PARS:
Jenna,
Have a friend who does research in the biotech industry see what she could find on this small cap. Here's her results, confirming your earlier reports, fwiw:
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I checked the Bausch Lomb web site and yes they have information about Loteprednol. And yes, it does cause less IOP than other steroids, though it is less effective than prednisolone, another topical steroid.
In terms of traumatic brain injury, I did some research on the web and at Medline. ITs seems that HU-211 (dexanabinol) has only been studied in animals. However, the existence of published animal studies and published animal studies is a good sign. Although what really counts are the clinicals (Phase III) . It is probable that dexanabinol is a A VERY long way off from any clinical indications. The cytokine effects may be real but its quite theoreitcal at this point (see below)No mention of drug on website of Food and Drug Administration * Center for Drug Evaluation and Research
FROM WEB SITE ON TBI
ANOXIC BRAIN INJURY refers to damage caused to the brain when its oxygen supply is cut off. In general, this occurs
when there is an absence of oxygen intake (no breathing) or an impairment in oxygen transport by the blood stream. Anoxic
brain injury can occur along with cardiac arrest, as a complication of surgery, or as a result of near-drowning.
When the flow of oxygen to the brain is interrupted even for just a few minutes, serious, irreversible damage can occur.
While traumatic brain injury can result in bruising and swelling of the brain , anoxic brain injury causes brain cells to die.
The sequela of anoxic brain injury (the physical and cognitive impairments) resemble those of other types of brain trauma.
Rehabilitation for anoxic brain injury involves many of the same therapies as traumatic brain injury... physical therapy,
cognitive therapy, occupational therapy, etc. The prognosis for someone with anoxic brain injury depends upon pre-morbid
factors (e.g., pre-injury heart condition), the injury (e.g., length of time of anoxia), and treatment (e.g., intensity and
quality of therapy).
If you are not familiar with Medline, here is description
MEDLINE (MEDlars onLINE)
is the National Library of Medicine's (NLM) premier bibliographic database covering the fields of medicine, nursing,
dentistry, veterinary medicine, the health care system, and the preclinical sciences.
contains bibliographic citations (e.g., authors, title, and journal reference) and author abstracts from over 3,900 biomedical
journals published in the United States and 70 foreign countries during the current four years. The process of selecting journals
for inclusion is described in the Fact Sheet, Journal Selection for Index Medicus/MEDLINE.
contains over 9 million records dating back to 1966.
has worldwide coverage, but 88% of the citations in current MEDLINE are to English-language sources and 76% have English
abstracts.
contains the citations that appear in Index Medicus, as well as the citations of "special list" journals. Special list journals
include those indexed for the Index to Dental Literature and the International Nursing Index. Citations for MEDLINE are
created by the National Library of Medicine, International MEDLARS partners, and cooperating professional organizations.
ONE OF ABOUT 7 ANIMAL ABSTRACTS
FROM MEDLINE
Ann N Y Acad Sci 1999;890:505-14
Neuroprotective effects of HU-211 on brain damage resulting from soman-induced
seizures.
Filbert MG, Forster JS, Smith CD, Ballough GP
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400, USA.
Margaret.Filbert@AMEDD.Army.Mil
[Medline record in process]
Neuroprotective effects of HU-211 (dexanabinol), a synthetic nonpsychotropic analog of tetrahydrocannabinol, on brain damage resulting from
soman-induced seizures were examined in male Sprague-Dawley rats challenged with 1.6 LD50 soman. At 5 or 40 min after onset of seizures, the
rats were given an intraperitoneal injection of 25 mg/kg HU-211. All rats that received soman showed electrocorticographic (ECoG) evidence of
sustained seizures and status epilepticus for 4-6 hr. HU-211 had no effect on either the strength or duration of seizure activity. Administration of
HU-211 at 5 min after seizure onset reduced median lesion volume 86% (as assessed by microtubule-associated protein 2 (MAP2)-negative
staining), and when administered 40 min post-onset, the reduction in necrosis was 81.5% despite the presence of continuous seizures for 4-5 hr.
These observations were corroborated by hemotoxylin and eosin (H&E) histopathological assessment that showed a significant reduction in piriform
cortical neuronal damage in HU-211-treated animals. It is concluded that HU-211 provides considerable neuroprotection against brain damage
produced by soman-induced seizures.
CHECK THIS OUT!!!!!!
J Neuroimmunol 1997 Feb;72(2):169-77
Cytokine production in the brain following closed head injury: dexanabinol
(HU-211) is a novel TNF-alpha inhibitor and an effective neuroprotectant.
Shohami E, Gallily R, Mechoulam R, Bass R, Ben-Hur T
Department of Pharmacology, Hebrew University, School of Pharmacy, Jerusalem, Israel. esty@yam-suff.cc.huji.ac.il
Traumatic brain injury triggers a cascade of events resulting in delayed edema, necrosis and impaired function. Harmful mediators are accumulating
in the brain after injury and recently, the role of cytokines in the pathophysiology of brain injury has been suggested. We have developed an
experimental model for closed head injury (CHI), in which edema, blood-brain-barrier disruption, motor and memory dysfunctions have been
demonstrated. In this study, spatial and temporal induction of IL-1, IL-6 and TNF-alpha gene mRNA transcription and of TNF-alpha and IL-6
activity in rat brain after CHI are shown. Dexanabinol, HU-211, is a synthetic cannabinoid devoid of cannabimimetic effects; it exhibits
pharmacological properties of N-methyl-D-aspartate (NMDA)-receptor antagonist and is an effective cerebroprotectant. We report here that HU-211
is a novel inhibitor of TNF-alpha production at a post-transcriptional stage. HU-211, pentoxyfilline and TNF-binding protein improved the outcome
of CHI. We suggest that TNF-alpha is a primary mediator of neurotoxicity after CHI, as inhibition of TNF-alpha is associated with better clinical
recovery. TNF-alpha modulating agents, if given within the early time window post-injury, may improve the final neurological outcome in victims
of brain trauma.
Publication Types:
Review
Review, tutorial
PMID: 9042110, UI: 97194672 |
