Neurogenic inflammation of Guinea-pig bladder

Capsaicin, substance P, and ovalbumin, instilled into the bladders of naive and ovalbumin (OVA) sensitized guineapigs caused inflammation, as indicated by increased vascular permeability. Histological changes after exposure to these compounds progressed with time from intense vasodilatation to marginalization of granulocytes followed by interstitial migration of leukocytes. In vitro incubation of guinea-pig bladder tissue with substance P and ovalbumin stimulated release of prostaglandin D(2) and leukotrienes. In vitro incubation of bladder tissue with capsaicin, OVA, prostaglandin D(2), leukotriene C(4), histamine, or calcium ionophore A-23587 all stimulated substance P release. These data suggest that bladder inflammation initiated by a variety of stimuli could lead to a cyclic pattern of release of inflammatory mediators and neuropeptides, which could result in amplification and persistence of cystitis after the inciting cause has subsided.     

Autosomal recessive ichthyosis with hypotrichosis caused by a mutation in ST14, encoding type II transmembrane serine protease matriptase

In this article, we describe a novel autosomal recessive ichthyosis with hypotrichosis syndrome, characterized by congenital ichthyosis associated with abnormal hair. Using homozygosity mapping, we mapped the disease locus to 11q24.3-q25. We screened the ST14 gene, which encodes matriptase, since transplantation of skin from matriptase(-/-)-knockout mice onto adult athymic nude mice has been shown elsewhere to result in an ichthyosislike phenotype associated with almost complete absence of erupted pelage hairs. Mutation analysis revealed a missense mutation, G827R, in the highly conserved peptidase S1-S6 domain. Marked skin hyperkeratosis due to impaired degradation of the stratum corneum corneodesmosomes was observed in the affected individuals, which suggests that matriptase plays a significant role in epidermal desquamation.     

Mandatory role of proteinase-activated receptor 1 in experimental bladder inflammation

Background  

In general, inflammation plays a role in most bladder pathologies and represents a defense reaction to injury that often times is two edged. In particular, bladder neurogenic inflammation involves the participation of mast cells and sensory nerves. Increased mast cell numbers and tryptase release represent one of the prevalent etiologic theories for interstitial cystitis and other urinary bladder inflammatory conditions. The activity of mast cell-derived tryptase as well as thrombin is significantly increased during inflammation. Those enzymes activate specific G-protein coupled proteinase-activated receptors (PAR)s.     

Antifungal, phytotoxic and insecticidal properties of essential oil isolated from Turkish Origanum acutidens and its three components, carvacrol, thymol and p-cymene

The chemical composition of essential oil isolated by hydrodistillation from the aerial parts of Origanum acutidens was analyzed by GC-MS. Carvacrol (87.0%), p-cymene (2.0%), linalool acetate (1.7%), borneol (1.6%) and beta-caryophyllene (1.3%) were found to be as main constituents. Antifungal, phytotoxic and insecticidal activities of the oil and its aromatic monoterpene constituents, carvacrol, p-cymene and thymol were also determined. The antifungal assays showed that O. acutidens oil, carvacrol and thymol completely inhibited mycelial growth of 17 phytopathogenic fungi and their antifungal effects were higher than commercial fungicide, benomyl. However, p-cymene possessed lower antifungal activity. The oil, carvacrol and thymol completely inhibited the seed germination and seedling growth of Amaranthus retroflexus, Chenopodium album and Rumex crispus and also showed a potent phytotoxic effect against these plants. However, p-cymene did not show any phytotoxic effect. Furthermore, O. acutidens oil showed 68.3% and 36.7% mortality against Sitophilus granarius and Tribolium confusum adults, respectively. The findings of the present study suggest that antifungal and herbicidal properties of the oil can be attributed to its major component, carvacrol, and these agents have a potential to be used as fungicide, herbicide as well as insecticide.     

Parasitic Bacteria and Fungi on Common Mistletoe (Viscum album L.) and Their Potential Application in Biocontrol

This study was carried out to identify pathogenic bacteria and fungi on mistletoe (Viscum album L.) and investigate their potential use in biological control of this parasitic plant. For this purpose, a total of 48 fungal isolate and 193 bacterial strains were isolated from contaminated V. album during the summers 2005–2006. The isolated bacterial strains and fungal isolates were identified by using the Sherlock Microbial Identification System (MIS; Microbial ID, Newark) and microscopic methods, respectively. The bacterial strains that induced hypersensitive reaction (HR) on tobacco (Nicotiana tabacum L.) and fungal isolates were tested for pathogenicity on young shoots of mistletoe by using injection methods. The pathogenic bacterial strains and fungal isolates were also tested for their activity against mistletoe using spray methods. Five bacterial strains (two Burkholderia cepacia, one each of Bacillus megaterium, Bacillus pumilus and Pandoraea pulminicola) were HR and pathogenicity positive when injected but none of them when sprayed on mistletoe. When fungi were injected, 32 isolates were pathogenic but only thirteen when sprayed on mistletoe. Alternaria alternata VA?‐202, VA?‐205, VA?‐217 and Acremonium kiliense VA‐11 fungal isolates were the most effective ones and caused strong disease symptoms on mistletoe. The present study is the first report on the efficiency of potential biocontrol agents against mistletoe in Turkey.     

Antifungal and Herbicidal Effects of Fruit Essential Oils of Four Myrtus communis Genotypes

The chemical composition of the essential oils isolated by hydrodistillation from the fruits of four selected Myrtus communis L. genotypes from Turkey was characterized by GC‐FID and GC/MS analyses. 1,8‐Cineole (29.20–31.40%), linalool (15.67–19.13%), α‐terpineol (8.40–18.43%), α‐pinene (6.04–20.71%), and geranyl acetate (3.98–7.54%) were found to be the major constituents of the fruit essential oils of all M. communis genotypes investigated. The oils were characterized by high amounts of oxygenated monoterpenes, representing 73.02–83.83% of the total oil compositions. The results of the fungal growth inhibition assays showed that the oils inhibited the growth of 19 phytopathogenic fungi. However, their antifungal activity was generally lower than that of the commercial pesticide benomyl. The herbicidal effects of the oils on the seed germination and seedling growth of Amaranthus retroflexus L., Chenopodium album L., Cirsium arvense (L.) Scop ., Lactuca serriola L., and Rumex crispus L. were also determined. The oils completely or partly inhibited the seed germinations and seedling growths of the plants. The findings of the present study suggest that the M. communis essential oils might have potential to be used as natural herbicides as well as fungicides.     

Are we aware how contaminated our mobile phones with nosocomial pathogens?

Vibrio spp. is a pathogen rarely isolated in cancer patients, and in most cases it is associated with haematological diseases. Cutaneous manifestations of this organism are even rarer. We report a case of Non-O1 Vibrio cholerae inguinal skin and soft tissue infection presenting bullous skin lesions in a young type II diabetic patient with a penis squamous cell carcinoma having a seawater exposure history.     

Signalling mechanisms regulating phenotypic changes in breast cancer cells

In MCF-7 breast cancer cells epidermal growth factor (EGF) induces cell proliferation, whereas heregulin (HRG)/neuregulin (NRG) induces irreversible phenotypic changes accompanied by lipid accumulation. Although these changes in breast cancer cells resemble processes that take place in the tissue, there is no understanding of signalling mechanisms regulating it. To identify molecular mechanisms mediating this cell-fate decision process, we applied different perturbations to pathways activated by these growth factors. The results demonstrate that phosphoinositide 3 (PI3) kinase (PI3K) and mammalian target of rapamycin (mTOR) complex (mTORC)1 activation is necessary for lipid accumulation that can also be induced by insulin, whereas stimulation of the extracellular-signal-regulated kinase (ERK) pathway is surprisingly dispensable. Interestingly, insulin exposure, as short as 4 h, was sufficient for triggering the lipid accumulation, whereas much longer treatment with HRG was required for achieving similar cellular response. Further, activation patterns of ATP citrate lyase (ACLY), an enzyme playing a central role in linking glycolytic and lipogenic pathways, suggest that lipids accumulated within cells are produced de novo rather than absorbed from the environment. In the present study, we demonstrate that PI3K pathway regulates phenotypic changes in breast cancer cells, whereas signal intensity and duration is crucial for cell fate decisions and commitment. Our findings reveal that MCF-7 cell fate decisions are controlled by a network of positive and negative regulators of both signalling and metabolic pathways.     

The second coordination sphere of FIH controls hydroxylation

The factor inhibiting HIF (FIH) is a proximate oxygen sensor for human cells, hydroxylating Asn(803) within the α-subunit of the hypoxia inducible factor (HIF). FIH is an α-ketoglutatrate (αKG)-dependent, non-heme Fe(II) dioxygenase, in which Fe(II) is coordinated by a (His(2)Asp) facial triad, αKG, and H(2)O. Hydrogen bonding among the facial triad, the HIF-Asn(803) side chain, and various second-sphere residues suggests a functional role for the second coordination sphere in tuning the chemistry of the Fe(II) center. Point mutants of FIH were prepared to test the functional role of the αKG-centered (Asn(205) and Asn(294)) or HIF-Asn(803)-centered (Arg(238) and Gln(239)) second-sphere residues. The second sphere was tested for local effects on priming Fe(II) to react with O(2), oxidative decarboxylation, and substrate positioning. Steady-sate kinetics were used to test for overall catalytic effects; autohydroxylation rates were used to test for priming and positioning, and electronic spectroscopy was used to assess the primary coordination sphere and the electrophilicity of αKG. Asn(205) → Ala and Asn(294) → Ala mutants exhibited diminished rates of steady-state turnover, while minimally affecting autohydroxylation, consistent with impaired oxidative decarboxylation. Blue-shifted metal to ligand charge transfer transitions for (Fe+αKG)FIH indicated that these point mutations destabilized the π* orbitals of αKG, further supporting a slowed rate of oxidative decarboxylation. The Arg(238) → Met mutant exhibited steady-state rates too low to measure and diminished product yields, suggesting impaired substrate positioning or priming; the Arg(238) → Met mutant was capable of O(2) activation for the autohydroxylation reaction. The Gln(239) → Asn mutant exhibited significantly slowed steady-state kinetics and diminished product yields, suggesting impaired substrate positioning or priming. As HIF binding to the Gln(239) → Asn mutant stimulated autohydroxylation, it is more likely that this point mutant simply mispositions the HIF-Asn(803) side chain. This work combines kinetics and spectroscopy to show that these second-sphere hydrogen bonds play roles in promoting oxidative decarboxylation, priming Fe(II) to bind O(2), and positioning HIF-Asn(803).