A blackberry-dill extract combination synergistically increases skin elasticity.

BACKGROUND: The loss of structural elastin due to intrinsic and extrinsic ageing results in the skin's inability to stretch and recoil (decrease in elasticity) and manifests as loss of skin firmness and sagging. While other extracellular matrix (ECM) components such as collagen and hyaluronic acid are continually synthesized and assembled through life, elastic fibres are not. Elastic fibre assembly and functionality require fibre cross-linking, induced by the lysyl oxidase-like (LOXL) enzymes, which sharply decrease during ageing. OBJECTIVE: To evaluate the enhanced elastogenic effect of a blackberry-dill extract combination, which was hypothesized to induce elastin fibre component synthesis, fibre cross-linking and reduce elastin fibre degradation. METHODS: The blackberry and the dill extracts were tested separately and in combination to confirm single ingredient bioactivity and synergistic benefits. Human skin explants, dermal fibroblasts, elastase assays, ELISAs, quantitative real-time PCRs and spectrofluorometer measurements were used. Moreover, a double-blinded, placebo-controlled clinical study was carried out to assess skin elasticity using Cutometer and histologically from biopsies. RESULTS: The blackberry extract induced elastin gene expression, elastin promoter activity and inhibited elastic fibre degradation by matrix metalloproteinases (MMPs) 9 and 12. The dill extract induced elastin, collagen and LOXL1 gene expression, resulting in enhanced fibre cross-linking in human skin explants. Clinically, the blackberry and dill combination treatment displayed synergistic pro-elasticity activity as compared to each ingredient alone and placebo. CONCLUSION: Taken together, these results demonstrated the two multimodal plant-based extracts complemented each other in terms of bioactivity and resulted in a synergistic elastogenesis induction.

CONTEXTE: la perte de l'élastine structurelle causée par un vieillissement intrinsèque et extrinsèque provoque l'incapacité de la peau à s'étirer et à rebondir (diminution de l'élasticité) et se manifeste comme une perte de fermeté et un relâchement de la peau. Alors que d'autres composants de la matrice extracellulaire (MEC), tels que le collagène et l'acide hyaluronique sont continuellement synthétisés et assemblés tout au long de la vie, les fibres élastiques ne le sont pas. L'assemblage et la fonctionnalité des fibres élastiques nécessitent une réticulation des fibres, causée par les enzymes de type lysyle oxydase (LOXL), qui diminuent fortement au cours du vieillissement. OBJECTIF: évaluer l'effet élastogène amélioré d'une combinaison d'extrait de mûre et d'aneth, qui était supposée induire la synthèse des composants des fibres d'élastine, la réticulation des fibres et réduire la dégradation des fibres d'élastine. MÉTHODES: les extraits de mûre et d'aneth ont été testés séparément et ensemble pour confirmer la bioactivité d'un seul ingrédient et les avantages synergiques. Des explants de peau humaine, des fibroblastes cutanés, des dosages d'élastase, des ELISA, des analyses PCR quantitatives en temps réel et des mesures de spectrofluorimètre ont été utilisés. De plus, une étude clinique en double aveugle, contrôlée par placebo, a été réalisée pour évaluer l'élasticité de la peau à l'aide du cutomètre et histologiquement à partir de biopsies. RÉSULTATS: l'extrait de mûre a induit l'expression génique de l'élastine, l'activité de promoteur de l'élastine et a inhibé la dégradation des fibres élastiques par des métalloprotéinases matricielles (MPM) 9 et 12.L'extrait d'aneth a causé l'expression génique de l'élastine, du collagène et du gène LOXL1, entraînant une amélioration de la réticulation des fibres dans les explants de peau humaine. Cliniquement, le traitement par une combinaison de mûre et d'aneth a montré une activité de pro-élasticité synergique par rapport à chaque ingrédient seul et au placebo. CONCLUSION: ensemble, ces résultats ont démontré que les deux extraits de plantes multimodales se complètent en termes de bioactivité et ont entraîné une induction synergique de l'élastogenèse.

Effects of low-fat milk consumption on metabolic and atherogenic biomarkers in Korean adults with the metabolic syndrome: a randomised controlled trial.

BACKGROUND: Previous studies of the health effects of low-fat milk or dairy consumption on the metabolic syndrome have yielded inconsistent results. The present study aimed to investigate the effects of low-fat milk consumption on traits associated with the metabolic syndrome, as well as inflammatory and atherogenic biomarkers, in Korean adults with the metabolic syndrome. METHODS: Overweight Koreans with the metabolic syndrome (n = 58) were recruited and randomly assigned to either the low-fat milk or control group. The low-fat milk group was instructed to consume two packs of low-fat milk per day (200 mL twice daily) for 6 weeks, and the control group was instructed to maintain their habitual diet. Clinical investigations were conducted during the screening visit, on study day 0, and after 6 weeks. RESULTS: No significant differences in changes in body mass index, blood pressure, lipid profile and adiponectin levels, as well as levels of inflammatory markers, oxidative stress markers and atherogenic markers, were found between the low-fat milk and control groups. However, compared to the controls, significant favourable decreases in serum soluble vascular adhesion molecule-1 and endothelin-1 levels were found in the 12 subjects with high blood pressure and in the 18 subjects with hypertriglyceridaemia in the low-fat milk group. CONCLUSIONS: The present study did not demonstrate an overall beneficial effect of low-fat milk consumption in subjects with the metabolic syndrome. However, low-fat milk consumption may have a favourable effect on atherogenic markers in subjects with high blood pressure or hypertriglyceridaemia.

In-vitro study on ureteral smooth muscle contractility with tamsulosin, nifedipine, and terpene mixture (Rowatinex®).

AIM: The aim of this study was to evaluate whether tamsulosin, an alpha-blocker, has an effect on decreasing spontaneous ureteral contractility with or without phenylephrine, an alpha-agonist. Additionally, nifedipine and a terpene mixture (Rowatinex®) were tested and compared with each other. METHODS: We obtained ureteral segments from freshly killed eight-week-old rabbits. Preparation was performed in an aerated Krebs buffer (95% oxygen and 5% carbon dioxide) at a constant temperature of 37 °C. All segments were suspended into organ tissue baths containing aerated Krebs buffer using stainless steel hangers and clips. The ureter was divided into four segments: upper, middle, low and uretero-vesical junction. Each ureteral segment was suspended longitudinally and circularly by opposite corners, respectively. Tamsulosin, nifedipine, and the terpene mixture were separately applied into the segments. Contractile activities of each drug were recorded and analyzed by the PowerLab data acquisition system (AD instruments CO., USA). The area under the curve was compared between before and after each drug application for each 5 minutes with or without pheylephrine. Statistical analysis was performed using the unpaired Student's t test. RESULTS: Under Krebs solution, ureteral smooth muscle contractility was significantly decreased in all segments over 10(-6) M in tamsulosin, 10(-7) M in nifedipine and 0.001x1 concentrations in the terpene mixture (P=0.038). However, under Krebs solution with 10(-5) M phenylephrine, there was no significant difference at all concentrations in tamsoluin and nifedipine. In contrast to tamsolusin and nifedipine, there was a significant decrease in ureteral smooth muscle contractility in most of segments at 0.01x1 concentrations (P=0.042) in the terpene mixture. CONCLUSION: Tamsulosin, nifedipine, and the terpene mixture showed the effect on spontaneous ureteral contractility. In particular, the terpene mixture might have the better effect on decreasing ureteral smooth muscle contractility.

Expression of mucins and trefoil factor family protein-1 in the colon of pigs naturally infected with Salmonella typhimurium.

The expression patterns of different mucins (MUC1, MUC2, MUC4, MUC5AC, MUC5C and MUC6) and trefoil factor family protein-1 (TFF1) in the colon of healthy pigs and pigs naturally infected with Salmonella typhimurium is reported. Twenty infected pigs approximately 80-160 days of age from 20 different herds were studied. These animals had similar microscopical change in colonic tissue characterized by mucosal erosion or sloughing and acute inflammation. S. typhimurium was cultured from all lesions and the identity of each isolate was confirmed by serotyping. Immunohistochemical studies of colonic tissue revealed reduced expression of MUC4 on the surface of the cryptal epithelium of S. typhimurium-infected pigs compared with non-infected pigs (P<0.001). By contrast, colon from infected animals had increased expression of MUC5AC (P<0.0001) and TFF1 (P=0.0095) relative to controls and there was a significant positive correlation between expression of these two molecules (Spearman coefficient 0.64, P<0.0001). Further studies are needed to evaluate the functional relationship between altered expression of these molecules and inflammation in Salmonella-infected pigs.

Enzymatic hydrolysis of heated whey: iron-binding ability of peptides and antigenic protein fractions.

This study evaluated the influence of various enzymes on the hydrolysis of whey protein concentrate (WPC) to reduce its antigenic fractions and to quantify the peptides having iron-binding ability in its hydrolysates. Heated (for 10 min at 100 degrees C) WPC (2% protein solution) was incubated with 2% each of Alcalase, Flavourzyme, papain, and trypsin for 30, 60, 90, 120, 150, 180, and 240 min at 50 degrees C. The highest hydrolysis of WPC was observed after 240 min of incubation with Alcalase (12.4%), followed by Flavourzyme (12.0%), trypsin (10.4%), and papain (8.53%). The nonprotein nitrogen contents of WPC hydrolysate followed the hydrolytic pattern of whey. The major antigenic fractions (beta-lactoglobulin) in WPC were degraded within 60 min of its incubation with Alcalase, Flavourzyme, or papain. Chromatograms of enzymatic hydrolysates of heated WPC also indicated complete degradation of beta-lactoglobulin, alpha-lactalbumin, and BSA. The highest iron solubility was noticed in hydrolysates derived with Alcalase (95%), followed by those produced with trypsin (90%), papain (87%), and Flavourzyme (81%). Eluted fraction 1 (F-1) and fraction 2 (F-2) were the respective peaks for the 0.25 and 0.5 M NaCl chromatographic step gradient for analysis of hydrolysates. Iron-binding ability was noticeably higher in F-1 than in F-2 of all hydrolysates of WPC. The highest iron contents in F-1 were observed in WPC hydrolysates derived with Alcalase (0.2 mg/kg), followed by hydrolysates derived with Flavourzyme (0.14 mg/kg), trypsin (0.14 mg/kg), and papain (0.08 mg/kg). Iron concentrations in the F-2 fraction of all enzymatic hydrolysates of WPC were low and ranged from 0.03 to 0.05 mg/kg. Fraction 1 may describe a new class of iron chelates based on the reaction of FeSO4 x 7 H2O with a mixture of peptides obtained by the enzymatic hydrolysis of WPC. The chromatogram of Alcalase F-1 indicated numerous small peaks of shorter wavelengths, which probably indicated a variety of new peptides with greater ability to bind with iron. Alcalase F-1 had higher Ala (18.38%), Lys (17.97%), and Phe (16.58%) concentrations, whereas the presence of Pro, Gly, and Tyr was not detected. Alcalase was more effective than other enzymes at producing a hydrolysate for the separation of iron-binding peptides derived from WPC.

Status analysis and strategic framework for sanitation management in Asia and Africa.

Following rapid population increase and industrial development, the ever increasing environmental pollution and the associated sanitation-related problem are no longer regional or local but have become an issue requiring global-dimensional concern and the provision of problem-solving alternatives. Especially, since most problems result from inappropriate sewerage and the lack of sewage treatment system are in a serious state occurring in economically underdeveloped regions, and as such, their significance is enormous. The United Nations Environment Programme (UNEP) has been making efforts to establish the technology selection methodology applicable in developing countries, through the accurate status, investigation and analysis of the wastewater management state in Asian and African regions, and the sanitation management guideline utilisable by political leaders or decision-makers. As part of this effort, the Korea Institute of Water Environment (KIWE), together with the UNEP, selected China and Vietnam (in Asia) and Kenya and Ethiopia (in Africa) as subject countries to investigate and perform on-site sanitation management investigations and analysis in this research. Results obtained from the on-site investigation were analysed, and in order to be helpful in establishing a strategy for sanitation management in underdeveloped countries, the strategic framework (SF) has been made based on characterised results.

Long-term results of single-stage reduction surgery for the treatment of macrodactyly.

We report the long-term results of a single-stage reduction procedure for the treatment of macrodactyly. Six patients (eight cases) were included. These patients underwent a single-stage operation that included debulking with resection of the hypertrophied digital nerve and distal interphalangeal joint fusion or corrective osteotomy. Plain radiographs and functional parameters were assessed. Aesthetic improvement was achieved in all patients. The mean ratios of the lengths and circumference differences between the affected digit and the corresponding normal digit on the other hand were 1:1 and 1:1, respectively. The mean range of motion in the proximal interphalangeal joint was 76°. A sensory deficit in the lateral pulp of the distal phalangeal area was observed in three fingers. The Disabilities of the Arm, Shoulder and Hand score ranged from 0 to 9 (mean 4). The long-term results of the single-stage reduction procedure were satisfactory, as demonstrated by the excellent adjustment of the length and acceptable circumference of the affected digits. LEVEL OF EVIDENCE: IV.

Endoscopic Treatment for Persistent Hematospermia: A Novel Technique Using a Holmium Laser.

PURPOSE: We present our endoscopic technique for treating ejaculatory duct and seminal vesicle diseases with a holmium laser. MATERIALS AND METHODS: Fifteen patients with persistent hematospermia were enrolled in this study from June 2007 to April 2014. All patients had failed medical treatments. All patients were evaluated with transrectal ultrasound and pelvic computed tomography or magnetic resonance imaging. We performed endoscopic treatment with a semi-rigid ureteroscope after dilation using a guidewire and ureteral serial dilator. A holmium laser was used to incise the obstructed ejaculatory duct, coagulate hemorrhagic mucosa, and fragment stones in the ejaculatory duct or seminal vesicles. Stones were removed using a basket and forceps. RESULTS: The mean duration of hematospermia was 30.6 months. Mean patient age was 45.3 years. The mean serum levels of prostate-specific antigen and testosterone were 1.36 and 4.95 ng/mL, respectively. No operative complications were encountered. Mean operative time was 35.4 min. Seven patients had ejaculatory duct or seminal vesicle stones, which were subsequently determined to be carbonate apatite, mucin, struvite, and calcium oxalate dehydrate stones. Mean duration of follow-up was 32.1 months. Although two patients showed recurrent hematospermia 11 and 12 months after the operation, hematospermia resolved in 13 patients (86.7%). The infertile patient showed an improved semen finding and had a successful pregnancy. CONCLUSION: Endoscopic treatment using a holmium laser is minimally invasive and was effective for treating ejaculatory duct and seminal vesicle diseases, which are the main cause of hematospermia.

The anticancer effect of chaetocin is enhanced by inhibition of autophagy.

Chaetocin is a fungal metabolite that possesses a potent antiproliferative activity in solid tumors by inducing cell death. Although recent studies have extended the role of chaetocin in tumors, the underlying molecular mechanisms such as the downstream cascade that induces cell death has not clearly been elucidated. In this study, we show that chaetocin is able to induce both apoptosis and autophagy in several hepatoma cell lines including HepG2, Hep3B and Huh7 cell lines. Moreover, we found that the inhibition of caspase-3/7 activity by z-VAD-fmk treatment was able to block chaetocin-mediated cell death, whereas blocking autophagy by Bafilomycin A1 or the knockdown of autophagy protein 5 enhanced cell death mediated by chaetocin. These findings suggest that chaetocin has a potent anticancer effect against hepatoma. Inhibition of autophagy may potentiate anticancer effects of chaetocin thus providing evidence that combined treatment with chaetocin and autophagy inhibitors will be an effective strategy for treating cancer.

Somatostatin-secreting islet cell tumor (somatostatinoma): suppression of growth hormone (GH) release induced by GH-releasing hormone.

A patient with a somatostatin (SRIH)-secreting islet cell tumor, whose only symptoms were dyspepsia and anemia, is described. The diagnosis of somatostatinoma was based on high plasma SRIH concentrations and immunocytochemical findings. The pancreatic exocrine response to secretin was decreased, whereas the insulin and/or glucagon responses to glucose and arginine were normal. Although the basal plasma GH concentration was normal, the plasma GH response to GHRH was subnormal. Gel permeation chromatography studies indicated that SRIH-14 was the predominant form of SRIH in plasma as well as in tumor tissue.

Minimal deviation melanoma with epidermotropic metastases arising in a congenital nevus.

A congenital nevus removed from a 20-year-old woman was found to contain a minimum deviation melanoma. Subsequently, there were multiple nodular recurrences in the region of the excision as well as in the grafted skin. Microscopically the recurrent lesions closely resembled the original nevus, including the junctional activity and even the grafted skin. Lymph node metastasis occurred 5 1/2 years after excision of the nevus. This is the first report of a minimal deviation melanoma arising in a congenital nevus with epidermotropic metastases.

Metastasizing atrial myxoma.

Tumors that were identical in morphology to a previously excised atrial myxoma were found in the choroid plexus and the scapula of a 46-year-old woman 8 and 10.5 years, respectively, after cardiac surgery. Ultrastructurally the scapular lesion resembled previously reported atrial myxomas. This case demonstrates that atrial myxoma is a true neoplasm capable of metastatic spread despite its slow growth and innocuous histologic appearance.

Composite pleomorphic xanthoastrocytoma and ganglioglioma: report of four cases and review of the literature.

Composite pleomorphic xanthoastrocytoma (PXA)-ganglioglioma (GG) is a rare recently described entity. Only three examples have been documented, one of which showed evidence of malignant transformation. We report an additional four cases and update the literature. With the exception of an 82-year-old man, all patients have been under 30 years of age. The temporal lobe was involved in three cases and cerebellum in another three. Radiologic features were those common to PXA and GG. Histologically, all were "collision tumors" composed of abutting, although spatially distinct, PXA and GG components. In two cases, the second element was only recognized at reexcision or recurrence. Histologic anaplasia, always in the PXA component, was evident as brisk mitotic activity and/or necrosis in five cases. Of the seven patients, one died of disease 17 years after the onset of seizures and after multiple recurrences, the last of which largely resembled glioblastoma. We conclude that the composite PXA-GG is a rare neoplasm that shares many features of its individual components. In addition to its temporal lobe predilection, the cerebellum is frequently affected. As when it occurs in isolation, the PXA component of composite PXA-GG possesses the potential for malignant transformation.

Myelodysplastic syndrome: diagnostic implications of cytochemical and immunocytochemical studies.

Cytochemical and immunocytochemical studies were performed on bone marrow aspirates from 96 cases of primary myelodysplastic syndrome (MDS), 11 cases of secondary MDS, 22 cases of non-MDS hematologic disorders, and 10 cases of nondiagnostic, apparently normal marrow specimens to determine the practicality and utility of these stains for diagnosing MDS. Cytochemical studies included iron stain, periodic acid-Schiff (PAS), peroxidase, butyrate esterase, chloroacetate esterase, and double esterase stains. Immunocytochemical staining was done with monoclonal antibody HP1-1D, which recognizes the glycoprotein IIb/IIIa complex in megakaryocytes. The iron stain remained most helpful in identifying abnormal ringed sideroblasts, a feature of dyserythropoiesis, and thus in supporting the diagnosis of MDS. The PAS stain was helpful, if positive, in identifying patients with MDS; however, when it was negative, this stain did not help distinguish MDS from non-MDS hematologic disorders. The immunocytochemical stain with HP1-1D monoclonal antibody was also helpful in identifying atypical micromegakaryocytes, indicative of dysmegakaryopoiesis. Other cytochemical abnormalities were infrequently observed and were less specific for the diagnosis of MDS. The combination of two stains--for example, PAS and iron stain or PAS and double esterase--was helpful, however, in excluding MDS, inasmuch as neither the miscellaneous nor the control group stained positively with these combinations.

Sarcomatoid salivary duct carcinoma of the parotid gland.

Salivary duct carcinoma (SDC) is a high-grade neoplasm known to histologically resemble high-grade ductal carcinoma in situ of the breast. We describe 3 cases of sarcomatoid salivary duct carcinoma, a heretofore unreported variant of SDC. Each case was a composite of SDC and sarcomatoid carcinoma and histologically similar to reported cases arising in the breast. The clinicopathologic features, including immunohistochemistry, of 3 cases were investigated. In the 3 men, ages 56, 68, and 70 years, the resected parotid tumors measured 1.5, 3.5, and 1.5 cm, respectively. Only the 3.5-cm tumor extended beyond the parotid gland into soft tissue. This patient died at 3 years with pulmonary metastases. The other patients were free of disease at 6 and 12 months. Histologically, each case was a composite of usual-type SDC and sarcomatoid carcinoma. SDC showed typical cribriform architecture, whereas anaplastic, spindled cells constituted the sarcomatoid areas. Immunohistochemically, epithelial elements stained as follows: cytokeratin (AE1/AE3 & CAM 5.2) positive in 3 of 3 cases, EMA positive in 3 of 3 cases, vimentin negative in 3 of 3 cases, desmin negative in 3 of 3 cases, c-erbB-2 positive in 1 of 2 cases. Sarcomatoid elements stained as follows: AE1/AE3 negative in 3 of 3 cases, CAM 5.2 rare positive cell in 1 of 3 cases, EMA focally positive in 3 of 3 cases, vimentin positive in 3 of 3 cases, desmin negative in 3 of 3 cases, c-erbB-2 negative in 2 of 2 cases. Electron microscopy, performed in one case, showed scattered junctional complexes congruent with epithelial differentiation. Immunohistochemical results, EMA and CAM 5.2 positivity, and ultrastructural findings supported our belief that these unique biphasic tumors represented SDC with sarcomatoid carcinoma. We conclude an element of sarcomatoid carcinoma rarely may arise in association with SDC, and it is erroneous to diagnose such tumors as "carcinosarcoma."

Extrarenal Wilms' tumor with cerebellar metastasis in a four-year-old girl with spina bifida.

This report documents the occurrence of an extrarenal nephroblastoma from which a cerebellar metastasis developed in a four-year-old girl with spina bifida. The second tumor became symptomatic two years after the resection of the primary, suggesting a treatment effect as a factor for the delay in the growing of the metastatic neoplasm. Histologic and ultrastructural features of the metastasis were similar to those described in Wilms' tumors of the kidney. The pathogenesis of this exceptional association, including malformation, malignancy, and unusual site of metastasis, is discussed.

Signet-ring cell carcinoma of the breast: a clinicopathologic study of 24 cases.

Twenty-four cases of signet-ring cell carcinoma of the breast are presented. These represented 4.5% of 535 cases of surgically treated breast cancer at Indiana University Medical Center. Twelve cases were associated with ductal carcinoma, nine with lobular carcinoma, one with colloid carcinoma, and four were pure signet-ring cell carcinoma. The mortality rate, incidence of axillary lymph nodal metastases, and number of involved lymph nodes were greater in cases of signet-ring cell carcinoma than with other forms of mammary carcinomas without signet-ring cells. It is proposed that signet-ring cell carcinoma can manifest as a pure lesion or as a variant of ductal, lobular, or colloid carcinoma, and that it is an aggressive histologic variant of mammary carcinoma.

Flow cytometric immunophenotypic characterization of pediatric and adult minimally differentiated acute myeloid leukemia (AML-M0).

We reviewed the clinicopathologic and immunophenotypic profiles of 7 pediatric and 11 adult minimally differentiated acute myelogenous leukemias (AML-M0). We also compared and evaluated myeloperoxidase in leukemic blasts using standard cytochemical and polyclonal antibody immunohistochemical stains. No distinctive clinical findings were noted in either patient group; however, thrombocytopenia typically was more prominent in adults. Adult AML-M0 also was associated with an immature myeloid profile (CD34+, terminal deoxynucleotidyl transferase positive, CD13+, and CD33+), in contrast with pediatric AML-M0, which usually lacked terminal deoxynucleotidyl transferase or CD34 but expressed bright CD33 with weak or negative CD13. Coexpression of the T-cell-associated antigen CD7 was observed in both groups. Antibody immunohistochemical stains were more sensitive than cytochemical stains for detection of myeloperoxidase activity and a useful adjunct for establishing a diagnosis of myeloid leukemia in paraffin-embedded marrow tissues.

Hypercalcaemia due to hyperparathyroidism in a patient with chronic renal failure and renal carcinoma.

A 65-year-old woman with a history of a left heminephrectomy for renal carcinoma developed hypercalcaemia 11 years after the operation. The same kidney was found to contain a recurrent renal carcinoma. After the radical nephrectomy of the left kidney, hypercalcaemia remitted but reappeared 11 months later. The right kidney was small but functioned at a level of creatinine clearance of 10--15 ml/min. Metastatic work-up was negative, and secondary causes of hypercalcaemia were excluded. A neck exploration revealed a parathyroid adenoma. With parathyroid resection the serum calcium declined to normal, and the risk of hypercalcaemic nephropathy in the remaining kidney was precluded.