Procedures for assessing self-administration of' i.v. cocaine have
been reported by Fischman and Schuster (1982) with experienced
cocaine users prepared with two indwelling Angiocath Teflon
catheters, one for drug infusion and one for blood withdrawal.
Subjects were instructed that each of two buttons would be
associated with the same solution (drug or saline) throughout the
study. On the first day, subjects were exposed to each solution and
for the next 8 days were required to press the response button 10
times in order to receive an injection. Once a single response was
made on a given button, the other one was deactivated. A total of
10 injections could be taken during a l-hour session with blood
drawn prior to and after each injection followed by completion of
the POMS and ARC1 questionnaires. After initial sampling on the
first day, subjects consistently chose cocaine over saline.
Subjective ratings of drug effect correlated with the self-injection
of cocaine. The most pronounced effects on subjective states, blood
pressure, heart rate, and cocaine levels occurred after this initial
injection.
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Monday, February 26, 2007
CNS Stimulant Physical Dependence Potential a. Tolerance to Drug Effects
The assessment of tolerance to the effects of the CNS stimulants has
been directed mainly at two of their pharmacologic effects:
anorexia and mood elevation. Tolerance to the appetite-suppressant
effects has been demonstrated to occur in numerous studies. It
appears; however, that obesity has many complex components, at least
one of which, the 'craving" for food, may interact with the
evaluation of tolerance effects (Wooley and Wooley 1981).
The currently accepted criterion for the appetite suppressant effect
is that weight is lost and not recovered. The fact that the rate of
weight loss rapidly decreases over the course of treatment is taken
as evidence of tolerance. Stunkard (1979) has suggested that these
criteria are not valid for assessing tolerance, since a deceleration
in weight loss is common even in more drastic treatments of obesity
such as jejunoileal bypass surgery. Additionally, the metabolic
characteristics of the body change as a result of weight loss, and
these changes should be taken into account when assessing tolerance.
Food that has been ingested during a period of weight loss is more
efficiently metabolized than when the caloric balance is in steady
state (Keesey et al. 1976). A more appropriate determinant of
whether tolerance has developed or not may be the degree of weight
gain following cessation of drug treatment. Tolerance would be
shown by a return to normal weight despite continued administration
of the drug. Rebound hyperphagia and weight gain, upon withdrawal
of the drug, would constitute a withdrawal reaction.
Tolerance to the mood elevating effects of CNS stimulants has been
assessed and, in addition,
effects (Gunne 1977).
is distinct, from the appetite-suppressant
Tolerance to the euphoric effects of
amphetamine (as measured by a subjective questionnaire) was found to
develop rather quickly over 14 days of daily treatment (Rosenberg et
al. 1963). In addition, these authors demonstrated that there was
no cross-tolerance to LSD. To date, no studies have been conducted
to directly compare the degree of tolerance development to the
subjective effects of CNS stimulants.
been directed mainly at two of their pharmacologic effects:
anorexia and mood elevation. Tolerance to the appetite-suppressant
effects has been demonstrated to occur in numerous studies. It
appears; however, that obesity has many complex components, at least
one of which, the 'craving" for food, may interact with the
evaluation of tolerance effects (Wooley and Wooley 1981).
The currently accepted criterion for the appetite suppressant effect
is that weight is lost and not recovered. The fact that the rate of
weight loss rapidly decreases over the course of treatment is taken
as evidence of tolerance. Stunkard (1979) has suggested that these
criteria are not valid for assessing tolerance, since a deceleration
in weight loss is common even in more drastic treatments of obesity
such as jejunoileal bypass surgery. Additionally, the metabolic
characteristics of the body change as a result of weight loss, and
these changes should be taken into account when assessing tolerance.
Food that has been ingested during a period of weight loss is more
efficiently metabolized than when the caloric balance is in steady
state (Keesey et al. 1976). A more appropriate determinant of
whether tolerance has developed or not may be the degree of weight
gain following cessation of drug treatment. Tolerance would be
shown by a return to normal weight despite continued administration
of the drug. Rebound hyperphagia and weight gain, upon withdrawal
of the drug, would constitute a withdrawal reaction.
Tolerance to the mood elevating effects of CNS stimulants has been
assessed and, in addition,
effects (Gunne 1977).
is distinct, from the appetite-suppressant
Tolerance to the euphoric effects of
amphetamine (as measured by a subjective questionnaire) was found to
develop rather quickly over 14 days of daily treatment (Rosenberg et
al. 1963). In addition, these authors demonstrated that there was
no cross-tolerance to LSD. To date, no studies have been conducted
to directly compare the degree of tolerance development to the
subjective effects of CNS stimulants.
Appetite
Procedures for assessing the effects of stimulants on appetite have
been developed for short-term, single dose experiments. Hoebel et
al. (1975) utilized a procedure that tests a drug's effectiveness in
reducing intake of a diet liquid meal product. Volunteers report to
the laboratory having refrained from eating for 2 hours prior to
lunchtime (12 noon). Using a double-blind cross-over design,
subjects were given either placebo or 25 mg of phenylpropanolamine
30 minutes before lunch. Lunch consisted of a canned chocolateflavored
drink which was dispensed via a long straw from a graduated
cylinder. The reservoir was hidden from the subject's view.
Subjects were instructed to drink as much as they wished.. Upon
completion of lunch they filled out questionnaires that related to
the taste of the lunch, the reason for stopping, the amount that
they consumed relative to the previous day, and the taste of the
lunch relative to the previous day.
been developed for short-term, single dose experiments. Hoebel et
al. (1975) utilized a procedure that tests a drug's effectiveness in
reducing intake of a diet liquid meal product. Volunteers report to
the laboratory having refrained from eating for 2 hours prior to
lunchtime (12 noon). Using a double-blind cross-over design,
subjects were given either placebo or 25 mg of phenylpropanolamine
30 minutes before lunch. Lunch consisted of a canned chocolateflavored
drink which was dispensed via a long straw from a graduated
cylinder. The reservoir was hidden from the subject's view.
Subjects were instructed to drink as much as they wished.. Upon
completion of lunch they filled out questionnaires that related to
the taste of the lunch, the reason for stopping, the amount that
they consumed relative to the previous day, and the taste of the
lunch relative to the previous day.
Electroencephalographic (EEG) Activity and Sleep
The direct effects of CNS stimulants on EEG activity have been shown
to be alerting or activating as determined by the qualitative
techniques of visual inspection. The desynchronized pattern of EEG
activity, characterized by a slight decrease in amplitude and an
increase in predominant frequency, has been quantified by the use of
voltage integration procedures (Goldstein et al. 1963). Although
the use of power spectral analysis has not been employed extensively
to assess the EEG effects of this class of compounds, a report by
Gibbs and Maltby (1943) did describe a shift in the spectrum to
higher frequencies following benzedrine.
to be alerting or activating as determined by the qualitative
techniques of visual inspection. The desynchronized pattern of EEG
activity, characterized by a slight decrease in amplitude and an
increase in predominant frequency, has been quantified by the use of
voltage integration procedures (Goldstein et al. 1963). Although
the use of power spectral analysis has not been employed extensively
to assess the EEG effects of this class of compounds, a report by
Gibbs and Maltby (1943) did describe a shift in the spectrum to
higher frequencies following benzedrine.
Candida albicans
Inositol is considered a growth factor in yeast cells and it plays an important role in Candida as
an essential precursor for phospholipomannan, a glycophosphatidylinositol (GPI)-anchored
glycolipid on the cell surface of Candida which is involved in the pathogenicity of this opportunistic
fungus and which binds to and stimulates human macrophages. In addition, inositol plays an
essential role in the phosphatidylinositol signal transduction pathway, which controls many cell
cycle events. Here, high-affinity myo-inositol uptake in Candida albicans has been characterized,
with an apparent Km value of 240±15 mM, which appears to be active and energy-dependent
as revealed by inhibition with azide and protonophores (FCCP, dinitrophenol). Candida
myo-inositol transport was sodium-independent but proton-coupled with an apparent Km value of
11?0±1?1 nM for H+, equal pH 7?96±0?05, suggesting that the C. albicans myo-inositol–H+
transporter is fully activated at physiological pH. C. albicans inositol transport was not affected by
cytochalasin B, phloretin or phlorizin, an inhibitor of mammalian sodium-dependent inositol
transport. Furthermore, myo-inositol transport showed high substrate specificity for inositol and
was not significantly affected by hexose or pentose sugars as competitors, despite their structural
similarity. Transport kinetics in the presence of eight different inositol isomers as competitors
revealed that proton bonds between the C-2, C-3 and C-4 hydroxyl groups of myo-inositol and the
transporter protein play a critical role for substrate recognition and binding. It is concluded that
C. albicans myo-inositol–H+ transport differs kinetically and pharmacologically from the human
sodium-dependent myo-inositol transport system and constitutes an attractive target for delivery of
cytotoxic inositol analogues in this pathogenic fungus.
The yeast Candida albicans is one of the most commonly
encountered human pathogens and is a normal component
of the human endogenous microflora. As an important
nosocomial and opportunistic fungus, C. albicans can cause
a wide variety of infections ranging from mucosal infections
in generally healthy persons to life-threatening
systemic infections in individuals with impaired immune
defence, cancer therapy, antibiotic treatment, diabetes or
burn victims. Furthermore, the development of drug
resistance and the limitations and severe side effects of
drug treatment pose an increasing problem with regard to
C. albicans infections (Vanden Bossche et al., 1998; Pfaller
et al., 1998; Cowen et al., 2002).
Inositol is considered a growth factor in yeast cells and
necessary for their optimum growth (Nikawa et al., 1982,
1991), despite the ability of some yeasts, including Saccharomyces
cerevisiae, to also synthesize myo-inositol de novo
at the expense of glycolysis. Inositol plays an important
role in Candida as an essential precursor for phospholipomannan,
a family of glycophosphatidylinositol (GPI)-
anchored glycolipids on the cell surface of Candida that
is involved in the pathogenicity of this fungus and which
binds to and stimulates human macrophages (Trinel et al.,
1999). Thus, phospholipomannan is considered a virulence
factor in Candida and has been shown to possess immunomodulatory
properties such as TNF-a induction (Jouault
et al., 1994). GPI-membrane anchors are of particular
significance in lower eukaryotes and parasitic protozoa
(McConville & Ferguson, 1993), and about 60 GPIanchored
membrane proteins were estimated in yeast from
the Saccharomyces cerevisiae genome project (Su¨tterlin et al.,
1997). Moreover, inhibition of GPI-anchor biosynthesis was
shown to be lethal in Saccharomyces cerevisiae (Leidich et al.,
1994). In addition to its role as an essential precursor for
GPI-membrane anchors, inositol plays a central role also
in the phosphatidylinositol signal transduction pathway,
which controls many cell cycle events in eukaryotic cells.
Hence, myo-inositol transport in C. albicans appears to
be an attractive drug target to interfere with important
Abbreviations: FCCP, carbonylcyanide-4-(trifluoromethoxy) phenylhydrazone;
GPI, glycophosphatidylinositol.
an essential precursor for phospholipomannan, a glycophosphatidylinositol (GPI)-anchored
glycolipid on the cell surface of Candida which is involved in the pathogenicity of this opportunistic
fungus and which binds to and stimulates human macrophages. In addition, inositol plays an
essential role in the phosphatidylinositol signal transduction pathway, which controls many cell
cycle events. Here, high-affinity myo-inositol uptake in Candida albicans has been characterized,
with an apparent Km value of 240±15 mM, which appears to be active and energy-dependent
as revealed by inhibition with azide and protonophores (FCCP, dinitrophenol). Candida
myo-inositol transport was sodium-independent but proton-coupled with an apparent Km value of
11?0±1?1 nM for H+, equal pH 7?96±0?05, suggesting that the C. albicans myo-inositol–H+
transporter is fully activated at physiological pH. C. albicans inositol transport was not affected by
cytochalasin B, phloretin or phlorizin, an inhibitor of mammalian sodium-dependent inositol
transport. Furthermore, myo-inositol transport showed high substrate specificity for inositol and
was not significantly affected by hexose or pentose sugars as competitors, despite their structural
similarity. Transport kinetics in the presence of eight different inositol isomers as competitors
revealed that proton bonds between the C-2, C-3 and C-4 hydroxyl groups of myo-inositol and the
transporter protein play a critical role for substrate recognition and binding. It is concluded that
C. albicans myo-inositol–H+ transport differs kinetically and pharmacologically from the human
sodium-dependent myo-inositol transport system and constitutes an attractive target for delivery of
cytotoxic inositol analogues in this pathogenic fungus.
The yeast Candida albicans is one of the most commonly
encountered human pathogens and is a normal component
of the human endogenous microflora. As an important
nosocomial and opportunistic fungus, C. albicans can cause
a wide variety of infections ranging from mucosal infections
in generally healthy persons to life-threatening
systemic infections in individuals with impaired immune
defence, cancer therapy, antibiotic treatment, diabetes or
burn victims. Furthermore, the development of drug
resistance and the limitations and severe side effects of
drug treatment pose an increasing problem with regard to
C. albicans infections (Vanden Bossche et al., 1998; Pfaller
et al., 1998; Cowen et al., 2002).
Inositol is considered a growth factor in yeast cells and
necessary for their optimum growth (Nikawa et al., 1982,
1991), despite the ability of some yeasts, including Saccharomyces
cerevisiae, to also synthesize myo-inositol de novo
at the expense of glycolysis. Inositol plays an important
role in Candida as an essential precursor for phospholipomannan,
a family of glycophosphatidylinositol (GPI)-
anchored glycolipids on the cell surface of Candida that
is involved in the pathogenicity of this fungus and which
binds to and stimulates human macrophages (Trinel et al.,
1999). Thus, phospholipomannan is considered a virulence
factor in Candida and has been shown to possess immunomodulatory
properties such as TNF-a induction (Jouault
et al., 1994). GPI-membrane anchors are of particular
significance in lower eukaryotes and parasitic protozoa
(McConville & Ferguson, 1993), and about 60 GPIanchored
membrane proteins were estimated in yeast from
the Saccharomyces cerevisiae genome project (Su¨tterlin et al.,
1997). Moreover, inhibition of GPI-anchor biosynthesis was
shown to be lethal in Saccharomyces cerevisiae (Leidich et al.,
1994). In addition to its role as an essential precursor for
GPI-membrane anchors, inositol plays a central role also
in the phosphatidylinositol signal transduction pathway,
which controls many cell cycle events in eukaryotic cells.
Hence, myo-inositol transport in C. albicans appears to
be an attractive drug target to interfere with important
Abbreviations: FCCP, carbonylcyanide-4-(trifluoromethoxy) phenylhydrazone;
GPI, glycophosphatidylinositol.
Friday, February 23, 2007
Advantage Processors
The Advantage Processors is A Merchant account is an account at a financial institution that allows you to accept credit cards. You may find that you can acquire a Merchant account directly from your local bank or you may decide to use any of a number of Merchant account Providers that can be found using your favorite search engine. Not all Merchant Accounts can connect to the Internet, and the ones that can may be limited to a particular Secure Payment Gateway, so be sure to determine how this account will connect to your site if you are a web Merchant. A Merchant account Provider will open an account at a financial institution (a bank they are partnered with) for you that can handle Internet transactions. Be aware that there are a lot of non-reputable Merchant account Providers out there, so make sure you check them out before you commit to one. Avoid all the hype and jargon, and don't pay more than a $100 processing fee to get the account. Providers can get you equipment and software to process credit cards, however you don't necessarily have to buy the equipment or software from them if you feel their prices aren't within your budget range. All Merchant accounts will have some kind of set up or application fee, which is usually at least $99. In cases where there is no fee, they are making up the difference with software or equipment sales, or otherwise marking up the transaction charges to cover this cost.The process a transaction goes through is actually quite complicated, however it only takes a few seconds. Here's an inside look at how credit card transactions are processed using an Internet credit card processing solution:
1. The customer elects to move to the check out with the items they placed into their shopping cart or selected from the order form on a Merchant's Website.
http://www.advantageprocessors.com/
2. The customer then selects "credit card" as their method of payment.
3. Their browser connects to the Website host's secure server, and brings up the secure payment form.
4. The customer enters in his or her credit card information on the secure payment form, and authorizes the transaction by clicking a "Complete Order" type button.
5. The transaction information flows to the Website host's secure server using SSL encryption.
6. The secure server connects to the Merchant's processing bank either via a Secure Payment Gateway (a third party who provides the connection to the processing bank via land line), or directly (some processors have their own proprietary Secure Payment Gateway and therefore do not require a third party to provide this service).
7. The processor polls the card network, such as Visa® or MasterCard®, directly, and the validity of the card, and availability of funds is confirmed.8. If the transaction's approved, an authorization code is returned to the processor, or to the Secure Payment Gateway from the processor.
9. The authorization is encrypted by the Payment Gateway or processor and transmitted in encrypted form to the Web server of the Merchant , which triggers fulfillment of the order.
10. The Merchant's Web server then sends the customer's browser a confirmation receipt.
11. The amount due is moved from the card holder's bank to the Merchant 's processing bank. The Merchant's processing bank will then move the money to the Merchant 's local bank within 2 to 3 business days.
1. The customer elects to move to the check out with the items they placed into their shopping cart or selected from the order form on a Merchant's Website.
http://www.advantageprocessors.com/
2. The customer then selects "credit card" as their method of payment.
3. Their browser connects to the Website host's secure server, and brings up the secure payment form.
4. The customer enters in his or her credit card information on the secure payment form, and authorizes the transaction by clicking a "Complete Order" type button.
5. The transaction information flows to the Website host's secure server using SSL encryption.
6. The secure server connects to the Merchant's processing bank either via a Secure Payment Gateway (a third party who provides the connection to the processing bank via land line), or directly (some processors have their own proprietary Secure Payment Gateway and therefore do not require a third party to provide this service).
7. The processor polls the card network, such as Visa® or MasterCard®, directly, and the validity of the card, and availability of funds is confirmed.8. If the transaction's approved, an authorization code is returned to the processor, or to the Secure Payment Gateway from the processor.
9. The authorization is encrypted by the Payment Gateway or processor and transmitted in encrypted form to the Web server of the Merchant , which triggers fulfillment of the order.
10. The Merchant's Web server then sends the customer's browser a confirmation receipt.
11. The amount due is moved from the card holder's bank to the Merchant 's processing bank. The Merchant's processing bank will then move the money to the Merchant 's local bank within 2 to 3 business days.
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this is the exlint site provide tool for sell or bye your advertise for your blogs
this is an internet advertising also for marketing service connecting buyers of ad space and publishers of websites with one another in a fast and easy to use method. Publishers can set their own pricing per week, per month or at per click rates.
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Thursday, February 22, 2007
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