Summa sidvisningar

söndag 6 januari 2013

Onko Aladdinin tarinoita vai mitä tämä on?

Reza Kahlili niminen mies kirjoittaa:
"Länsivallat aiotaan saada polvilleen biologisin asein joita kehitellään radikaali-islamin uskonnon innoittaman hallituksen toimesta.iranin vallankumouksellisen kaartin jostakin lähteestä on tihkunut tieto, että iranilaiset, venäläiset ja P-korealaiset tiedemiehet yhdessä kehittelisivät  ainakin kahdeksaa erittäin vaarallista biologista agenssia mikrobia ja että tällainen laitos toimisi Marzanabad nimisessä laitoksessa  Iranissa . Mainitaan vielä lukumääriä alan venäläisistä ja iranilaisista tiedemiehistä. Jopa 18 eri ainetta olisi ohjelmassa ja neljä niistä valmiina kahdessa muussa laitoksessa olisi yhteensä kahdeksan mikrobiagenssia ohjelmissa ja menossa olisi vielä vektoritutkimukset: mikä ititkka voisi kuljettaa agenssia ja infektoida vihollisyhteiskuntia".

 Annan tuon  sitaatin olla vielä tuossa alla, mutta kommenttoin.
Suuria määriä ihmiskuntaa  surmaavat mikrobiainekset ovat lähinnä pandemian kaltaisia, ja luonnolla itsellään on todellakin kehittelemistä sellaisissa . Ihmiskunnasta iskee sitten yhteisesti kehkeytetty vastavoima joka tuhoaa yhteisen uhkan. On aika vaikeaa kehittää biologinen ase joka voisi surmata suurta osaa ihmiskuntaa, koska on olemassa se vastavoima kyky myös biologiselta taholta.  Mutta tietysti jos otetaan biologisen aseen myrkky ja synteettisesti tehdään sen myrkkyä, voi pahuuden valtaan joutunut osa ihmiskuntaa saada paljon kuolemaa aikaa  niissä, jotka ovat heitä parempia. Koska massatuho sinänsä on aika järjetöntä, monesti ne jotka kuolevat ovat niitä, jotka itse ovat valmistelemassa  noita myrkkyjä.

 KYSEENALAINEN SITAATTI:

"Iranian scientists, working under orders from the radicals running the Islamic regime, have genetically altered microbial agents in a nightmarish scheme to bring the West to its knees.
According to a source in the Revolutionary Guards intelligence unit with knowledge of Iran’s microbial research and development, the scientists, with Russian and North Korean help, currently possess eight extremely dangerous microbial agents that, if unleashed, could kill millions of people.Ne kahdeksan agenssia joista on kyse, mianitaan nimiltään:  anthrax, VEE  Venezuelan enkefaliitti virus, yellow grain, SARS, ebola, kolera, isorokko ja rutto.

The source revealed the existence of a plant in Marzanabad, Iran, where 12 Russian and 28 Iranian scientists are working on microbial agents for bombs. At that time, the source disclosed that Iran was working on 18 agents, with four completed. He has now provided information that with work at two other plants, Iran has created a total of eight microbial agents, with research on insects to be used as the vector to infect the societies of its enemies.

The eight agents are
  •  anthrax, 
  • encephalitis (the blueprint of this virus, Venezuelan Equine Encephalitis, was provided by Venezuelan President Hugo Chavez in an agreement two years ago with the Islamic regime),
  • yellow grain (developed with the help of North Korea),
  •  SARS, 
  • Ebola,
  • cholera,
  • smallpox and 
  • plague.
Iran, with North Korea’s help, has genetically altered the smallpox virus that makes current vaccinations useless against it. And research at two facilities that act as drug companies but are fronts for the deadly research shows insects can be used as the vector to carry plague, infamous as the “Black Death,” according to the source.
The outbreak of plague in the Middle Ages killed one-third of Europe’s population, and it resurfaced in the 19th century in Asia, killing millions in China and India.
The radicals ruling Iran believe their planned microbial attacks cannot be traced to them, the source said. Through various commerce channels and trade with Europe and even through Mexico into the U.S., the regime could release the infected insects and small rodents into populated cities, causing an epidemic that could possibly kill tens of millions of people, he said.
“The most dangerous biological weapons agents today are genetically modified or even synthetically created in a laboratory in ways that not only make them more contagious, infectious and lethal, but also are intended to defy existing vaccine countermeasures,” said Clare M. Lopez, a senior fellow at RadicalIslam.org and the Center for Security Policy, a non-profit, non-partisan think tank based in Washington, D.C. “Among such (biological weapons) agents are (genetically-modified) strains of anthrax, plague and smallpox.
“The open-source literature consistently describes Russia and North Korea as sources of such strains and the scientific know-how to create and deploy them,” Lopez said. “Likewise, Iran and Syria are reported to be among the recipients of such deadly (biological weapons) agents; each of these countries also has an extensive medical and pharmaceutical research and development infrastructure within which to produce (and also conceal) its BW programs. Both Iran and Syria also have shared not only these pathogens, but the artillery, ballistic missile and munitions technology with each other and, likely, with Hezbollah as well, for delivery of such pathogens.”
Lopez said that insects such as fleas, flies and mosquitoes long have been recognized as natural vectors for the spread of deadly diseases and that disease-bearing insects have been used in warfare for centuries, perhaps most notoriously by the Japanese during WW II against China, causing the death of hundreds of thousands. While cholera typically is not fatal if treated quickly, some strains can kill within hours. Bubonic plague has been the cause of some of the greatest pandemics in world history.
The Revolutionary Guards source added that the Islamic regime has already armed 37 of its ballistic missiles with microbial agents, which upon launch would spray targeted areas as opposed to an explosion. It has also armed cluster bombs with such agents, which could be dropped from fighter jets spraying an intended area.
What makes it worse, the source said, is that Hezbollah, Islamic Jihad and other terrorist proxies of the regime have now been armed with microbial weapons. As reported in the Washington Times in August, chemical and microbial weapons have been transferred to Iran’s proxies in the region.
The West, with its soft approach on the radical regime in Iran, has provided the needed time not only for it to arm itself with some of the most deadliest biological weapons but also, with the help of North Korea, to get the nuclear bomb, and, despite what the West believes, is now working to arm its missiles with such weapons of mass destruction, the source said".


Koleratoksiini ja munuainen

Pharmacol Toxicol. 1999 Sep;85(3):105-10. Glomerular effects of cholera toxin in isolated perfused rat kidney: a potential role for platelet activating factor.

Source

Department of Physiology and Pharmacology and Clinical Research Unit-HUWC/UFC-UECE, Faculty of Medicine, Federal University of Ceará, Brazil.

Abstract

Cholera toxin (MW 84 kDa) is now considered a pharmacological tool to study the adenylyl cyclase system and a stimulus to generate platelet activating factor in the intestinal tract. We used this toxin to evaluate the renal haemodynamics, glomerular filtration function, tubular sodium transport and toxicity in isolated perfused rat kidney. Kidneys from adult male Wistar rats were isolated for perfusion. The perfusion fluid was modified Krebs-Henseleit solution and the samples were analyzed for sodium, potassium, inulin and osmolality. Clearance techniques were used to calculate physiological parameters. Cholera toxin (1.0 microg/ml) caused a significant time-dependent reduction of glomerular filtration rate and urinary flow. This toxin also caused a small, but consistent reduction in fractional proximal sodium reabsortion (toxin = 67.43+/-2.42% versus control = 79.26+/-5.80%; P<0 .025=".025" 100="100" 2086="2086" 90="90" a="a" abolished="abolished" activating="activating" addition="addition" also="also" amp="0.26+/-0.01" and="and" antagonist="antagonist" are="are" at="at" b-cyclic="b-cyclic" blocked="blocked" but="but" by="by" caused="caused" cholera="cholera" completely="completely" contrast="contrast" control="0.145+/-0.02" db-cyclic="db-cyclic" decrease="decrease" dibutyryl-cyclic="dibutyryl-cyclic" effect="effect" effects="effects" factor.="factor." factor="factor" filtration="filtration" flow.="flow." flow="flow" fractional="fractional" functional="functional" g="g" glomerular="glomerular" had="had" in="in" increase="increase" increased="increased" induced="induced" injected="injected" integrity="integrity" isolated="isolated" it="it" kidney="kidney" kidneys.="kidneys." kidneys="kidneys" m="m" maximal="maximal" mediated="mediated" microg="microg" min.="min." min="min" ml="ml" more="more" n="8," no="no" of="of" on="on" only="only" or="or" p="p" parameters="parameters" perfusate="perfusate" perfused="perfused" perfusion="perfusion" platelet="platelet" potassium="potassium" previously="previously" primarily="primarily" proximal="proximal" rat="rat" rate="rate" reabsortion="reabsortion" receptor="receptor" reduction="reduction" remained="remained" renal="renal" resistance="resistance" results="results" severe="severe" significant="significant" significantly="significantly" similar="similar" sodium="sodium" stable="stable" suggest="suggest" suggesting="suggesting" that="that" the="the" this="this" throughout="throughout" time.="time." tissue="tissue" to="to" toxin.="toxin." toxin="toxin" treated="treated" urinary="urinary" vascular="vascular" versus="versus" was="was" web="web" when="when" with="with" x="x">

lördag 5 januari 2013

Koleratoksiinin vaikutusmekanismi

 Suomennan tähän koleratoksiinin mekanismista  myöhemmin.
Etsin  ADH:n ja PACAPin välistä säätelyä. Kolerassa  nesteen menetys voi olla kaksikymmnetä ( 20)  litraa päivässä  hypovyysitasossa voidaan vaikuttaa nesteen säästämiseen jos  PACAP( ylimmäinen  AC säätäjäentsyymi)  ja muut  AC-entsyymit voidaan jotenkin suojata kolaratoksiinilta, koska ne säätyvät  jatkuvasti päälle ja vaurio on irreversibeli.
FASEB J. 2006 Jan;20(1):130-2. Epub 2005 Nov 29.Luminally active, nonabsorbable CFTR inhibitors as potential therapy to reduce intestinal fluid loss in cholera.

Source

Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA.

Abstract

Enterotoxin-mediated secretory diarrheas such as cholera involve chloride secretion by enterocytes into the intestinal lumen by the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. We previously identified glycine hydrazide CFTR blockers that by electrophysiological studies appeared to block the CFTR anion pore at its lumen-facing surface. Here, we synthesize highly water-soluble, nonabsorbable malondihydrazides by coupling 2,4-disulfobenzaldehyde, 4-sulfophenylisothiocyante, and polyethylene glycol (PEG) moieties to 2-naphthalenylamino-[(3,5-dibromo-2,4-dihydroxyphenyl) methylene] propanedioic acid dihydrazide, and aminoacethydrazides by coupling PEG to [(N-2-naphthalenyl)-2-(2-hydroxyethyl)]-glycine-2-[(3,5-dibromo-2,4-dihydroxyphenyl) methylene] hydrazide. Compounds rapidly, fully and reversibly blocked CFTR-mediated chloride current with Ki of 2-8 microM when added to the apical surface of epithelial cell monolayers. Compounds did not pass across Caco-2 monolayers, and were absorbed by <2 added="added" blocked="blocked" by="by" compounds="compounds" hr="hr" in="in" intestine.="intestine." luminally="luminally" mouse="mouse">90% cholera toxin-induced fluid secretion in mouse intestinal loops, without inhibiting intestinal fluid absorption. These orally administered, nonabsorbable, nontoxic CFTR inhibitors may reduce intestinal fluid losses in cholera.

  • http://europepmc.org/abstract/MED/9310397

 Pituitary adenylate cyclase-activating polypeptide (PACAP) was localized in nerve terminals that innervate arginine-vasopressin (AVP)-containing neurons in the rat hypothalamic supraoptic nucleus (SON). PACAP receptor (PACAPR) mRNA was expressed at high-levels in AVP-containing neurons in the SON, but at very low-levels in oxytocin-containing neurons. PACAPR-like immunoreactivity was found in SON and it was observed in the post-synaptic membranes as well as on the rough endoplasmic reticulum and cytoplasmic matrices in the magnocellular neurons. Doses of PACAP in the nanomolar range increased cytoplasmic Ca2+ concentrations ([Ca2+]i) in AVP-containing neurons; the increase in [Ca2+]i was inhibited by a protein kinase A blocker. These findings suggest that PACAP serves as a transmitter and/or modulator and the activation of PACAPR stimulates a cAMP-protein kinase A pathway which in turn evokes the Ca2+ signaling system. It is hypothesized that PACAP regulates the functions of AVP-containing neurons which participate in the control of plasma osmolarity and blood pressure.


  •  VUODELTA 2000
Biochem J. 2000 May 1;347 Pt 3:733-40. Persistent activation of Gsalpha through limited proteolysis by calpain.

Source

Department of Molecular Biology, Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan. k-kusu@rinshoken.or.jp

Abstract

Treatment of rat pituitary GH(4)C(1) cell membranes with calpain, a calcium-activated cysteine protease, increased adenylate cyclase activity, and this activity was inhibited by a calpain inhibitor, leupeptin. Calpain treatment potentiated the activity of guanosine 5'-[gamma-thio]triphosphate (GTP[S]), but did not attenuate MnCl(2) action on adenylate cyclase, suggesting that calpain acted at the G-protein level, rather than directly on adenylate cyclase. This calpain stimulation of adenylate cyclase was inhibited by an antibody raised against the C-terminal portion of G(s)alpha, but not by anti-G(i)2alpha or anti-Gbeta antibodies. Furthermore, it was shown that G(s)alpha is more susceptible to calpain-mediated proteolysis than G(i)2alpha or Gbeta. Therefore the stimulatory effect of calpain on adenylate cyclase is due to the cleavage of G(s)alpha in GH(4)C(1) cell membranes. Proteolysis of G(s)alpha by micro-calpain involved sequential cleavages at two sites, resulting in the generation of a 39 kDa fragment first, and then a 20 kDa fragment, from the C-terminus. Treatment of GH(4)C(1) cell membranes with cholera toxin increased the rate of cleavage. Cholera toxin treatment of intact GH(4)C(1) cells induced the translocation of calpain from the cytosol to the membranes, a hallmark of calpain activation. In addition, treatment of intact GH(4)C(1) cells with a calpain-specific inhibitor, benzyloxycarbonyl-Leu-leucinal, blocked the increased cAMP production and the down-regulation of G(s)alpha, which were produced by cholera toxin or pituitary adenylate cyclase-activating polypeptide. These results suggest that calpain sustains adenylate cyclase in an active form through the cleavage of G(s)alpha to an active G(s)alpha fragment. This is a novel calpain-dependent activation mechanism of G(s)alpha and, thus, of adenylate cyclase in rat pituitary cells.
PMID:
10769177
[PubMed - indexed for MEDLINE]

PMCID:
PMC1221010

Free PMC Article
  • VUODELTA 1989
J Biol Chem. 1989 Apr 5;264(10):5352-7. Cholera toxin induces cAMP-independent degradation of Gs.

Source

Department of Pharmacology, University of California, San Francisco 94143.

Abstract

Cholera toxin stimulates adenylyl cyclase by catalyzing ADP-ribosylation of the alpha chain (alpha s) of Gs, a guanine nucleotide binding regulatory protein. In a rat pituitary cell line, GH3, the toxin-induced increase in GTP-dependent adenylyl cyclase activity is maximal at 1 h; adenylyl cyclase remains elevated for at least 32 h. Surprisingly, cholera toxin also induces a 74-95% decrease in the amount of immunoreactive alpha s in the same cells, as assessed on immunoblots probed with either of two antisera directed against separate alpha s peptide sequences. The decrease in immunoreactive alpha s, which begins after 1 h of toxin treatment and is complete by 8 h, is accompanied by a comparable decrease in the amount of biochemically active alpha s, as assessed by its ability to complement the biochemical defect of alpha s-deficient S49 cyc- membranes. Cholera toxin induces similar decreases in alpha s in wild type S49 lymphoma cells, in S49 kin- mutants, which lack cAMP-dependent protein kinase, and in S49 H21 a mutants, in which alpha s is unable to assume an active conformation upon binding GTP. The toxin-induced decrease in alpha s is somewhat temperature-dependent, but is not blocked by agents that increase lysosomal pH or by colchicine, which promotes breakdown of microtubules. alpha s in detergent-solubilized GH3 membranes is susceptible to proteolysis by an endogenous protease; this susceptibility is markedly increased in membranes from cells previously exposed to cholera toxin for 1 h. Taken together, these results suggest that cholera toxin-induced covalent modification of alpha s marks the protein for accelerated degradation. In addition, the persistence of elevated GTP-dependent adenylyl cyclase activity despite loss of a substantial fraction of alpha s suggests that the amount of alpha s membranes is greater than the amount necessary for maximal activation of cAMP synthesis by cholera toxin.
PMID:
2538415
[PubMed - indexed for MEDLINE]
Free full text

onsdag 2 januari 2013

VIBRIO spp., VIBRIONACEAE

Göteborgin Yliopistosta ilmesyi väitöskirja
 Collin Betty. Characterization and persistence of potential human pathogenic vibrios in aquatic environments.  Institute of Biomedicine at Sahlgrenska Academy University of Gothenburg. (7. June 2012) ISBN 978-91-628-8492-6.

Väitöskirjan sisällöstä:
VIBRIO lajit  (Vibrio spp.) ovat  vesimiljöön luonnollista asujaimistoa. ja muuan kaikkein taavllisin syy maailman bakterielleihin gastroenteriitteihin.  Sitä  tulee ihmiseen meriravinnosta, kontaminoituneesta juomavedestä tai altistuksesta merivedelle.
Suurin osa VIBRIO-lajeista on kuitenkin avirulentteja, mutta jotkutkannat  voivat sporadisesti ( satunnaisesti) olla ihmispatogeenejä.
VIBRIO CHOLERAE  saattaa aiheutaa koleraa ja fataaleja haavainfektioita.
VIBRIO PARAHAEMOLYTICUS voi aiheuttaa gastroenteriittiä.
VIBRIO VULNIFICUS  voi aiheuttaa haavainfektioita ja sepsistä, verenmyrkytystä.

Tässä väitöstyössä haluttiin epidemisten ja laboratoriotutkimusten avulla lisätä tietämystä vesissä tavattavien  ihmispatogeenisten VIBRIO-lajien esiintymisestä,  niitten sijoittautumisesta  ekomiljööseen  ja  niiden pinttyneisyydestä ihmisten taudinaiheuttajina.
Tiedemiehet tutkivat VIBRIO-lajien  vuodenaikavariaatiota simpukoissa ja näkinkengissä sekä Mosambikissa että Ruotsissa . He eristivät  ja luonnehtivat havaitsemiansa VIBRIO-kantoja ja vertailivat niitä Intian vesinäytteistä peräisin oleviin kantoihin.

 Mosambikin simpukoista tehtiin  havainto, että VIBRIO-lajeja esiintyi eniten lämpimän sadekauden aikana ja hallitsevin laji oli V.  PARAHAEMOLYTICUS.
Biokemiallisesti  ja PCR- seulonnalla  tehyjen   virulanssin arviointien  perusteella  erilaisista vesimiljöistä peräisin olevat kannat olivat  hyvin suuresti samankaltaisia. Kuitenkin  eroavuuksia esiintyi  eristettyjen kantojen funktionaalisissa hemolyysianalyyseissä ja antibioottiresistenssissä. 

Ruotsalaiset ja intialaiset VIBRIO- kannat olivat epäherkempiä testatuille antibiooteille ja niiden hemolyyttisyys oli heikompaa kuin Mosambikista  eristetyillä kannoilla.
Ruotsalaisista näkinkengistä peräisin olevien VIBRIO-lajien  bakteeri-DNA:n molekulaariset analyysit osoittivat kolmen VIBRIO-lajin ja niiden virulenssigeenien (ctx, tcp, toxR)(tdh, trh) vvh, viuB)  assosioituvan ihmisten tauteihin. Merivesi- ja kliinisistä miljöistä eristetyt kannat olivat  yhtälailla ja suuresti haitallisia testatuille eukaryoottisille soluille.

In vivo tutkimuksilla selvitettiin  kliinisen V. CHOLERAE- bakteerin   pinttynyt esiintyminen vesiympäristöissä.  Kantoja altistettiin näkinkengille, joitten bakteerinottoa ja eliminaatiota sitten tutkittiin.  Näkinkengät  kykenivät välttämään kaikkein vahvimpia VIBRIO-kantoja sulkemalla tiiviisti simpukkaisen kuorensa. Mutta  heikompia VIBRIO-kantoja  kertyi näkinkenkien sisäkudokseen matalin pitoisuuksin ja erästä merivesiperäistä kontrollikantaa   enemmänkin.  Näkinkengät eliminoivat patogeenista kantaa  tehottomammin kuin  meriperäistä kantaa. 

Yksi kliininen VIBRIO- kanta ja yksi meriperäinen kanta. altistettiin sitten 4 Celsiusasteeseen 21 päiväksi ja sitten lämpötilaa nostettiin 20 Celsiusasteeseen.  Kliininen kanta menetti enemmän viljeltävyyttään kuin meriperäinen kanta 4 C   asteessa, mutta kun vettä lämmitettiin, kliinisen kannan viljeltävyyskyky  palautui  merkitsevästi  enemmän kuin meriperäisen kannan. (Vesi on raskainta 4 Celsiusasteessa, joten se on pohjalla).

Sitten tutkijat selvittivät kliinisten kantojen pinttyneisyyttä luonnollisessa  pohjasedimentissä. Inkuboitiin samalla tavalla kuin edellä  ja havaittiin sedimentissa olevien kantojen vähentävän viljeltävyyslukujaan kuten vedessäkin inkuboidut. 
Koska  kliiniset V. CHOLERAE kannat eivät pidä  mukanaan mitään standardisoitua virulenssigeenivalikoimaa, niiden  kyky vaihtua  epäviljeltävästä muodosta (VBNC)  viljelyskelpoiseen  muotoon saattaa olla hyvin tärkeä seikka kannan patogeenisyydessä.

 Tulokset osoittavat myös, että luonnollinen pohjasedimentti saattaa olla ihmispatogeenisten  VIBRIO-lajien mahdollinen reservoaari (säiliö).

TAXONOMIA 
Bergeys Manual of Systematic Bacteriology (Garrity 2005)
Phylum
PROTEOBACTERIA
Class
GAMMAPROTEOBACTERIA
Order
VIBRIONALES
Family
VIBRIONACEAE
Genus
VIBRIO spp. ( over 60 species)
  • human pathogenic strans
V. CHOLERAE, over 200 serogroups;  O1 and O139 pandemic cholera
V.PARAHAEMOLYTICUS, groups according antigens,(2005:)  75 combinations of  O and K antigens identified, 11 belongs to the pandemic clone.
  • non-pathogenic strains

VIBRIOITTEN kliininen merkitys ihmiskunnalle
WHO: Vuosittain sairastuu 3-5 miljoonaa koleraan.
100,000- 200,000 menehtyy koleraan vuosittain.