Differential effect of phosphodiesterase
inhibitors on IL-13 release from
peripheral blood mononuclear cells.
Reference: Clin Exp Immunol 2001;126(3):384-389.
Increased cyclic AMP (cAMP)-phosphodiesterase (PDE) activity in peripheral
blood leucocytes
is associated with the immunological inflammation that characterizes allergic
diseases, such as
atopic dermatitis and allergic rhinitis. Recently, it has been found that
IL-13 has similar biological
functions to IL-4. The aim of this study was to investigate the possible
involvement of
cAMP-PDE activity on IL-13 release from peripheral blood mononuclears cells
(PBMC) from
atopic asthma patients. Phytohaemagglutinin (PHA)-induced IL-13 release
from PBMC was
concentration-dependently inhibited by rolipram, a type 4 PDE inhibitor,
as well as by dibutyryl
cAMP, a membrane-permeant cAMP analogue. However, theophylline, a non-specific
PDE
inhibitor, and cilostazol, a type 3 PDE inhibitor, failed to inhibit IL-13
release. The inhibitory
effect of rolipram was enhanced by the addition of forskolin (10-4 m),
an adenylyl cyclase
stimulator. PHA itself did not alter the intracellular cAMP level. Rolipram
concentration-dependently increased cAMP level in PHA-stimulated PBMC,
and this increase
was synergistically facilitated by the addition of forskolin (10-4 m).
These results suggest that
type 4 PDE inhibitors, alone or synergistically in combination with forskolin,
inhibit PHA-induced
IL-13 release from PBMC of atopic asthma patients by elevating intracellular
cAMP
concentrations. These inhibitors have the potential to exert an anti-inflammatory
effect by
inhibiting IL-13 production in allergic diseases such as atopic asthma.
A New Device for the Measurement of Disease
Severity in Patients with
Intermittent Claudication.
Reference: Eur J Vasc Endovasc Surg 2001;22(6):516-522.
Objectives: to assess a new method of determining functional impairment
in patients with
intermittent claudication, the Double Physiological Walking Test (DPWT)
using the PADHOC
(Peripheral Arterial Disease Holter Control) device, against a standard
treadmill test. Design:
patients with intermittent claudication presenting to the department were
considered for both the
DPWT and a standard treadmill test. Methods: initial claudicating distance,
maximal walking
distance and speed of walking were determined for both parts of the DPWT.
Initial claudicating
distance and maximal walking distance were determined from the treadmill
test. Comparisons
were made between the treadmill test and the DPWT. Results: the treadmill
test was unable to be
performed in 22% of patients due to defined contraindications. There were
strong correlations in
both walking distances and disease severity when comparing the DPWT and
the treadmill test.
Patients in whom the treadmill test was contraindicated had significantly
shorter walking distances
on the DPWT than those who were able to complete a treadmill walking test.
Conclusions: the
DPWT correlates strongly with walking distances obtained from a standard
treadmill test.
However, the PADHOC can be used in a number of differing locations and
settings as well as in
patients in whom a treadmill test is contraindicated. It therefore has
a role to play in the initial
assessment of patients presenting with intermittent claudication.
Synergy between medical and nutrient therapies:
George Washington meets
Rodney Dangerfield.
Reference: J Am Coll Nutr 2001;20(5S):349S-353S.
Although medical therapies are widely accepted by health practitioners,
sometimes without
adequate testing, nutritional therapy is frequently looked upon uniformly
as without merit. There
are many reasons for this attitude. However, a substantial body of literature
has accumulated that
objectively demonstrates the value of adding nutritional therapy to the
prevention or treatment of
some diseases or specific risk factors for diseases. Examples of successful
nutrition therapy that
can be combined with medical management include treatment of hypertension,
hyperlipidemia,
intermittent claudication, osteoporosis, respiratory distress syndrome,
and arthritis.
Management of Painful Diabetic Neuropathy.
Reference: Drugs Aging 2001;18(10):737-749.
Type 2 diabetes mellitus is a prevalent disease in the US which affects
more than 15 million
people. As the disease progresses over time, neuropathic pain can become
a common
complication; it is present in more than 50% of individuals with diabetes
mellitus aged >60 years.
The pathogenesis of diabetic neuropathy is theorised to be multifactorial.
Numerous medications,
some with different mechanisms of action, have been examined regarding
their effects on the
symptoms associated with diabetic neuropathy such as pain, paraesthesia
and numbness.
However, the majority of the studies have included small patient populations.
Tricyclic
antidepressants, amitriptyline and desipramine in particular, have been
relatively well studied and
shown to be effective. However, anticholinergic adverse effects may limit
their usefulness and
may preclude use in the elderly. Studies have also shown gabapentin to
be effective and well
tolerated in the treatment of diabetic neuropathy. Capsaicin cream provides
another treatment
option with a favourable adverse effect profile. Many other medications
have been evaluated in
diabetic neuropathy; however, more placebo-controlled studies with adequate
patient
populations need to be performed to solidify their role in treatment. |
Volume
5, Number 1: January 2002
