metastatic melanoma continues to be one of the most devastating of all cancers. It is a heterogeneous solid tumor whose treatment is challenging and difficult. It afflicts thousands of otherwise healthy patients annually, and clinicians have yet to discover an effective treatment for locally advanced disease. Over the years, much attention has been devoted to the development of an effective adjuvant treatment for patients with resected melanoma who remain at high risk for recurrence. The new advances in the understanding of melanoma's microenvironment and the complexity of its disease process, makes it clear that the treatment approach to this disease needs to be multi-directional. Numerous studies have tested various immunotherapeutic strategies in the treatment of advanced melanoma, in particular. These strategies include melanoma vaccines, interferon-alpha, interleukin-2 (IL-2), and dendritic cell vaccines. The Dr. Wallack's Surgery Research Laboratory has been studying melanoma vaccines for the past three decades. The first generation melanoma vaccine proposed by the Laboratory showed promising results in a subset of patients. Recently, the same Laboratory has produced a second generation melanoma vaccine (DC-Melvac) that consists of five human melanoma cell lines, a recombinant vaccinia virus that encodes for IL-2, as well as dendritic cells that have been programmed to recognize certain melanoma associated antigens. DC-MelVac was recently approved by the Food and Drug Administration for its use in Phase I clinical trials. These trials are expected to be underway in the near future. The ensuing review discusses many of the immunotherapeutic strategies that have been studied in the treatment of melanoma, including DC-MelVac.

Certificación del origen botánico de miel y polen corbicular pertenecientes a la comuna de Litueche, IV Región de Chile / Certification of the botanical origin of honey and corbicular pollen belonging to the commune of Litueche, IV Region of Chile

The objective of this study was to certify and register the botanical origin of honey and corbicular pollen from beehives located at the community of Litueche. For this purpose, a survey of vegetation was conducted within a radio of 2 km from the beehives. The results show that from a total of 120 species found, 59 were native, and the most representative families are Asteraceae, Rosaceae and Papilionaceae. Most of the species present some medicinal uses, and are actually used or have a potential use. In general, they do not present conservation problems. In order to analyze the honey samples, the quantification of pollen grains and the Analysis of Proportions allowed us to determine their frequency and their relative importance. All the study samples presented less than 50% of pollen grains of single species, so they were classified as multifloral honeys. Species that appeared with significant importance are Retanilla trinervis, Lotus uliginosus, Rubus ulmifolius and Quillaja saponaria. The corbicular pollen samples were different in the different beehives analyzed. The results show that not all the species flowering at the same time in the area, were selected by the honeybees as nectar and pollen sources.

New arylpiperazine derivatives with high affinity for alpha1A, D2 and 5-HT2A receptors.

A series of novel long-chain arylpiperazines bearing a coumarin fragment was synthesized and the compounds were evaluated for their affinity at alpha(1), D(2 )and 5-HT(2A) receptors. Most of the new compounds showed high affinity for the three types of receptors alpha(1A), D(2) and 5-HT(2A) which depends, fundamentally, on the substitution of the N(4) of the piperazine ring. From the series emerged compound 6, which had an haloperidol-like profile at D(2) and 5HT(2A) receptors (pK(i) values of 7.93 and 6.76 respectively). The higher alpha(1A) receptor affinity (pA(2)=9.07) of this compound could contribute to a more atypical antipsychotic profile than the haloperidol.

Iridoids from Stachys grandidentata (Labiatae).

Monomelittoside, melittoside, 8-acetyl-harpagide, harpagide, ajugol, 5-desoxy-harpagide, 5-desoxy-8-acetylharpagide and catalpol were isolated from the aerial parts of S. grandidentata.

Inhibition of Mycobacterium tuberculosis growth by saringosterol from Lessonia nigrescens.

Assay-guided fractionation of an antitubercular extract obtained from Lessonia nigrescens yielded the phytosterol saringosterol as its active component. No appreciable toxicity against Vero cells was observed for this compound. Saringosterol was also synthesized by oxidation of fucosterol. The MIC values for antitubercular activity of saringosterol and its 24S and 24R epimers were determined as 0.25, 1, and 0.125 microg/mL.

Propolis from Chilean matorral hives.

Viscidone (0.5%), vanillin, 3',4'-(methylendioxy)acetophenone, 3-ethoxy-4-methoxybenzaldehyde, cinnamic acid, 3-methoxy-4-hydroxymethyl ester were isolated from propolis of hives from Cuncumen. This is the first report on propolis composition of an arid and a Mediterranean type climate area.

Phenolic compounds of propolis from Central Chilean matorral.

Pinocembrin, acacetin, galanguin, izalpin, kaempferide, prenyletin and diarytheptane were isolated from propolis from Central Chile.

Conformationally constrained butyrophenones with affinity for dopamine (D(1), D(2), D(4)) and serotonin (5-HT(2A), 5-HT(2B), 5-HT(2C)) receptors: synthesis of aminomethylbenzo[b]furanones and their evaluation as antipsychotics.

A series of novel conformationally restricted butyrophenones (6-aminomethyl-4,5,6,7-tetrahydrobenzo[b]furan-4-ones bearing 4-(6-fluorobenzisoxazolyl)piperidine, 4-(p-fluorobenzoyl)piperidine, 4-(o-methoxyphenyl)piperazine, 4-(2-pyridyl)piperazine, 4-(2-pyrimidinyl)piperazine, or linear butyro(or valero)phenone fragments) were prepared and evaluated as antipsychotic agents by in vitro assays for affinity for dopamine receptors (D(1), D(2), D(4)) and serotonin receptors (5-HT(2A), 5-HT(2B), 5-HT(2C)), by neurochemical studies, and by in vivo assays for antipsychotic potential and the risk of inducing extrapyramidal side effects. Potency and selectivity depended mainly on the amine fragment connected to the cyclohexanone structure. Compounds 20b, with a benzoylpiperidine moiety, and 20c, with a benzisoxazolyl fragment, were selective for 5-HT(2A) receptors. The in vitro and in vivo pharmacological profiles of N-[(4-oxo-4,5,6, 7-tetrahydrobenzo[b]furan-6-yl)methyl]-4-(p-fluorobenzoyl)piperidine (20b, QF1003B) and N-[(4-oxo-4,5,6, 7-tetrahydrobenzo[b]furan-6-yl)methyl]-4-(6-fluorobenzisoxazol-3-yl)p iperidine (20c, QF1004B) suggest that they may be effective as antipsychotic (neuroleptic) drugs.

Synthesis and biological studies of glycosyl dopamine derivatives as potential antiparkinsonian agents.

A new approach to deliver dopamine into the central nervous system, based on the use of D-glucose as transportable agent, has been studied. Glycosyl dopamine derivatives bearing the sugar moiety linked to either the amino group or the catechol ring of dopamine through amide, ester or glycosidic bonds were synthesised as potential antiparkinsonian agents. Studies on the binding to dopamine D2 receptor, in vitro stability, and locomotive effect in mice of the synthetic glycoconjugates are reported.

Binding and preliminary evaluation of 5-hydroxy- and 10-hydroxy-2,3, 12,12a-tetrahydro-1H-[1]benzoxepino[2,3,4-ij]isoquinolines as dopamine receptor ligands.

The N-methyl, N-ethyl, and N-n-propyl derivatives of 5-hydoxy- and 10-hydroxy-2,3,12,12a-tetrahydro-1H-[1]benzoxepino[2,3, 4-ij]isoquinolines were prepared as monophenolic ligands for the dopamine receptor and evaluated for their affinity at D(1)-like and D(2)-like subtypes. All compounds showed very low D(1) affinities. This could be ascribed to the absence of a catechol nucleus or of the beta-phenyldopamine pharmacophore. Only the N-methyl-5-hydroxy- (5a), N-methyl-10-hydroxy- (6a), and N-methyl-4-bromo-10-methoxy-2,3, 12,12a-tetrahydro-1H-[1]benzoxepino[2,3,4-ij]isoquinolines (26a) bound the D(2) receptors with low affinity, in the same range as dopamine. In compounds 5a and 6a, the 2-(3-hydroxyphenyl)ethylamine moiety does not meet the requirements of the D(2) agonist pharmacophore: namely, the 2-(3-hydroxyphenyl)ethylamine does not reach the trans, fully extended conformation. The three compounds did not interact with recombinant human D(4) receptors, and only 5a showed low affinity for rat recombinant D(3) receptors. Analysis of the influence of Na(+) on [(3)H]spiperone binding showed that 5a displays a potential dopamine D(2) agonist profile, whereas 6a probably has a dopamine D(2) antagonist activity. The D(2) agonist activity of 5a was proved by the effects on prolactin release from primary cultures of rat anterior pituitary cells.

Two novel flavanones from Greigia sphacelata.

As part of our continuing phytochemical investigations of plants from arid environments in Chile, the aerial parts of Greigia sphacelata were examined. Two novel flavanones, 5,7,3'-trihydroxy-6, 4',5'-trimethoxyflavanone (1) and 5,3'-dihydroxy-6,7,4', 5'-tetramethoxyflavanone (2), as well as eight known compounds-1, 3-O-di-trans-p-coumaroylglycerol (3), 1-O-trans-p-coumaroylglycerol (4), a mixture of 1-(omega-feruloyldocosanoyl)glycerol (5) and 1-(omega-feruloyltetracosanoyl)glycerol (6), trans-ferulic acid 22-hydroxydocosanoic acid ester (7), arborinone (8), arborinol (9), and isoarborinol (10)-were isolated.

Antibacterial diterpenoid acids from Azorella compacta.

The two novel diterpenoid acids mulin-12,14-dien-11-on-20-oic acid (1) and mulin-12-ene-11,14-dion-20-oic acid (2) have been isolated from Azorella compacta. Their structures have been elucidated by 1D and 2D NMR methods. In contrast to the closely related known mulinolic acid (3) and its dehydration product (4) these new natural products have been shown to exhibit antimicrobial activity.

Phytochemical, morphological, and biological investigations of propolis from Central Chile.

Propolis from central Chile was investigated for its plant origin by microscopical analysis of pollen grains and leaf fragments found in the sample. The pollen grains that appear with significant higher frequency in the sample corresponded to four native and two introduced species, whereas leaf fragments corresponded to four native species. Seventeen phenolic compounds that belong to the phenylpropane, benzaldehyde, dihydrobenzofuran, or benzopyran classes, were isolated from an organic extract that was found to have a moderate growth inhibitory activity against Mycobacterium avium, M. tuberculosis, and two strains of Staphylococcus aureus. The components responsible for activity were determined.

Diterpenoids from Baccharis pingraea.

From the aerial parts of Baccharis pingraea the known furolabdane, angeloyl-gutierrezianolic acid (1); two novel diterpenoids, furolabda-6,8-dien-17-oic acid (2) and furolabd-7-en-17-oic acid (3); and the known linear diterpenoid, (10E)-centipedic acid (4), were isolated. LC/MS suggested the presence of gutierrezianolic acid (5). The structures of the new compounds were elucidated by 1D and 2D NMR methods.