Resistance to hypertension and high Cl- excretion in humans with SLC26A4 mutations.

Pendrin is a membrane transporter encoded by solute carrier family26A4 (SLC26A4). Mutations in this gene are known to cause hearing loss, and recent data from animal studies indicate a link between pendrin expression and hypertension; although, this association in humans is unclear. To clarify this issue, we investigated the influence of pendrin on blood pressure by analyzing demographic and biochemical data - including blood pressure and urinary electrolyte excretion - in patients with bi-allelic SLC26A4 mutations. Systolic and diastolic blood pressure and the left ventricular hypertrophy index were lower in subjects with pendrin mutations than in controls. In addition, fractional excretion of Na+ and Cl- was increased and serum renin, angiotensin I and II levels were higher in subjects with pendrin mutations as compared to controls. Thus, patients with impaired pendrin function are likely to be resistant to high blood pressure due to enhanced urinary Na+ /Cl- excretion. These results suggest that pendrin may regulate blood pressure through increased urinary salt excretion.

Natural extracellular matrix scaffolds recycled from human salivary digests: a morphometric study.

OBJECTIVE: A challenge in engineering tissues is to supply parenchymal cells with suitable scaffolds which ideally reproduce the extracellular matrix (ECM). This study tested the hypothesis of preserving the 'residual connective tissue' remaining after mechanical and enzymatic release of cells from human submandibular gland biopsies (that we named 'natural ExtraCellular Matrix scaffolds', nECMsc) to be used as recycled natural scaffolds. The objective was to test whether nECMsc and native salivary tissue were comparable morphologically, in ECM proteins composition, and in cell seeding efficiency. METHODS: Following cell isolation procedures, nECMsc were kept, either fresh or frozen (sectioned into 12-µm-thick slices), and examined with high-resolution electron microscopy (HRSEM) for its three-dimensional structure, and with picrosirius red staining and immunogold staining for ECM protein composition and distribution, respectively. nECMsc were seeded with human epithelial cells and fibroblasts to assess cell attachment and proliferation in short-term experiments. RESULTS: Under HRSEM, nECMsc had comparable fiber arrangement to original glands. Histochemical and immunogold-labeling examinations revealed the presence of collagen types I, III, and IV. Seeded epithelial cells and fibroblasts attached, proliferated (14-55%), and were alive (86-99%) after 4-8 days of culture. CONCLUSIONS: nECMsc retained native ECM proteins and maintained their distribution. Seeded cells remained viable on nECMsc.

Effect of antihistamine as an adjuvant treatment of isotretinoin in acne: a randomized, controlled comparative study.

BACKGROUND: Isotretinoin has been frequently used for acne therapy. However, it has limitation in acceptance because of its adverse effects. Although antihistamine recently revealed to decrease the lipogenesis, evidence is lacking regarding the clinical relevance of antihistamine in the treatment of acne. OBJECTIVES: To evaluate the clinical efficacy and tolerability of antihistamine as an adjuvant treatment of isotretinoin. METHODS: Forty patients with moderate acne were included in this randomized, controlled comparative study. Twenty patients were treated with isotretinoin and 20 patients were treated with additional antihistamine, desloratadine. Assessment was made at baseline, after 2, 4, 8 and 12 weeks of treatment. RESULTS: At week 12, compared with isotretinoin only group, isotretinoin with additional antihistamine group showed more statistically significant decrease in acne lesion counts (non-inflammatory lesions: 44.8% vs. 17.8%; inflammatory lesions: 55.8% vs. 22.9%; total lesions: 45.6% vs. 18.7%; all P < 0.05). Significant decrease was also observed in the score of global acne grading system and the measured value of sebum and erythema. Moreover, acne flare during the treatment occurred less frequently and adverse events of isotretinoin were more tolerable in additional antihistamine group. CONCLUSIONS: This results provide early evidence that antihistamine has a synergic effect with minimizing the side-effect of isotretinoin, and may be used as an adjuvant treatment of moderate acne.

Proton pump inhibitors as a possible cause of vitiligo: an in vivo and in vitro study.

BACKGROUND: Vitiligo is an acquired depigmentation disorder of melanocytes. Recently, some clinical reports have suggested that proton pump inhibitors (PPIs) may worsen vitiligo, but their effects on melanocytes have yet to be elucidated. OBJECTIVE: We investigated the effect of PPIs on melanogenesis in vivo and in vitro. METHODS: We examined the effect of PPIs on melanogenesis in B16 murine melanoma cells by measuring melanin content and tyrosinase (TYR) activity. TYR and tyrosinase-related protein-1 (TRP-1) were monitored by western blotting. Finally, a PPI was applied to zebrafish embryos to investigate its in vivo effect on pigmentation. RESULTS: In agreement with our clinical experience of worsened vitiligo after PPI treatment, PPIs decreased both melanin content and TYR activity. Western blotting showed that PPIs decreased TYR and TRP-1 protein levels. In the zebrafish test, PPIs inhibited body pigmentation in a dose-dependent manner. CONCLUSION: These results suggest that the functional inhibition of melanization by PPIs may induce or aggravate vitiligo lesions in genetically predisposed patients.

Morphological studies of SnO2 thin films fabricated by using e-beam method.

This paper studies the variations in morphology of SnO2 nanostructures thin films deposited by using e-beam technique with the substrate temperature, oxygen partial pressure and the film thickness. The e-beam conditions were optimized to get crystalline nanosheets of SnO2. The films of 100-700 nm thickness were deposited on quartz substrates at temperatures ranging from room temperature (RT) to 300 degrees C and oxygen partial pressure ranging from 0 to 200 sccm. The nanostructured films have been characterized by means of X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM) and Energy dispersive spectroscopy (EDS) measurements. XRD results show that the films deposited at RT and 100 degrees C were amorphous, however, for 200 degrees C and 300 degrees C, the films showed crystalline nature with rutile structure. Also, the crystallinity increased with the increase of oxygen partial pressure. FE-SEM images revealed that at RT and 100 degrees C of substrate temperature, the film consist of spherical particles, whereas, the films deposited at 200 degrees C and 300 degrees C consist of sheet like morphology having thickness -40 nm and lateral dimension of 1 microm, respectively. The size of the nanosheets increased with the increase of substrate temperature and oxygen partial pressure due to the enhancement in the crystallinity of the films. A possible growth mechanism of the formation of SnO2 nanosheets is discussed.

Clinical characteristics and risk of melanoma development from giant congenital melanocytic naevi in Korea: a nationwide retrospective study.

BACKGROUND: Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated. OBJECTIVES: To evaluate the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥5% body surface area in children or measuring ≥20cm in adults. METHODS: In total, 131 patients with GCMN were enrolled, with a mean age of 10·3years (range: birth-70years). RESULTS: The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients <4years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6-year-old girl, a 14-year-old girl and a 70-year-old man), and the incidence rate was 990 per 100000 person-years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma. CONCLUSIONS: We should be aware of melanoma development from GCMN, and lifelong follow-up is required due to the risk of melanoma arising in GCMN.

Effects of the estrous cycle and pregnancy status on cardiovascular variables in healthy bitches.

INTRODUCTION: The aim of the study was to characterize changes in maternal cardiovascular variables throughout the reproductive cycle in healthy bitches and determine whether magnitude of pregnancy-induced changes correlates to litter size. ANIMALS: Eleven client-owned breeding bitches were included in the study. MATERIALS AND METHODS: Bitches were enrolled prospectively and followed up longitudinally throughout a single reproductive cycle. Physical examination, echocardiography, blood pressure analysis, and plasma volume estimation were performed during proestrus, diestrus (early and late pregnancy), and anestrus. Fetal echocardiography was performed during late pregnancy. Data were compared across visits using a linear mixed-effects model, and correlation between variables was assessed. RESULTS: Compared with proestrus, no significant changes were observed at any phase of the cycle in heart rate, blood pressure, echocardiographic measurements of left ventricular size or function, or echocardiographic calculations of stroke volume or cardiac output. Estimated plasma volume increased by 29.6% in early pregnancy (p < 0.001) and 70.7% in late pregnancy (p < 0.001). Fetal echocardiography was feasible in a subset of fetuses for each bitch. There was a significant correlation between estimated total fetal cardiac output and late pregnancy increase in maternal cardiac output (p = 0.0025). The incidence of physiologic heart murmurs ranged from 5 of 11 (45%) bitches in proestrus to 2 of 11 (18%) bitches in late pregnancy, attributed to variations in aortic outflow velocity. CONCLUSIONS: Hemodynamic alterations in pregnant bitches do not result in consistently detectable echocardiographic changes, suggesting that cardiac screening could be diagnostic at any time during a reproductive cycle. Physiologic heart murmurs were common in this study population and not obviously associated with the reproductive cycle.

Cutaneous lymphangiectasia associated with photoageing and topical corticosteroid application.

We report the case of a 69-year-old man with a history of multiple erythematous bullae on both forearms, which had been present for about 1 month. The lesions appeared after several years of topical corticosteroid application and photoageing. A biopsy revealed lymphangiectasia with solar elastosis and increase in the ratio of elastic to collagen fibres in the dermis. We suggest that this patient's lymphangiectasia resulted from abnormal structure and function of the dermis due to photoageing and steroid-related atrophy.

Characterization of the hypothalamic proopiomelanocortin gene and beta-endorphin expression in the hypothalamic arcuate nucleus of mice elicited by inflammatory pain.

We examined proopiomelanocortin (POMC) mRNA and beta-endorphin expression in the hypothalamus of mice after various nociceptive stimuli. The time-course study (10 min, 30 min, 1 h, 2 h, and 10 h) showed that the POMC mRNA level significantly increases from 1 h after s.c. formalin injection and returns to the control level at 10 h. Intrathecal (i.t.) substance P (SP) injection also increases the hypothalamic POMC mRNA level from 1 h to 10 h. However, i.t. glutamate injection did not affect the hypothalamic POMC gene expression at all time points. We found that the POMC mRNA after s.c. formalin injection was located in the arcuate nucleus of the hypothalamus. In the same manner, beta-endorphin immunoreactivity was also increased in the hypothalamic arcuate nucleus. The expression of phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK1/2), phosphorylated calcium/calmodulin-dependent protein kinase-IIalpha (pCaMK-IIalpha) protein and phosphorylated IkappaB (pIkappaB) protein was increased by s.c. formalin injection at various time points. We also found that increased pERK1/2, pCaMKIIalpha and pIkappaB protein after s.c. formalin injection was mainly located in the arcuate nucleus of hypothalamus in which cells containing beta-endorphin after s.c. formalin injection also express pERK1/2, pCaMK-IIalpha and pIkappaB immunoreactivity. In addition, formalin-induced POMC mRNA expression was significantly reduced by 10 min, pretreatment with i.c.v. PD98059 (mitogen-activated protein kinase (MAPK) pathways inhibitor; 6.6 mug) and KN93 (pCaMK-II inhibitor; 20 mug). In conclusion, POMC mRNA expression in the arcuate nucleus of the hypothalamus was increased by inflammatory pain stimuli, in which pERK1/2, pCaMK-IIalpha and NFkappaB may play an important role in the expression of the hypothalamic POMC gene and beta-endorphin expression.

Differential expression of phosphorylated Ca2+/calmodulin-dependent protein kinase II and phosphorylated extracellular signal-regulated protein in the mouse hippocampus induced by various nociceptive stimuli.

In the present study, we characterized differential expressions of phosphorylated Ca(2+)/calmodulin-dependent protein kinase IIalpha (pCaMKIIalpha) and phosphorylated extracellular signal-regulated protein (pERK) in the mouse hippocampus induced by various nociceptive stimuli. In an immunoblot study, s.c. injection of formalin and intrathecal (i.t.) injections of glutamate, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1 beta) significantly increased pCaMKIIalpha expression in the hippocampus, but i.p. injections of acetic acid did not. pERK1/2 expression was also increased by i.t. injection of glutamate, TNF-alpha, and IL-1beta but not by s.c. injections of formalin or i.p. injections of acetic acid. In an immunohistochemical study, we found that increased pCaMKIIalpha and pERK expressions were mainly located at CA3 or the dentate gyrus of the hippocampus. In a behavioral study, we assessed the effects of PD98059 (a MEK 1/2 inhibitor) and KN-93 (a CaMKII inhibitor) following i.c.v. administration on the nociceptive behaviors induced by i.t. injections of glutamate, pro-inflammatory cytokines (TNF-alpha or IL-1beta), and i.p. injections of acetic acid. PD98059 as well as KN-93 significantly attenuated the nociceptive behavior induced by glutamate, pro-inflammatory cytokines, and acetic acid. Our results suggest that (1) pERKalpha and pCaMK-II located in the hippocampus are important regulators during the nociceptive processes induced by s.c. formalin, i.t. glutamate, i.t. pro-inflammatory cytokines, and i.p. acetic acid injection, respectively, and (2) the alteration of pERK and pCaMKIIalpha in nociceptive processing induced by formalin, glutamate, pro-inflammatory cytokines and acetic acid was modulated in a different manner.

The effect of formalin pretreatment on nicotine-induced antinociceptive effect: the role of mu-opioid receptor in the hippocampus.

Nicotine is attractive as an analgesic component despite that its antinociceptive mechanism is not well known until now. In the present study, we examined the antinociceptive effect of nicotine administered supra-spinally on acetic acid-induced visceral pain induction (writhing test), and found that the antinociceptive effect of nicotine was abolished by mu-, delta-, and kappa-opioid receptor antagonist administered i.c.v. In addition, s.c. 5% formalin pretreatment at 5 h, 20 h, 40 h, and 1 week prior to i.c.v. nicotine injection abolished the antinociceptive effect of nicotine in the writhing test, suggesting that s.c. formalin pretreatment induced tolerance to the antinociceptive effect of nicotine in the supra-spinal region. Furthermore, neuronal loss of the hippocampal cornus ammonis (CA) 3 region reduced nicotine-induced an antinociceptive effect in the writhing test. In Western blot assay, we examined s.c. formalin injection down-regulated mu-opioid receptor in the hippocampus after 40 h, and its effect was maintained for 1 week. However, various acetylcholine receptor subunits and delta-, and kappa-opioid receptors were not altered. These results suggest that s.c. formalin pretreatment can contribute to induce tolerance on nicotine-induced antinociception as down-regulating mu-opioid receptor in the hippocampus, especially 40 h after s.c. formalin injection.

Surgical outcomes of tympanoplasty using a sterile acellular dermal allograft: a prospective randomised controlled study.

Acellular human dermal allografts have been shown to be effective for soft-tissue implantation. We compared treatment outcomes of tympanoplasty using tragal perichondrium and acellular human dermal allograft (MegaDerm®). In a prospective randomised controlled study, 60 patients scheduled to undergo tympanoplasty were randomly assigned to the autologous tragal perichondrium group (n = 33) or acellular human dermal allograft group (n = 27). Postoperative hearing gain, graft success rate at 1 and 6 months and operation times were compared between groups. Graft success rate, defined as the complete closure of tympanic membrane perforation, did not show any significant intergroup difference (75.8% vs 85.2%, p = 0.519). Air conduction thresholds and air-bone gaps showed significant improvements in both groups; from 38.7 ± 15.9 dB to 30.2 ± 15.6 dB (p < 0.001) and from 17.8 ± 7.3 dB to 11.5 ± 7.0 (p = 0.001) in the autologous tragal perichondrium group, and from 30.4 ± 12.2 dB to 24.5 ± 13.0 dB (p = 0.006) and from 14.3 ± 5.1 dB to 7.6 ± 4.6 dB (p < 0.001) in the acellular human dermal allograft group. The amount of hearing gain (p = 0.31) and closure of air-bone gap (p = 0.863) were not meaningfully different between groups. The mean operation time was significantly lower in the acellular human dermal allograft group (35.2 min vs 27.4 min, p = 0.039). In this prospective randomised controlled study, acellular human dermal allograft was shown to be an effective alternative to tragal perichondrium, with similar graft success rates and postoperative hearing results, but with reduced operation times.

The effect of single or repeated restraint stress on several signal molecules in paraventricular nucleus, arcuate nucleus and locus coeruleus.

The effect of single or repeated restraint stress on several signal molecules in the hypothalamus was studied in ICR mice. Single restraint stress was induced for 30, 60, and 120 min. A repeated restraint stress was induced for 2 h daily during four consecutive days, and then induced in the same time course on the fifth day. In the immunoblot assay, we observed that the signal molecules c-Fos, phosphorylated extracellular cell-regulated protein kinase (pERK), phosphorylated calcium/calmodulin dependent protein kinase II (pCaMKII) and phosphorylated cyclic-AMP response element binding protein (pCREB) in the hypothalamus were increased by single restraint, and the increased c-Fos and pERK levels were attenuated by repeated restraint stress. However, pCaMKII and pCREB levels were increased by both single and repeated restraint stress. We also observed in the immunohistochemistry study that immunoreactivities (IR) of these signal molecules were changed in paraventricular (PVN) and arcuate nuclei (ArcN) of the hypothalamus in accordance with immunoblot results. Furthermore, in confocal immunofluorescence, the pCaMKII and pCREB up-regulated by repeated restraint stress were co-localized within many neurons of PVN and ArcN. In addition, we found that c-Fos and pCaMKII IR in locus coeruleus (LC) were increased by single restraint, and were attenuated by repeated restraint stress. However, the pERK and pCREB IR were increased by both single and repeated restraint stress. The confocal study revealed that pERK and pCREB up-regulated by repeated restraint stress were co-localized within many neurons of LC. Our results suggest that single and repeated restraint stress differentially triggers the induction and phosphorylation of several signal molecules in the PVN, ArcN, and LC. In addition, single and repeated stress stimuli elicited the brain-region specific changes of signal molecules examined. Furthermore, the upstream signal molecule activating CREB may be also brain-region specific, especially in repeated stress stimuli.

Management of Meloidogyne incognita on tomato by root-dip treatment in culture filtrate of the blue-green alga, Microcoleus vaginatus.

The nematicidal potential of culture filtrates of the blue-green alga, Microcoleus vaginatus (Cyanobacterium) was tested against Meloidogyne incognita on tomato in pots under greenhouse conditions. Prior to the transplantation of tomato seedling, roots were dipped in different concentrations (0.2%, 0.5%, 1%, 2%, 10%, 50% and 100%) of culture filtrate of M. vaginatus for 30 min. Root-dip treatment reduced the root galling and final population of M. incognita and increased vegetative growth of plants and root-mass production compared with the control. The beneficial effect of root-dip treatment increased with the increase in the concentration of culture filtrate. Root galling and final nematode populations were reduced by 65.9% and 97.5%, respectively when treated at the highest concentration.

Malignant hidroacanthoma simplex: a case report.

Hidroacanthoma simplex is a benign tumor of the skin originating from or showing differentiation to the sweat glands. It grossly resembles seborrheic keratosis of Bowen's disease and histologically shows intraepidermal focal growth of epithelial cells. Malignant transformation of this tumor is rare. We report a case of pigmented hidroacanthoma with malignant transformation in a 67-year-old woman. There was a 20-year history of a skin lesion on the right thigh, which first appeared as a small verrucous papule, progressed to a dark-brown colored patch, and then to a pigmented plaque. Histologically, the primary tumor was composed of small squamoid cells with marked cellular atypia. Most of the tumor cells were located in the epidermis. Immunohistochemically, the cytoplasm of some tumor cells showed a positive reaction for epithelial membrane antigen, but not for either carcino-embryonic antigen or the S-100 protein.

The effect of lectin from Taro tuber (Colocasia antiquorum) given by force-feeding on the growth of mice.

In earlier experiments in our laboratory, a lectin from the Kintoki bean (Phaseolus vulgaris) was found to have not only erythrocyte agglutinating activity but also toxicities for mice and rats, including growth inhibitory activity and even lethal activity. A number of studies on legume lectins have been carried out in other laboratories as well. But relatively little attention has been paid to lectins from non-leguminous foods. In the present study, we chose Taro tuber as a source of non-leguminous lectins and prepared two types of Taro tuber lectin. One was crude lectin precipitated with ammonium sulfate from the aqueous extract and the other was pure lectin isolated as we described previously. The two were compared with regards to the antinutritional functions in mice. The daily doses were 100 mg for either intact or autoclaved crude lectin, which was a maximum amount available to give to mice in 1 ml, and 30 mg for the pure lectin which was equivalent to 100 mg of the crude lectin in hemagglutinating activity. Control mice were given 1 ml of water and the experiment was conducted for 6 days. Growth retardation was found in the mice given either lectin, but no significant difference was found in the weight increase between the control group and the autoclaved lectin group. For 3 days during the experimental period, physical activity was measured as an index of vigor of mice. The activities of the crude lectin and the pure lectin groups leveled down to 62.9 and 64.2% of that of the control group, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)