Monday, February 28, 2011

A paradigm linking herpesvirus immediate-early gene expression apoptosis and ME

A paradigm linking herpesvirus immediate-early gene expression apoptosis and myalgic encephalomyelitis chronic fatigue syndrome

Authors: A Martin Lerner, Safedin Beqaj:

Published Date February 2011 ,
1Department of Medicine, William Beaumont Hospital, Royal Oak, MI, USA; 2DCL Medical Laboratories, Indianapolis, IN, USA

Abstract:
There is no accepted science to relate herpesviruses (Epstein–Barr virus [EBV], human cytomegalovirus [HCMV], and human herpesvirus 6 [HHV6]) as causes of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS).

ME/CFS patients have elevated serum immunoglobulin (Ig)G serum antibody titers to EBV, HCMV, and HHV6, but there is no herpesvirus DNA-emia, herpesvirus antigenemia, or uniformly elevated IgM serum antibody titers to the complete virions. We propose that herpesvirus EBV, HCMV, and HHV6 immediate-early gene expression in ME/CFS patients leads to host cell dysregulation and host cell apoptosis without lytic herpesvirus replication.

Specific antiviral nucleosides, which alleviate ME/CFS, namely valacyclovir for EBV ME/CFS and valganciclovir for HCMV/HHV6 ME/CFS, inhibit herpesvirus DNA polymerases and/or thymidine kinase functions, thus inhibiting lytic virus replication. New host cell recruitment thus ceases. In the absence of new herpesvirus, nonpermissive herpesvirus replication stops, and ME/CFS recovery ensues.

See also: If you take longterm Valtrex - READ THIS! or See also: Herpesvirus antiviral treatment reversed CFS illness in 79 of 106 Group A CFS patients

FULL article

PS: from their earlier research:
Valacyclovir (or famciclovir) for EBV
Both valacyclovir and famciclovir were given as 1 gm (14.3 mg/kg) every six hours.
When the patient weighed 79.5 kg, 1500 mg valacyclovir (or famciclovir) was given every six hours. Maximum acyclovir levels are present after 90–120 minutes (7.9–21 g/mL).29
Valacyclovir is excreted by renal glomerular filtration and tubular secretion. The elimination half-lives of acyclovir and penciclovir are in the range of 1.5–6 hours. Patients were instructed to drink at least 1500 mL of water daily to avoid valacyclovir-induced renal calculi. At the physician’s discretion, cimetidine (400 mg every 12 hours) and/or probenecid (500 mg every 12 hours) which inhibit(s) acyclovir tubular secretion were given to increase acyclovir serum levels.32,34
Valacyclovir and famciclovir do not effectively inhibit HCMV or HHV6 multiplication. In order to continue therapy, normal CBC, platelet count, aminotransferases, and urinalysis were required at physician visits every 4–6 weeks.

Valganciclovir for HCMV and/or HHV6
The valganciclovir ID50 for HCMV and HHV6 is 0.2– 2.8 g/mL. The ID50 for ganciclovir versus EBV is 0.5 g/mL.35 In this study valganciclovir was used for CFS patients with suspected HCMV or HHV6 infections. Valganciclovir is efficiently absorbed as ganciclovir, inhibiting human bone marrow progenitor cells and lymphocyte blastogenesis. After 0.5–1.0 gm doses, the average peak valganciclovir concentration
(Cmax) is 6.1 g/mL. Valganciclovir was also given after meals, thereby increasing its bioavailability. Valganciclovir was started at 450 mg once daily in the morning after food for three days, and then continued as two in the morning for three days; and finally given, two in the morning followed by 450 mg 12 hours later as a continuing dose. If elevated aminotransferase(s) occurred, valganciclovir was withheld for 1–2 weeks until
serum transaminases were normal. Valganciclovir was then continued 900 mg once daily. If the patient weighed .91 kg, 900 mg valganciclovir was given every 12 hours.

Toxicity
At 4–6 week visits, recorded entries were made for abnormal white blood cells, platelet counts, aminotransferases, participation in a smaller, randomized, blinded, placebo-controlled trial, weight gain or loss, substitution of famciclovir for valacyclovir, and any changes in dosage of valganciclovir, valacyclovir, or famciclovir.30

1 comment:

arun kumar said...

Valacyclovir is an antiviral drug. It slows the growth and spread of the herpes virus so that the body can fight off the infection. It will not cure herpes, but it can lessen the symptoms of the infection.

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