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Aqueous humour and serum zinc and copper
concentrations of patients with glaucoma and cataract
Akyol N.; Deger O.; Keha E.E.; Kilic S.
Dept of Ophthalmology, Faculty of Medicine, Karadeniz Tech
University,61080 Trabzon Turkey
British Journal of Ophthalmology (United Kingdom) 1990, 74/11
(661-662)
Serum and aqueous humour zinc and copper concentrations of
44 patients with glaucoma and cataract were determined. Serum
values were found within normal ranges. The highest mean
copper concentration was seen in the glaucoma group. In
addition there was a significant negative correlation between
the aqueous humour levels of zinc and copper in patients with
glaucoma. It was concluded that an increased copper value
together with a low zinc value might be of importance in
patients with glaucoma.
Analysis of the medical use of marijuana and its
societal implications
Taylor HG
Sparrow Hospital, Lansing, Michigan 48826, USA
hgtaylor@pilot.msu.edu
J Am Pharm Assoc (Wash) (U S) Mar-Apr 1998, 38 (2)
p220-7
OBJECTIVE: To review the pharmacology, therapeutics,
adverse effects, and societal implications of the medical use
of marijuana.
DATA SOURCES: MEDLINE and manual searches of
English-language marijuana literature, supplemented with
interviews of scientists currently conducting cannabinoid
research. Search terms included pain OR palliative care AND
cannabis or ALL marijuana; cachexia OR appetite OR appetite
stimulants; muscle spasticity OR spasm; immune system and
cannabis; nausea and vomiting and cancer and cannabis. MEDLINE
search terms: cannabis OR marijuana smoking OR marijuana
abuse; all glaucoma ; multiple sclerosis AND cannabis OR
marijuana smoking OR marijuana abuse.
STUDY SELECTION: Studies on pharmacology, risks, and
medical potential of marijuana.
DATA EXTRACTION: Not applicable.
DATA SYNTHESIS: The most prominent effects of marijuana are
mediated by receptors in the brain. Acute intoxication is
characterized by euphoria, loss of short-term memory,
stimulation of the senses, and impaired linear thinking.
Depersonalization and panic attacks are adverse effects.
Increased heart rate and reddened conjunctivae are common
physical effects. Chronic, high doses may cause subtle
impairment of cognitive abilities that are appear to be
long-term, but of unknown duration. Marijuana may be a risk
factor for individuals with underlying mental illness. It
causes dependence, but compared with cocaine, alcohol, heroin,
and nicotine, marijuana has little addictive power and
produces only mild withdrawal symptoms. Marijuana shows
clinical promise for glaucoma, nausea and vomiting, analgesia,
spasticity, multiple sclerosis, and AIDS wasting syndrome.
CONCLUSION: As a recreational drug, marijuana poses
dangers, particularly to social and emotional development
during adolescence and young adulthood. As a medical drug,
marijuana should be available for patients who do not
adequately respond to currently available therapies. (57
Refs.)
Glycerol: Biochemistry, pharmacokinetics and
clinical and practical applications
Robergs R.A.; Griffin S.E.
Dr. R.A. Robergs, Ctr. Exercise Applied Human Physiol.,
Johnson Center, University of New Mexico, Albuquerque, NM
87131 United States
Sports Medicine (New Zealand), 1998, 26/3
(145-167)
Glycerol is a naturally occurring 3-carbon alcohol in the
human body. It is the structural backbone of triacylglycerol
molecules, and can also be converted to a glycolytic substrate
for subsequent metabolism. Serum glycerol concentrations
approximate 0.05 mmol/L at rest, and can increase to 0.30
mmol/L during increased lipolysis associated with prolonged
exercise or caloric restriction. When glycerol is ingested or
infused at doses greater than 1.0 g/kg bodyweight, serum
concentrations can increase to approximately 20 mmol/L,
resulting in more than a 10 mOsmol/kg increase in serum
osmolality. Glycerol infusion and ingestion have been used in
research settings for almost 60 years, with widespread
clinical use between 1961 and 1980 in the treatment of
cerebral oedema resulting from acute ischaemic stroke,
intraocular hypertension ( glaucoma ), intracranial
hypertension, postural syncope and improved rehydration during
acute gastrointestinal disease. Since 1987, glycerol ingestion
with added fluid has been used to increase total body water
(glycerol hyperhydration) by up to 700 ml, thereby providing
benefits of improved thermoregulation and endurance during
exercise or exposure to hot environments. Despite the small
number of studies on glycerol hyperhydration and exercise, it
appears to be an effective method of improving tolerance to
exercise and other heat-related stressors.
Medicinal marijuana: A comprehensive review
Gurley R.J.; Aranow R.; Katz M.
Dr. R.J. Gurley, San Francisco Dept. of Public Health, 25 Van
Ness, San Francisco, CA 94102
Journal of Psychoactive Drugs (United States), 1998, 30/2
(137-147)
Considerable controversy exists regarding the role of
marijuana as a therapeutic agent; however, many practitioners
are taught very little about existing marijuana data. The
authors therefore undertook a comprehensive literature review
of the topic. References were identified using textbooks,
review and opinion articles, and a primary literature review
in MEDLINE. Sources were included in this review based
primarily on the quality of the data. Some data exists that
lends credence to many of the claims about marijuana's
properties. In general, however, the body of literature about
marijuana is extremely poor in quality. Marijuana and/or its
components may help alleviate suffering in patients with a
variety of serious illnesses. Health care providers can best
minimize short term adverse consequences and drug interactions
for terminally ill patients by having a thorough understanding
of the pharmacology of marijuana, potential adverse reactions,
infection risks, and drug interactions (along with on-going
monitoring of the patient). For chronic conditions, the
significance and risk of short and long term adverse effects
must be weighed against the desired benefit. Patients who are
best suited to medicinal marijuana will be those who will gain
substantial benefit to offset these risks, and who have failed
a well- documented, compliant and comprehensive approach to
standard therapies.
Vitamins Binf 1 and PP in treating glaucomatous
patients (Russian)
Zhukovsky V.S.
Kaf. Glazn. Bol., Fak. Usover. Vrachej, Med. Inst., L'vov
Russia
Vestnik Oftalmologii 1974, No.3/- (19-21)
The supply of and demand for thiamine were studied in 142
glaucomatous patients. Thiamine deficiency was found in all
these patients, being however more pronounced in cases of
secondary and congestive glaucoma and after antiglaucomatous
operations. Seasonal fluctuations in the supply were recorded.
In winter and spring the thiamine dosages administered daily
were 8 mg parenterally and 12 mg orally, while in summer and
fall they were 6 and 10 mg, respectively. With these doses
saturation of the body supervened on the 2nd to 4th day in
cases of simple glaucoma and on the 4th to 6th day during
glaucoma attacks and after surgery. An improvement of visual
functions could then be observed.
Blood levels of thiamine and ascorbic acid in
chronic open-angle glaucoma.
Asregadoo ER
Ann Ophthalmol (United States) Jul 1979, 11 (7)
p1095-1100
Blood levels of thiamine and ascorbic acid in chronic
open-angle glaucoma are determined in this study. Dietary
vitamin intake was compared with thiamine and ascorbic acid
blood levels in a sample of 38 patients with glaucoma and 12
controls. These patients had a statistically significant lower
thiamine blood level than controls (P less than 0.001), but no
significant difference was found for ascorbic acid blood
levels. Poor absorption of thiamine occurred in the
glaucomatous patients in this study.
Glaucoma, capillaries and pericytes 3. Peptide
hormone binding and influence on pericytes
Ferrari-Dileo G.; Davis E.B.; Anderson D.R.
Bascom Palmer Eye Institute, PO Box 016880, Miami, FL
33101-6880 USA
Ophthalmologica (Switzerland), 1996, 210/5
(269-275)
To test the potential for vasoactive neuropeptide receptors
to affect capillary resistance, we have begun to study the
plausibiIity that pericytes might be equipped to respond to a
representative peptide vasoconstrictor and a representative
peptide vasodilator. Pericytes cultured from the bovine
retinal vasculature specifically bind the angiotensin II (Ang
II) antagonist saralasin (1 nM 125I-saralasin bound at 2.2plus
or minus0.41 fmol/mg protein) and 125I-vasoactive intestinal
peptide (VIP; K(d) of 0.5 nM with a population of 30 fmol/mg
protein). Incubation with 100 microM Ang II induced minimal
cAMP synthesis, while VIP (1 microM, 100 microM) did not
induce any change in cAMP concentration. Ang II (10 microM and
100 microM) caused contraction of pericytes cultured on an
elastic silicone surface. Circulating or locally produced
vasoactive neuropeptides might affect pericyte contractile
tone via several intracellular pathways, moderated by indirect
effects of these peptides through endothelial stimulation,
with the net effect on local blood flow resulting from the
effects on arteries and veins as well as capillaries.
Cultured human trabecular meshwork cells express
functional alpha 2A adrenergic receptors.
Stamer WD; Huang Y; Seftor RE; Svensson SS; Snyder RW; Regan
JW
Department of Pharmacology/Toxicology, University of Arizona,
Tucson 85721, USA.
Invest Ophthalmol Vis Sci (United States) Nov 1996, 37 (12)
p2426-33
PURPOSE: For the treatment of glaucoma, alpha-2 adrenergic
receptor (alpha 2-AR) agonists are thought to lower
intraocular pressure primarily by decreasing aqueous humor
production. Effects on the outflow pathways, however, also may
occur. To begin to examine this possibility, the authors
characterized the alpha 2-AR subtypes present in cultures of
human trabecular meshwork (HTM) cells using both
immunofluorescence microscopy and functional measures of alpha
2-AR activation.
METHODS: For immunofluorescence microscopy,
subtype-specific polyclonal antibodies that recognize each of
the human alpha 2-AR subtypes (alpha 2A, alpha 2B, alpha 2C)
were used. Functional studies involved the inhibition of
forskolin-stimulated cyclic adenosine monophosphate (cAMP)
production, the stimulation of mitogen-activated protein (MAP)
kinase activity, and the stimulation of mitotic activity as
reflected by the expression of proliferating cell nuclear
antigen (PCNA).
RESULTS: From the immunofluorescence microscopy, there was
evidence for the presence of the alpha 2A subtype, but not
alpha 2B or alpha 2C subtype, on HTM cells. The administration
of the alpha 2-agonist, dexmedetomidine, to HTM cells resulted
in a 90% inhibition of forskolin-stimulated cAMP
formation, a twofold stimulation of MAP kinase activity, and a
threefold increase in the expression of PCNA. Additionally,
preincubation of cells with either of the alpha 2-AR-selective
antagonists, rauwolscine or atipamezole, reversed the
functional effects of dexmedetomidine.
CONCLUSIONS: Functional alpha 2A-ARs are present on HTM
cells where they may affect the outflow pathway during the
treatment of glaucoma with alpha 2-AR agonists.
Neurotransmitters and intraocular pressure
Lapalus P.; Elena P.P
Fundam. Clin. Pharmacol. (France), 1988, 2/4
(305-325)
The role of the ocular autonomic nervous system in IOP
regulation has been well established. Pharmacological and
autohistoradiographic studies confirmed the high density of
beta2 and alpha2 receptors on ciliary processes and iris
epithelium. Their respective pharmacological activation or
blockade is discussed. The role of other ocular
neurotransmitters is also complex, as shown by the paradoxical
similar action of dopamine agonists and antagonists on IOP.
Concerning the cholinergic system, ocular muscarinic receptors
are pharmacologically not well documented. Numerous other
neurotransmitters may modulate IOP without necessarily leading
to the development of new drugs. Drugs of the future will
probably concentrate on dopaminergic agonists,
cAMP-stimulators such as forskolin, prostaglandins, and
cannabinoids.
HP 663: A novel compound for the treatment of
glaucoma
Hartman H.B.; Roehr J.E.; Kotyuk B.L.; Kosley R.W. Jr.;
Cherill R.J.; Petko W.W.; Conway P.G.
Department of Biological Research, Hoechst-Roussel
Pharmaceuticals, Somerville, NJ 08876 USA
Drug Dev. Res. (USA), 1988, 12/3-4 (197-209)
Various studies suggest that the 7-dihydroxypropionyl
derivative of forskolin, HP 663, effectively lowers
intraocular pressure (IOP) by a novel mechanism.
Biochemically, HP 663 stimulates rat striatal adenylate
cyclase and displays an affinity for forskolin binding sites
similar to that of forskolin. Following topical administration
this compound lowers IOP in both New Zealand White (NZW) and
Dutch Belt (DB) rabbits. In NZW rabbits, concentrations from
0.05 to 2.0% in a buffered hydroxypropylmethylcellulose (HPMC)
vehicle produce significant reductions in outflow pressures of
35-45% for 5-6 hr. Additionally, HP 663 is soluble in this
vehicle up to a concentration of 0.25%. As mentioned, HP 663
also reduces IOP in DB rabbits; however, this response is not
significant until a concentration of 1% is attained. The
effect on aqueous humor inflow was indirectly determined by
studying the rate of IOP recovery following rapid i.v.
infusion of 20% NaCl. In NZW rabbits, HP 663 significantly
reduced aqueous humor inflow as shown by a 40% decrease in the
IOP recovery rate compared to control. Tolerance also does not
appear to develop to the IOP lowering effects of HP 663 in NZW
rabbits. This compound is still capable of significantly
lowering IOP following twice daily treatment for 21
consecutive days. Following topical administration of
concentrations which effectively lower IOP, HP 663 exhibits no
significant effects on heart rate or blood pressure of NZW
rabbits. Therefore, this compound does not appear to exhibit a
potential for peripheral side effects after topical
application. Based on the results of the present study, HP 663
appears to be a potent activator of adenylate cyclase and may
provide a novel and effective treatment for glaucoma
Intraocular pressure effects of multiple doses of
drugs applied to glaucomatous monkey eyes
Lee P.-Y.; Podos S.M.; Serle J.B.; et al.
Department of Ophthalmology, Mount Sinai School of Medicine,
New York, NY 10029 USA
Arch. Ophthalmol. (USA), 1987, 105/2 (249-252)
The effects of multiple dosing with 0.5% timolol maleate,
2% epinephrine hydrochloride, 4% pilocarpine hydrochloride, 1%
vanadate, 1% forskolin (nonproprietary name, colforsin), or
0.5% prostaglandin F(2alpha) on intraocular pressure (IOP)
were each tested on eight cynomolgus monkey eyes in which
glaucoma was induced by photocoagulating the trabecular
meshwork with the argon laser. The week prior to drug therapy,
baseline IOP measurements were carried out at hourly intervals
from 9:30 AM to 3:30 PM on three days. One to two days later,
therapy was initiated. Each drug was applied topically to both
eyes of each monkey twice daily for at least four days. The
IOP was measured with a calibrated pneumatonometer at the same
hourly intervals on treatment days as on the baseline days.
The IOP at each time of day on treatment days was compared
with the average baseline IOP measured at the corresponding
time of day. Topical application of timolol, epinephrine,
pilocarpine, vanadate, and prostaglandin F(2alpha)
significantly reduced IOP without evidence of tolerance or
tachyphylaxis during the course of therapy. Forskolin did not
significantly decrease IOP after the second day of
treatment.
Laser-induced glaucoma in rabbits
Gherezghiher T.; March W.F.; Nordquist R.E.; Koss M.C. Dean
A.
McGee Eye Institute, Oklahoma City, OK 73104 USA
Exp. Eye Res. (UK), 1986, 43/6 (885-894)
Argon laser energy was applied to the trabecular meshwork
of pigmented rabbits in an attempt to develop an animal model
of 'glaucoma'. Laser energy was varied to determine the
optimal level needed to produce sustained ocular hypertension.
An initial response of ocular hypertension followed by
hypotension was observed in all of the animals tested.
Approximately half of the laser-treated rabbits developed a
secondary buphthalmus and sustained ocular hypertension. In
these animals outflow facility was decreased by approximately
60%. Histologic examination at 4-and 8 weeks after laser
treatment demonstrated a wound-healing response resulting in
closure of the intertrabecular spaces and obstruction of
outflow to injected carbon particles. Optic nerve cupping and
a loss of ganglion cells were also observed. Topical
application of L-timolol (0.5%), pilocarpine (2.0%) and
forskolin (1.0%) were found to be effective in decreasing
intraocular pressure in the laser-treated, hypertensive eye
with no significant effect in control non-laser-treated eyes,
suggesting that this model can be a useful tool for screening
potential antiglaucoma medications.
Regulation of aqueous flow by the adenylate cyclase
receptor complex in the ciliary epithelium
Sears M.L.
Department of Ophthalmology and Visual Science, Yale
University School of Medicine, New Haven, CT 06510 USA
Am. J. Ophthalmol. (USA), 1985, 100/1 (194-198)
The answer to how beta-adrenergic receptor mediates a fall
in intraocular pressure has been elusive. Methods of
measurement have not been refined sufficiently. The separate
changes after adrenergic treatment frequently are small, and
the tissue effects are multiple. On a molecular basis,
stimulation of the beta-adrenergic receptor activates
intracellular adenylate cyclase to produce increased cyclic
adenosine monophosphate. Acting by different cell-receptor
mechanisms, but nonetheless potent, nonadrenergic stimulators
of adenylate cyclase in the ciliary epithelium, such as
cholera toxin and organic fluorides, have been studied in
experimental animals. They reduce intraocular pressure by
reducing net aqueous flow. When forskolin, a diterpene and
potent stimulator of adenylate cyclase, became available, it
was used in noninvasive topical form in the human eye to
clarify the question of whether increased cyclic adenosine
monosphosphate reduces intraocular pressure and aqueous flow.
Noninvasive studies in human eyes have demonstrated a 35%
reduction in outflow pressure after the administration of
forskolin in a 1% topical suspension, matched by a
corresponding reduction in aqueous flow. Tonographic outflow
facility was unaltered. Thus, the entire reduction in
intraocular pressure can be accounted for by a reduction in
net aqueous flow.
Forskolin suppresses sympathetic neuron function
and causes ocular hypotension
Potter D.E.; Burke J.A.; Temple J.R.
Department of Pharmacology, Texas Tech University Health
Sciences Center, Lubbock, TX 79430 USA
Curr. Eye Res. (England), 1985, 4/2 (87-96)
No abstract.
Forskolin lowers intraocular pressure by reducing
aqueous inflow
Caprioli J.; Sears M.; Bausher L.; et al.
Department of Ophthalmology and Visual Science, Yale
University School of Medicine, Box 3333, New Haven, CT 06510
USA
Invest. Ophthalmol. Visual Sci. (USA), 1984, 25/3
(268-276)
Forskolin is a diterpene derivative of the plant Coleus
forskohlii that stimulates adenylate cyclase activity without
interacting with cell surface receptors. Forskolin lowers the
intraocular pressure of rabbits, monkeys, and humans. In
rabbits, net aqueous humor inflow decreases, outflow facility
remains unchanged, and ciliary blood flow increases. Tolerance
to the intraocular pressure lowering effect did not occur in
rabbits after topical doses given every 6 hr for 15 days. In
vitro forskolin activates adenylate cyclase of crude
particulate homogenates prepared from cultured human ciliary
epithelia or from dissected ciliary epithelial processes of
rabbit or human eyes. This activation is not blocked by
timolol. The stimulation of adenylate cyclase by isoproterenol
in vitro is potentiated in the presence of forskolin.
Forskolin represents a potentially useful class of
antiglaucoma agents differing in molecular mechanism of action
from previously used drugs.
Indomethacin and epinephrine effects on outflow
facility and cyclic adenosine monophosphate formation in
monkeys
Crawford K.S.; Gange S.J.; Gabelt B.T.; Heideman W.; Robinson
J.C.; Hubbard W.C.; Kaufman P.L.
Ophthalmology/Visual Sciences Dept., University of Wisconsin,
600 Highland Avenue, Madison, WI 53792-3220 USA
Investigative Ophthalmology and Visual Science (USA), 1996,
37/7 (1348-1359)
Purpose. To investigate the effect of indomethacin
inhibition of prostanoid production on the
epinephrine-stimulated increase in outflow facility and cyclic
adenosine monophosphate (cAMP) production in the anterior
segment of the monkey eye.
Methods. Topical indomethacin was given 1 hour before the
intracameral administration of epinephrine to living
cynomolgus monkeys. Outflow facility was measured for 45 to 60
minutes, beginning 3 hours after epinephrine administration,
by two-level constant pressure perfusion of the anterior
chamber. Cyclic adenosine monophosphate formation was measured
in cell membranes isolated from rhesus monkey ciliary muscle,
ciliary muscle, ciliary processes, trabecular meshwork, and
iris in the presence of forskolin, indomethacin, epinephrine,
or indomethacin and epinephrine combined.
Results. Three hours after the intracameral administration
of 5.5 microg epinephrine, facility increased by similar40%, a
putatively maximal response, at which time the intracameral
epinephrine concentration was similar15 microM. Pretreatment
with topical indomethacin produced a dose-dependent inhibition
of epinephrine's facility-increasing effect; the maximum
inhibition of 50% to 70% occurred at an indomethacin dose of
50 to 125 microg. Doubling the indomethacin dose (250 microg)
produced no further inhibition, whereas a fivefold larger
epinephrine dose (27.5 microg) did not overcome the
inhibition. Forskolin and epinephrine both stimulated cAMP
production in vitro, whereas (indomethacin) greater than or
equal to 10-4 M partially inhibited both basal and
epinephrine-stimulated cAMP production in all four
tissues.
Conclusions. Approximately half of the epinephrine-induced
facility increase is inhibited by indomethacin, but it is
unclear whether the indomethacin- inhibitable fraction is
mediated by epinephrine-stimulated prostanoid production or
release.
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