Thank you, it's cool. Used for the first time because only then was the right drug. Very revealing detail: ordered Express shipping to get the order within 3 hours because didn't know how to get the order faster https://africarx.co.za/buy-cialis-south-africa.html The drug is authentic exactly. Consistent with the stated prices the Staff is knowledgeable.
Layout
Obesity is now a major concern in the Western world, as it can lead to health problems
such as diabetes, cardiovascular disease, hypertension and some forms of cancer. Here,
Richard A Collins looks at the efficacy of hydroxycitric acid, one of the components in
various over-the-counter weight-loss formulations and appetite-suppressor products. Hydroxycitric acid and weight loss Losing weight has become a modern-day obsession. Regardless of the personal
‘Obesity and overweight are factors that
reasons for wanting to lose weight, there is certainly a need for wider concern about obesity and being overweight. A person whose body mass index (BMI) is greater than 25 kg/m2 is defined as overweight, and over 30 kg/m2 is regarded as obese. Globally, there are more than one billion overweight adults,1 of whom at least 300 million are obese.
the healthcare system.2 Obesity places an
some areas and is on the rise in others.
induce weight loss are illegal (amphetamines),
Worldwide, about 22 million children under
service, with the direct costs being at least
dangerous (fenfluramine, ephedra), addictive
five years of age are overweight. Obesity and
£500 million per year.3 The cost of obesity-
related healthcare varies with the degree
(opioid antagonists, amylin) or are indicated
diseases and disability, including type 2
of obesity. Overall, the healthcare costs for
for other conditions (fluoxetine [Prozac] –
diabetes, cardiovascular disease, hypertension
an antidepressant). Few detailed studies on
and stroke, and certain forms of cancer.
double those of a person of normal weight.4
the safety or efficacy of other potentially
contribute to the increase in the number
induce weight loss and it is impossible to
of overweight and obese individuals. Busy
vast number of dietary regimes introduced
laevorotatory optical isomer (L-hydroxycitric
healthy meals or participating in regular
over the decades. For those unable to stick
acid or [-]-hydroxycitric acid) of which has
exercise or sporting activities. Energy-dense
food high in saturated fats and sugars are
treatment of obesity, government agencies
Hydroxycitric acid
have suggested that the direct and indirect
which help regulate the sense of fullness,
Hydroxycitric acid is purported to be one of
costs associated with obesity may overwhelm
and this results in reduced food intake.
the active components in various over-the-
gastrointestinal lipases. It acts in the lumen
forming a covalent bond with the activeserine residue sites of gastric and
pancreatic lipases. Thus, the inactivatedenzymes are unavailable to hydrolyse
dietary fat (ie triglycerides) into absorbablefree fatty acids and monoglycerides, which
control. Systemic absorption of the drug is not needed for activity. At the
Fig 1. Chemical structure of
three times a day), orlistat inhibits dietary
THE BIOMEDICAL SCIENTIST September 2006
counter weight-loss formulations andappetite-suppressor products. It is obtained
Fig 2. Garcinia cambogia, is
from the rind of the fruit of Garciniacambogia (also known as brindal berry,
the rind by extraction into water at room
temperature. The crude extract is loaded on
an anion exchange to adsorb HCA, which is
eluted with sodium/potassium hydroxide.
This fraction is then passed through a cation
G. quaesita, G. zeylanica or
exchange column to obtain the free acid.
biologically active form. However, the acid
sodium or calcium salts of HCA. The calcium
sparingly soluble in water and are not well
In a recent study, the peak plasma level of
hydroxycitrate was 8.4 µg/mL two hours after
the oral administration of 2 g G. cambogia
extract to normal subjects.6 Hydroxycitric
acid can be broken down by bile acids and
fats in the intestine and can bind to fibre,pectin and other substances in the diet orsecreted during digestion.
Hydroxycitric acid is an extremely popular
dietary supplement. Between March 2000and September 2003, 225 tonnes of HCA,
Proposed actions
Acetyl-CoA is the basic building block of
G. cambogia and G. cambogia extract were
fatty acids. It is produced by oxidation of
glucose obtained from carbohydrates in the
weight loss, including inhibition of fatty acid
diet via the tricarboxylic acid (TCA) cycle or
by oxidation of fatty acids. Both activities take
place in the mitochondria and cytoplasmic
acetyl-CoA is ultimately derived from citrate
The recommended daily dose of G. cambogiaInhibiting fatty acid synthesis
exported across the mitochondrial membrane
Hydroxycitric acid is a potent competitive,
reversible inhibitor of ATP-citrate lyase
Inhibiting production of acetyl-CoA would
(also known as ATP citrate synthase, citrate
also be expected to deplete the concentrations
regulated by the Dietary Supplement Health
cleavage enzyme) in vitro, and an inhibitor
of subsequent metabolites in the fatty acid
and Education Act in the USA. For dietary
of fatty acid synthesis in rat liver in vivo.10,11
synthetic pathway. The second metabolite
supplements marketed before October 1994,
in the pathway, formed from acetyl-CoA, is
no proof of safety is required for them to
required for the synthesis of fatty acids and
catalyses the following reaction: citrate +
enzyme carnitine acyltransferase, which is
CoA + ATP ➞ oxaloacetate + acetyl-CoA +
needed for the oxidation of fat. Therefore, it is
include contraindications for using HCA in
proposed that reducing malonyl-CoA formation
persons with diabetes, Alzheimer’s disease
with HCA might stimulate fat metabolism.
or dementia or in those who are pregnant or
lactating. Potential drug interactions include
gain and that inhibiting fat synthesis is the
likely mechanism for the observed effect.
β-adrenoreceptor blockers, potentiation of
For example, male rats (n=24) had restricted
access to food (10 g/day) for 10 days followed
hypokalaemia, and risk of arrhythmia when
by ad libitum energy-rich diet for the next
combined with depolarising muscle relaxants
10 days. Half of the rats were supplemented
Studies failed to demonstrate any changes
body weight regain after substantial body
in hepatic and testicular peroxidation, DNA
weight loss; an effect the authors presumed
fragmentation, histopathological changes,
to be due to the inhibiting effect of HCA
haematology or clinical chemistry in rats
on lipogenesis.12 In human studies, however,
whose feed was supplemented with 5% (w/w)
THE BIOMEDICAL SCIENTIST September 2006 Fig 3. Simplified Appetite suppression
Regulation of appetite is a complex process
that is not fully understood. It consists of
involves the integration by the brain of a
variety of signals from peripheral organstransmitted by neurotransmitters, peptides,hormones and metabolites.14 Most anorecticdrugs act by central mechanisms and havemany disadvantages that include limited
expression of serotonin receptor genes in
days and performed endurance exercise.
effectiveness, side effects on the central
abdominal fat tissues of rats fed low-dose
Blood free fatty acid concentrations increased
significantly and the respiratory exchange
ratio (ratio of the amount of carbon dioxide
hyperphagia (over-eating) on discontinuation
ingestion, suggesting that short-term HCA
been tested in animals that act by peripheral
Thermogenesis
ingestion increases fat oxidation in untrained
Thermogenesis is the metabolism of fat or
other compounds to produce heat rather than
that peripherally acting anorectic drugs
metabolic energy in the form of ATP. Evidence from trials
may provide new therapeutic approaches to
Thermogenesis occurs in specialised fatty
It is generally accepted that evidence of
disorders of appetite regulation in humans.
tissue known as brown adipose tissue (brown
efficacy for pharmacological interventions is
A patent for the use of HCA as an appetite
fat). However, it is unclear how HCA exerts
suppressant and an inducer of weight loss
double-blind, placebo-controlled trial. The
fact that such trials have been performed
validated and detailed metabolic studies on
indicated that HCA decreased food intake and
this interesting hypothesis have not been
such frequency and at such high doses for
body weight gain. Body lipid levels decreased
a condition that may lead to serious adverse
but body protein levels remained unchanged.
In contrast, citrate had no such effect.16 In
genetically obese Zucker rats, administration
of HCA in the diet for 39 days reduced food
significantly by short-term administration of
mg HCA per day (n=66) or placebo (n=69)
intake and body weight but had no effect on
for 12 weeks.28 In addition, both groups were
prescribed a high-fibre, low-energy diet.
decreased (P<0.05) during exercise.25 Similar
About two-thirds of subjects in each group
results were obtained in six untrained women
completed the trial. Subjects in each group
taking placebo on weight loss and appetite
lost a significant amount of weight during
suppression. Both groups lost weight, with
The effects of HCA on fat oxidation during
the 12-week treatment period (P<0.001);
moderately intensity exercise in untrained
greater reduction (3.7± 3.1 kg vs 2.4 ±
differences were not statistically significant
2.9 kg). However, there was no difference
ingested 500 mg HCA or a placebo for five
(mean ± SD: 3.2 ± 3.3 kg vs 4.1 ± 3.9 kg;
in appetite variables and the study did not
support a satiety effect of HCA.18 The lack
of effect of HCA on satiety was supported
estimated percentage of body fat mass loss
in a separate trial on 11 overweight males
between treatment groups, and the fraction
of weight loss as fat was not influenced by
the treatment group. The authors concluded
unaffected in 24 adults receiving 900 mg/day
that G. cambogia failed to produce significant
weight loss and fat mass loss beyond that
while 24-hour energy intake was decreased
placebo-controlled trial in 60 moderately
serotonin after feeding are implicated in
conducted in which HCA (2.8 g/day in three
equal doses, given 30–60 minutes before
THE BIOMEDICAL SCIENTIST September 2006
variables. Physiol Behav 2000; 71: 87–94.
BMI decreased by 5–6% in the HCA group.
Saris WH. The effects of 2-week ingestion
Food intake, total cholesterol, low-density
of (-)-hydroxycitrate and (-)-hydroxycitrate
lipoprotein, triglyceride and serum leptin
levels were reduced significantly following
density lipoproteins and excretion of urinary
Int J Obes Relat Metab Disord 2001;
25: 1087–94.
A marginal or non-significant effect was
20 Kovacs EM, Westerterp-Plantenga MS, de
seen in all parameters in the placebo group.29
Vries M et al. Effects of 2-week ingestion
Similar weight loss and beneficial effects on
of (-)-hydroxycitrate and (-)-hydroxycitrate
blood profiles were observed in studies of
82 obese subjects (BMI 30–50.8 kg/m2).23
National Cancer Institute. Garcinia
triglycerides on satiety and food intake. cambogia extract 900045-23-1. Physiol Behav 2001; 74: 543–9. Conclusions
21 Westerterp-Plantenga MS, Kovacs EM.
The effect of (-)-hydroxycitrate on energy
inhibitory effects on the enzyme primarily
intake and satiety in overweight humans.
responsible for fatty acid synthesis in vitro. Int J Obes Relat Metab Disord 2002; 26:
Shara M, Ohia SE, Yasmin T et al. Dose-
demonstrated in in vivo studies in both
22 Roy S, Rink C, Khanna S et al. Body
profile in response to a novel hydroxycitric
acid-based dietary supplement. Gene Expr
The rationale for taking HCA alone in order
2004; 11: 251–62.
to reduce weight is flawed. First, energy
90 days. Mol Cell Biochem 2003; 254:
23 Preuss HG, Garis RI, Bramble JD et al.
Efficacy of a novel calcium/potassium salt
would not disappear simply because it could
Shara M, Ohia SE, Schmidt RE et al.
of (-)-hydroxycitric acid in weight control. Int J Clin Pharmacol Res 2005; 25:
(-)-hydroxycitric acid extract and its effect
24 Wheeler TJ. Hydroxycitrate as a weight-loss ingredient. www.quackwatch.org/
The only sure way of losing excess weight
over a period of 90 days. Mol Cell
25 Lim K, Ryu S, Ohishi Y et al. Short-term
Biochem 2004; 260: 171–86.
(-)-hydroxycitrate ingestion increases fat
oxidation during exercise in athletes. J
exercise. The magic potion that allows food
Arch Biochem Biophys 1969; 135: 200. Nutr Sci Vitaminol (Tokyo) 2002; 48:
11 Lowenstein JM. Effect of (-)-hydroxycitrate
on fatty acid synthesis by rat liver in vivo.
26 Lim K, Ryu S, Nho HS et al. J Biol Chem 1971; 246: 629–32.
(-)-hydroxycitric acid ingestion increases
12 Leonhardt M, Hrupka B, Langhans W.
fat utilization during exercise in untrained
women. J Nutr Sci Vitaminol (Tokyo).
2003; 49: 163–7. Obesity and overweight. www.who.int/
restrictive feeding in male rats. Physiol
27 Tomita K, Okuhara Y, Shigematsu N et al. Behav 2001; 74: 191–6.
(-)-hydroxycitrate ingestion increases fat
obesity/en/ (accessed 22 June 2006).
13 van Loon LJ, van Rooijen JJ, Niesen B
et al. Effects of acute (-)-hydroxycitrate
strategies for the treatment of obesity. Biotechnol Biochem 2003; 67: Curr Drug Targets CNS Neurol Disord
2004; 3: 341–56. Am J Clin Nutr 2000; 72: 1445–50.
28 Heymsfield SB, Allison DB, Vasselli JR
National Audit Office. Tackling obesity inet al. Garcinia cambogia (hydroxycitric
England. Report by the Comptroller and
appetite modulation by drugs. Fed Proc
acid) as a potential antiobesity agent: a
1985; 44: 139–44.
randomized controlled trial. JAMA 1998;
15 Majeed M, Badmaev V, Rajendran R. 280: 1596–600.
29 Preuss HG, Bagchi D, Bagchi M et al. Obes Res 2004; 12: 1936–43.
16 Sullivan C, Triscari J. Metabolic regulation
as a control for lipid disorders. I. Influence
on weight loss. Diabetes Obes Metab
patient. Clin Endocrinol Metab 1976;
2004; 6: 171–80. 5: 455–79.
induced obesity in the rodent. Am J Clin
Loe YC, Bergeron N, Rodriguez N et al. Nutr 1977; 30: 767–76. et al. Effect of (-)-hydroxycitrate on
concentration. Anal Biochem 2001;
292: 148–54.
obese rat. Am J Physiol 1981; 240: E72–8. THE BIOMEDICAL SCIENTIST September 2006
IN THE HIGH COURT OF NAMIBIA THE STATE FRIENDA HAIMANN MUHEKENI HIGH COURT SPECIAL REVIEW CASE NO. 592/08 REVIEW JUDGMENT ANGULA, A.J.: This matter came before me for special review. The letter by the Magistrate under cover of which the records of the “ Due to the continuous misunderstandings between the presiding officer a`nd Mr Hennie Barnard (the Magistrate) I did
How do boys and girls differ in their use of ICT? How do boys and girls differ in their use of ICT? Becta | How do boys and girls differ in their use of ICT? Contents Becta | How do boys and girls differ in their use of ICT? Introduction This briefing explores the differences between boys’ and girls’ use of ICT, both within and outside school, and for both educational and