Obesity-Induced Inflammation Is Associated with Alterations in Subcellular Zinc Pools and Premature Mammary Gland Involution in Lactating Mice.

BACKGROUND: Lactation failure is common in overweight and obese women; however, the precise mechanism remains unknown. OBJECTIVE: We tested the hypothesis that obesity-induced inflammation in the mammary gland (MG) redistributes subcellular zinc pools to promote cell death of mammary epithelial cells (MECs) and premature involution. METHODS: Female DBA/2J mice were fed a high-fat (obese; 45% kcal from fat, n = 60) or control diet (lean; 10% kcal from fat, n = 50) for 5 wk and bred. MG cytokines and macrophage infiltration were determined by reverse transcriptase-polymerase chain reaction and F4/80 staining, respectively. Zinc concentration was analyzed by atomic absorption spectroscopy, and zinc transporters and markers of endoplasmic reticulum (ER) stress, autophagy, and involution were measured by immunoblot. To confirm effects of inflammation, tumor necrosis factor-α (TNF) or vehicle was injected into adjacent MGs of lean lactating C57BL/6 mice (n = 5) and cultured MECs (HC11 cells) were treated with TNF in vitro. RESULTS: Seventy-seven percent of obese mice failed to lactate (lean: 39%; P < 0.001). Obese mice capable of lactating had greater macrophage infiltration (obese: 135 ± 40.4 macrophages/mm(2); lean: 63.8 ± 8.9 macrophages/mm(2); P < 0.001) and elevated TNF expression (P < 0.05), concurrent with lower zrt- irt-like protein 7 abundance (P < 0.05) and higher ER zinc concentration (obese: 0.36 ± 0.004 µg Zn/mg protein; lean: 0.30 ± 0.02 µg Zn/mg protein; P < 0.05) compared with lean mice. Heat shock protein 5 (HSPA5) expression (P < 0.05) was suppressed in the MG of obese mice, which was consistent with HSPA5 suppression in TNF-injected MGs (P < 0.01) and MECs treated with TNF in vitro (P < 0.01). Moreover, obesity increased lysosomal activity (P < 0.05) and autophagy in the MG, which corresponded to increased zinc transporter 2 abundance and lysosomal zinc concentration compared with lean mice (obese: 0.20 ± 0.02 µg Zn/mg protein; lean: 0.14 ± 0.01 µg Zn/mg protein; P < 0.05). Importantly, MGs of obese mice exhibited markers of apoptosis (P = 0.05) and involution (P < 0.01), which were not observed in lean mice. CONCLUSIONS: Diet-induced obesity created a proinflammatory MG microenvironment in mice, which was associated with zinc-mediated ER stress and autophagy and the activation of premature involution.

Mapping the zinc-transporting system in mammary cells: molecular analysis reveals a phenotype-dependent zinc-transporting network during lactation.

The mammary epithelial cell transitions from a non-secreting to a terminally differentiated, secreting cell during lactation. Zinc (Zn) is a key modulator of phenotypic transition as it regulates over 300 biological functions including transcription, translation, energy transformation, intracellular signaling, and apoptosis. In addition, Zn must be redirected from normal cellular functions into the secretory compartment, as many components of the secretory system are Zn-dependent and an extraordinary amount of Zn is secreted (1-3 mg Zn/day) into milk. Herein, we utilized a "systems biology" approach of genomic and proteomic profiling to explore mechanisms through which Zn is reallocated during phenotype transition in the lactating mammary gland from mice and cultured mammary cells. Nine Zn transporters play key roles in Zn redistribution within the network during lactation. Protein abundance of six Zip (Zip3, Zip5, Zip7, Zip8, Zip10, Zip11) and three ZnT (ZnT2, ZnT4, ZnT9) proteins was expanded >2-fold during lactation, which was not necessarily reflected by changes in mRNA expression. Our data suggest that Zip5, Zip8, and Zip10 may be key to Zn acquisition from maternal circulation, while multiple Zip proteins reuptake Zn from milk. Confocal microscopy of cultured mammary cells identified the Golgi apparatus (modulated in part by ZnT5, Zip7, and Zip11) and the late endosomal compartment (modulated in part by ZnT2 and Zip3) as key intracellular compartments through which Zn is reallocated during lactation. These results provide an important framework for understanding the "Zn-transporting network" through which mammary gland Zn pools are redistributed and secreted into milk.

Zinc in specialized secretory tissues: roles in the pancreas, prostate, and mammary gland.

Zinc (Zn) is an essential micronutrient required for over 300 different cellular processes, including DNA and protein synthesis, enzyme activity, and intracellular signaling. Cellular Zn homeostasis necessitates the compartmentalization of Zn into intracellular organelles, which is tightly regulated through the integration of Zn transporting mechanisms. The pancreas, prostate, and mammary gland are secretory tissues that have unusual Zn requirements and thus must tightly regulate Zn metabolism through integrating Zn import, sequestration, and export mechanisms. Recent findings indicate that these tissues utilize Zn for basic cellular processes but also require Zn for unique cellular needs. In addition, abundant Zn is transported into the secretory pathway and a large amount is subsequently secreted in a tightly regulated manner for unique biological processes. Expression of numerous members of the SLC30A (ZnT) and SLC39A (Zip) gene families has been documented in these tissues, yet there is limited understanding of their precise functional role in Zn metabolism or their regulation. Impairments in Zn secretion from the pancreas, prostate, and mammary gland are associated with disorders such as diabetes, infertility, and cancer, respectively. In this review, we will provide a brief summary of the specific role of Zn in each tissue and describe our current knowledge regarding how Zn metabolism is regulated. Finally, in each instance, we will reflect upon how this information shapes our current understanding of the role of Zn in these secretory tissues with respect to human health and disease.

X-ray fluorescence microscopy reveals accumulation and secretion of discrete intracellular zinc pools in the lactating mouse mammary gland.

BACKGROUND: The mammary gland is responsible for the transfer of a tremendous amount of zinc ( approximately 1-3 mg zinc/day) from maternal circulation into milk during lactation to support the growth and development of the offspring. When this process is compromised, severe zinc deficiency compromises neuronal development and immune function and increases infant morbidity and/or mortality. It remains unclear as to how the lactating mammary gland dynamically integrates zinc import from maternal circulation with the enormous amount of zinc that is secreted into milk. METHODOLOGY/PRINCIPAL FINDINGS: Herein we utilized X-ray fluorescence microscopy (XFM) which allowed for the visualization and quantification of the process of zinc transfer through the mammary gland of the lactating mouse. Our data illustrate that a large amount of zinc first accumulates in the mammary gland during lactation. Interestingly, this zinc is not cytosolic, but accumulated in large, discrete sub-cellular compartments. These zinc pools were then redistributed to small intracellular vesicles destined for secretion in a prolactin-responsive manner. Confocal microscopy identified mitochondria and the Golgi apparatus as the sub-cellular compartments which accumulate zinc; however, zinc pools in the Golgi apparatus, but not mitochondria are redistributed to vesicles destined for secretion during lactation. CONCLUSIONS/SIGNIFICANCE: Our data directly implicate the Golgi apparatus in providing a large, mobilizable zinc storage pool to assist in providing for the tremendous amount of zinc that is secreted into milk. Interestingly, our study also provides compelling evidence that mitochondrial zinc pools expand in the mammary gland during lactation which we speculate may play a role in regulating mammary gland function.

High performance plasmonic crystal sensor formed by soft nanoimprint lithography.

This paper describes a new type of plasmonic sensor fabricated by imprint lithography using a soft, elastomeric mold. Angle-dependent, zero-order transmission experiments demonstrate the sensing potential of this device, which uses a two dimensional plasmonic crystal. Full angle-dependent mapping shows that the sensitivity to surface chemical binding events reaches maxima near regions of the plasmonic Brillouin zone where the dispersion curves of multiple surface plasmon polariton modes converge. This behavior, together with the simple, low cost procedures for building the structures, suggests a potentially important role for these devices in high performance chemical and biological sensing.

Manejo quirúrgico de las fracturas del ángulo mandibular / Surgical Management of the fractures of the angle-mandibular

Las fracturas mandibulares representan un reto tanto desde el punto de vista de diagnóstico como manejo terapéutico para el otorrinolaringólogo moderno. El presente estudio presenta la experiencia en el manejo quirúrgico de las fracturas de ángulo mandibular en 56 pacientes adultos evaluados en el Servicio de Otorrinolaringología del Hospital Universitario de Caracas entre agosto de 1998 y agosto de 2003 de estos 54 pacientes pertenecientes al sexo masculino (98 por ciento) y 2 pacientes pertenecientes al sexo femenino (2 por ciento). Las causas mas frecuentes de fractura fueron accidentes automovilísticos (46 por ciento), violencia interpersonal (30 por ciento), accidentes laborales (15 por ciento), caídas (7 por ciento) y otras (2 por ciento). La evaluación clínica de los pacientes demostró que presentaban antecedentes de trauma facial, signos de maloclusión dental, anestesia o parestesia del labio inferior y cambios del contorno facial. A todos los pacientes les fueron practicados estudios radiológicos simples tipo panorámica dental, proyecciones simples de cara y tomografía computada de nariz y senos paranasales. Los pacientes fueron tratados quirúrgicamente a través de reducción quirúrgica temprana abierta a través de un abordaje extraoral con placas de compresión de titanio del Sistema Martin, de 2,0 mm. y con fijación intermaxilomandibular a cuatro puntos o mediante arcos de alambre. La tasa de complicaciones fue de 7 por ciento relacionados con la presencia de infección y seromas de la herida operatoria

Reparación quirúrgica de perforaciones septales a través de la técnica de rinoplastia abierta con rotación de colgajo pediculado miomucoso horizontal labial / Surgical repair of perforations septal through of the technical of rhinoplasty with rotation of surgical flaps pediculado miomucoso horizontal labial

Las perforaciones representan un enigma peculiar para el cirujano reconstructivo nasal y un problema para el paciente. Técnicas como colgajo de mucosa nasal, colgajos cutáneos pediculados, colgajos cutáneos libre, dermis, pericondrio, cartílago, dura craneal y fascia han sido empleados con resultados favorables, sin embargo, una irrigación sanguínea inadecuada llevan frecuentemente a la falla de las técnicas mencionadas anteriormente. Se presenta un estudio prospectivo de un grupo seleccionado de nueve pacientes, cinco de sexo masculino y cuatro de sxo femenino, con edad promedio de 26 años, portadores de perforaciones septales anteriores, sintomáticas, con criterio de reparación quirúrgica, con un promedio de 2 cms, de diámetro, de diversas etiologías, en los cuales se empleó la técnica de rinoplastia abierta como abordaje quirúrgico yla rotación de colgajo pediculado miomucoso del interior de la mucosa del labio superior, con un éxito en el cierre de las mismas de un cien por ciento y una muy baja morbimorbilidad. El abordaje de Rinoplastia abierta acompañado de la rotación de colgajo pediculado miomucoso horizontal labial representa una opción quirúrgica técnicamente sencilla, con una mínima rata de disconfort para el paciente y un éxito elevado en pacientes seleccionados portadores de perforaciones septales anteriores sintomáticas

Manejo quirúrgico de las fracturas mandubulares sinfisiales y parasinfisiales / Managementsurgical of themandibular fractures symphyseal and parasynphyseal

Las fracturas mandibulares se presentan como consecuencias comunes de los traumatismos faciales. El presente estudio presenta la experiencia en el manejo quirúrgico de las fracturas mandibulares sinfisiales y parasinfisiales en 76 pacientes adultos evaluados en el Servicio de Otorrinolaringología del Hospital Universitario de Caracas entre agosto de 1998 y agosto de 2003. De estos, 67 pacientes masculinos (88 por ciento) y 9 femeninos (12 por ciento) las causas mas frecuentes de fractura fueron violencia interpersonal (78 por ciento) y accidentes automovilísticos (20 por ciento). A todos los paciente les fué practicado una evalución otorrinolaringológica completa, de manera complementaria se realizaron estudios radiológicos simples tipo: radiografía panorámica dental y proyecciones simples de macizo facial, se indicó además tomografía computarizada de naríz y senos paranasales y cuello en casos selleccionados. Los pacientes fueron tratados con reducción quirúrgica abierta temprana con placas de compresión de titanio del Sistema Martin de 2,0 mm y con fijación inter-maxilo mandibular a cuatro puntos en casos seleccionados. La tasa de compliciones fue de 8 por ciento relacionados con procesos infecciosos locales en la herida operatoria