Fourier transform infrared absorption (FTIR) on dry stratum corneum, corneocyte-lipid interfaces: experimental and vibrational spectroscopy calculations.

Many questions concerning the biophysical and physiological properties of skin are still open. Skin aging, permeability, dermal absorption, hydration, and drug transdermal delivery, are few examples of processes with unveiled underlying mechanisms. In this work, it is presented a comparison between Fourier transform infrared absorption (FTIR) of dry stratum corneum and stratum corneum under lipase action supported by first-principles density functional vibrational calculations. The molecular structure of stratum corneum was modeled by an archetype of its hygroscopic proteic portion inside the corneocytes, the natural moisturizing factor, coupled to glycerol molecules which represent the lipid fraction of stratum corneum. Vibrational spectra were calculated and compared to experimental data obtained on the animal model of stratum corneum. The experimental results indicated prominent spectral differences between dry and lipase-treated stratum corneum. Principal components analysis and hyerarchical clustering indicated that 1200, 1650, and 1695 cm-1 bands are the most influential on the discrimination. It is noticed that bands in the fingerprint region (800-1800 cm-1) were correctly assigned. Moreover, the calculations revealed the existence of two coupled vibration between the hydroxyl group of lipid and methylene (1120 and 1160 cm-1), which are of special interest since they probe the lipid-amino acid coupling. The model was also able to predict the shear modulus of dry stratum corneum in excellent agreement with the reported values from the literature. Other physical/chemical properties could be calculated exploring the chemical accuracy and molecular resolution of this model. Research in dermatology, cosmetology, and biomedical engineering in the specific topics of drug delivery and/or mechanical properties of skin are examples of fields that would potentially take advantage of this approach.

Analysis of particles from hamster lungs following pulmonary talc exposures: implications for pathogenicity.

BACKGROUND: Talc, a hydrous magnesium silicate, often used for genital hygiene purposes, is associated with ovarian carcinoma in case-control studies. Its potential to cause inflammation, injury, and functional changes in cells has been described. A complication of such studies is that talc preparations may be contaminated with other materials. A previous study by (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) used a hamster model to study talc and granite dust exposure effects on various biochemical and cellular inflammatory markers. Our current study accessed key materials used in that 1987 study; we re-analyzed the original talc dust with contemporary scanning electron microscopy and energy dispersive x-ray analysis (SEM/EDX) for contaminants. We also examined the original bronchoalveolar lavage (BAL) cells with polarized light microscopy to quantify cell-associated birefringent particles to gain insight into the talc used. RESULTS: SEM/EDX analyses showed that asbestos fibers, quartz, and toxic metal particulates were below the limits of detection in the original talc powder. However, fibers with aspect ratios ≥3:1 accounted for 22% of instilled material, mostly as fibrous talc. Talc (based on Mg/Si atomic weight % ratio) was the most abundant chemical signature, and magnesium silicates with various other elements made up the remainder. BAL cell counts confirmed the presence of acute inflammation, which followed intratracheal instillation. Measurements of cell associated birefringent particles phagocytosis revealed significant differences among talc, granite, and control exposures with high initial uptake of talc compared to granite, but over the 14-day experiment, talc phagocytosis by lavaged cells was significantly less than that of granite. Phagocytosis of talc fibers by macrophages was observed, and birefringent particles were found in macrophages, neutrophils, and multinucleate giant cells in lavaged cells from talc-exposed animals. CONCLUSION: Our data support the contention that talc, even without asbestos and other known toxic contaminants, may elicit inflammation and contribute to lung disease. Our findings support the conclusions of (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) study. By analyzing particulate exposures with polarized light microscopy and SEM/EDX, fibrous talc was identified and a distinctive pattern of impaired particulate ingestion was demonstrated.

Dissociation of the AhR/ARNT complex by TGF-ß/Smad signaling represses CYP1A1 gene expression and inhibits benze[a]pyrene-mediated cytotoxicity.

Cytochrome P450 1A1 (CYP1A1) catalyzes the metabolic activation of polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (B[a]P) and is transcriptionally regulated by the aryl hydrocarbon receptor (AhR)/AhR nuclear translocator (ARNT) complex upon exposure to PAHs. Accordingly, inhibition of CYP1A1 expression reduces production of carcinogens from PAHs. Although transcription of the CYP1A1 gene is known to be repressed by transforming growth factor-ß (TGF-ß), how TGF-ß signaling is involved in the suppression of CYP1A1 gene expression has yet to be clarified. In this study, using mammalian cell lines, along with shRNA-mediated gene silencing, CRISPR/Cas9-based genome editing, and reporter gene and quantitative RT-PCR assays, we found that TGF-ß signaling dissociates the B[a]P-mediated AhR/ARNT heteromeric complex. Among the examined Smads, Smad family member 3 (Smad3) strongly interacted with both AhR and ARNT via its MH2 domain. Moreover, hypoxia-inducible factor 1α (HIF-1α), which is stabilized upon TGF-ß stimulation, also inhibited AhR/ARNT complex formation in the presence of B[a]P. Thus, TGF-ß signaling negatively regulated the transcription of the CYP1A1 gene in at least two different ways. Of note, TGF-ß abrogated DNA damage in B[a]P-exposed cells. We therefore conclude that TGF-ß may protect cells against carcinogenesis because it inhibits CYP1A1-mediated metabolic activation of PAHs as part of its anti-tumorigenic activities.

Propylene Glycol Caprylate as a Novel Potential Absorption Enhancer for Improving the Intestinal Absorption of Insulin: Efficacy, Safety, and Absorption-Enhancing Mechanisms.

Sodium caprate (C10) acts as an absorption enhancer. However, the absorption-enhancing effects of compounds with structures similar to C10 have not been characterized. In the present study, insulin was used as a model drug. We examined the effects of C10 and its related compounds on intestinal absorption of insulin using an in situ closed loop in rats. Insulin absorption was significantly enhanced by propylene glycol caprylate (Sefsol-218), a C10-related compound, after large intestinal administration. In addition, activity of lactate dehydrogenase did not increase in the intestinal epithelium in the presence of Sefsol-218 at concentrations equivalent to or lower than 1% (v/v). However, a significant increase in lactate dehydrogenase activity was observed in response to C10. These findings suggested that Sefsol-218 was safer than C10. Furthermore, mechanistic studies showed that increased membrane fluidity and loosening of tight junctions (TJs) might be underlying mechanisms by which this compound improved intestinal absorption of insulin. Furthermore, Sefsol-218 opened TJs by reducing the expression of claudin-4, which is a major TJ protein. These findings suggested that Sefsol-218 effectively enhanced intestinal insulin absorption without causing serious damage to the intestinal epithelium.

Deep Inferior Epigastric Artery Perforator Flap Breast Reconstruction in Patients With Previous Bariatric Surgery: Is It Safe and Feasible?

BACKGROUND: Obesity is widely recognized as a major health concern and a leading cause of preventable death. The correlation between obesity and breast cancer has been thoroughly described by several authors. Bariatric surgery is often associated with redundant abdominal tissue, often leading patients to consider body-contouring procedures. Autologous tissue breast reconstruction using the deep inferior epigastric artery perforator (DIEP) flap has advantages because it is tissue that is normally discarded during postbariatric body contouring. METHODS: We conducted a retrospective chart review of 18 DIEP flaps performed by the senior author in 9 patients for breast reconstruction between February 2008 and May 2013. All patients underwent mastectomies. All patients underwent bariatric surgery preceding breast reconstruction. Breast reconstruction was performed immediately in 13 cases and delayed in 5 cases. RESULTS: Mean age of the study population was 44.6 years (range, 41-57 years). The mean maximum body mass index of the patients was 44 (range, 37.6-52.1), and the mean current body mass index at the time of the reconstruction was 30.7 (range, 24.3-38.1). No intraoperative complications were reported. No fascia or muscle was taken during flap dissection. Mean operative time was 632 minutes (range, from 480 to 750 minutes). Average hospital stay was 4 days. No partial or total flap loss was reported. There were no postoperative hernias or bulges at the abdominal donor site. CONCLUSIONS: This series represents the largest group of patients undergoing DIEP flap breast reconstruction after bariatric surgery. In the hands of experienced microsurgeons, breast reconstruction with the DIEP flap in postbariatric patients represents a low-risk option with high satisfaction.

The Nipple-Areola Preserving Mastectomy: A Multistage Procedure Aiming to Improve Reconstructive Outcomes following Mastectomy.

UNLABELLED: Ischemia of the nipple-areola complex (NAC) and periareolar tissue is commonly seen following tissue-preserving mastectomies for small invasive and noninvasive cancers. The nipple-areola preserving mastectomy is a multistage procedure in which the NAC and central mastectomy flap tissue is surgically delayed to improve the survivability in patients undergoing mastectomies followed by reconstruction. METHODS: We conducted a retrospective chart review of 20 patients undergoing the 2-stage nipple-areola preserving mastectomy: the first stage comprised undermining the NAC and raising the breast skin flaps, with placement of a silicone sheet in the dissected pocket. The second stage followed 2-3 weeks after the NAC delay, with patients undergoing nipple-sparing mastectomies. RESULTS: Mean age was 46.2 years (range, 23-59 years). Indications included breast cancer in 18 patients and BRCA gene mutation prophylaxis in 2 patients. None were actively smoking. Mean time between delay of flaps and breast reconstructions was 16 days (range, 10-35 days). One patient underwent bilateral nipple resection at the time of mastectomies due to a subareolar nipple biopsy positive for ductal carcinoma in situ. One patient underwent left nipple excision after a skin nipple biopsy was positive for metaplasia. No signs of NAC vascular compromise were observed in any of the cases. CONCLUSIONS: Our 2-stage approach benefits patients undergoing nipple-sparing mastectomy, especially those at high-risk, by safely increasing survivability of the native breast skin envelope and NAC, while improving oncologic outcomes by identification of subareolar malignancies and sentinel node status before mastectomy and reconstruction.

Delayed Mammoplasty with Silicone Gel Implants following DIEP Flap Breast Reconstruction.

UNLABELLED: The deep inferior epigastric artery perforator (DIEP) flap is a state-of-the-art option for breast reconstruction. However, thin patients with medium- to large-size native breasts are not ideal candidates due to the limited amount of available tissue. We reviewed our experience utilizing the DIEP flap in combination with prosthetic implants. METHODS: We conducted a retrospective chart review of 7 patients, totaling 11 implants, who underwent breast reconstruction with the DIEP flap and subsequent mammoplasty. All cases underwent previous mastectomies. No implant placement was offered at the time of their DIEP flap reconstruction. Immediate breast reconstruction with the DIEP flap was performed in 9 cases, whereas 2 required delayed reconstruction secondary to postmastectomy radiotherapy. No patients received postreconstruction radiotherapy. Breast asymmetry and inadequate volume were the primary indications for mammoplasty. For all cases, we used smooth, round silicone gel implants, which were placed in the subpectoral region. RESULTS: Mean age was 43 years. One patient was actively smoking. Four patients underwent bilateral implant placement. The mean time of delay between breast reconstruction and mammoplasty was 61 weeks. Average volume of silicone implants was 229 mL. A medial pedicle vertical mastopexy was performed in 1 patient on a nonreconstructed breast to achieve symmetry. Five patients underwent nipple reconstruction. All patients underwent delayed mammoplasty without intraoperative complications and good aesthetic results. CONCLUSIONS: Delayed mammoplasty following DIEP flap breast reconstruction is a safe and feasible procedure for patients who seek an aesthetic and natural-looking breast but lack adequate abdominal tissue.

Molecular model for hydrated biological tissues.

A density-functional microscopic model for soft tissues (STmod) is presented. The model was based on a prototype molecular structure from experimentally resolved type I collagen peptide residues and water clusters treated in periodic boundary conditions. We obtained the optimized geometry, binding and coupling energies, dipole moments, and vibrational frequencies. The results concerning the stability of the confined water clusters, the water-water, and water-collagen interactions were successfully correlated to some important experimental trends of normal and inflammatory tissues.

Laparoscopic resection of colon cancer and synchronous liver metastasis.

The recommended surgical approach to synchronous colorectal metastasis has not been clarified. Simultaneous open liver and colon resection for synchronous colorectal carcinoma has been shown beneficial when compared to staged resections. A review of the literature has shown the benefits of both laparoscopic colon resection for colorectal cancer and laparoscopic left lateral segmentectomy in liver disease. We present the case of a 60-year-old male with sigmoid colon carcinoma and a synchronous solitary liver metastasis localized to the left lateral segment. Using laparoscopic techniques, we were able to achieve simultaneous resection of the sigmoid colon and left lateral liver segment.