Re: HELP! I CAN'T SLEEP!

[Guest guest]

Aside from other drugs, there are a number of agents that may help you to

sleep and be a healthier alternative.

One is melatonin. You can start with a 1 mg dose at night and go up to

about 5 mg or so to see if it helps.

Ambien is a crappy sleep aid--at best, it works for about 4 hours. And it's

addictive and hard to get off, as are most antidepressants. One

interesting drug that may lower LPS levels is " Sonata " - however, it is

extensively metabolized by the CYP3A4 system. See

http://www.fda.gov/medwatch/SAFETY/2003/03May_PI/Sonata_PI.pdf

Some info on melatonin and HIV below.

Attending to damaged gut function due to HIV infection may help if it can

be shown to reduce lipopolysaccharide levels. I'd say a small dose of

glutamine and probiotics like acidophilus or S. boulardii may help though

this remains unproven. Part of the problem is an activated state of the

immune system (the Gut Associated Lymphoid Tissue has about 80% of the T

cells in it). Given the connections between the immune and neurological

systems, it's not unreasonable to hypothesize that there can be an

interaction with psychological effects and insomnia.

M.

***

Maestroni GJ. Therapeutic potential of melatonin in immunodeficiency

states, viral diseases, and cancer. Adv Exp Med Biol. 1999;467:217-26.

Istituto Cantonale Di Patologia, Center For Experimental Pathology,

Locarno, Switzerland. icpcps@...

Maintenance of health depends on the ability to respond appropriately to

environmental stressors via reciprocal interactions between the body and

the brain. In this context, it is well recognized that the pineal hormone

melatonin (MLT) plays an important role. T-helper cells bear

G-protein-coupled MLT cell membrane receptors and, perhaps, MLT nuclear

receptors. Activation of MLT receptors enhances the release of T-helper

cell cytokines, such as gamma-interferon and interleukin-2 (IL-2), as well

as activation of novel opioid cytokines which crossreact immunologically

with both interleukin-4 and dynorphin B. MLT has been reported also to

enhance the production of interleukin-1, interleukin-6 and interleukin-12

in human monocytes. These mediators may counteract secondary

immunodeficiencies, protect mice against lethal viral and bacterial

diseases, synergize with IL-2 against cancer and influence hematopoiesis.

Hematopoiesis is influenced by MLT-induced-opioids (MIO) acting on kappa

1-opioid receptors present on bone marrow macrophages. Clinically, MLT

could amplify the anti-tumoral activity of low dose IL-2, induce objective

tumor regression, and prolong progression-free time and overall survival.

MLT seems to be required for the effectiveness of low dose IL-2 in those

neoplasias that are generally resistant to IL-2 alone. Similar findings

were obtained in a study in which MLT was combined with gamma-interferon in

metastatic renal cell carcinoma. In addition, MLT in combination with

low-dose IL-2 was able to neutralize the surgery-induced lymphocytopenia in

cancer patients. IL-2 treatment in patients results in activation of the

immune system and creates the most suitable biological background for MLT.

The finding that MLT stimulates IL-12 production from human monocytes only

if incubated in presence of IL-2 further supports this concept. On the

other hand, high concentrations of MLT have been found in human breast

cancer tissue. The MLT concentration, which was 3 orders of magnitude

higher than that present in the plasma, correlated positively with good

prognostic markers such as estrogen receptor status and nuclear grade.

Whether this relates to the immunoneuroendocrine action of MLT remains to

be established. Clinical studies are needed on the effect of MLT in

combination with IL-2 or other cytokines in cancer patients and viral

diseases including HIV-infected patients.

***

Neuroimmunotherapy with low-dose subcutaneous interleukin-2 plus melatonin

in Lissoni P, Vigore L, Rescaldani R, Rovelli F, Brivio F, Giani L, Barni

S, Tancini G, Ardizzoia A, Vigano MG. AIDS patients with CD4 cell number

below 200/mm3: a biological phase-II study. J Biol Regul Homeost Agents.

1995 Oct-Dec;9(4):155-8.

Divison of Oncological Radiotherapy, San Gerardo Hospital, Monza, Milano,

Italy.

A phase-II pilot clinical study was performed to evaluate the effects of

low-dose subcutaneous IL-2 with the pineal hormone melatonin (MLT) in AIDS

patients with CD4 counts below 200/mm3. The study included 11 patients.

IL-2 was given subcutaneously at 3 million IU/ day in the evening for 6

days/week for 3 weeks. MLT was given orally at 40 mg/day in the evening

every day, starting 7 days prior to IL-2. The treatment was substantially

well tolerated, and in particular no cardiovascular or pulmonary

complication occurred. An increase in CD4 cell number greater than 30%

occurred in 4/11 (36%) patients, and CD4 cell mean values observed during

the study were significantly higher with respect to those found before. In

addition, the treatment induced a significant increase in mean number of

lymphocytes, eosinophils, T lymphocytes, NK cells, CD25- and DR-positive

lymphocytes. Finally, CD4/CD8 mean ratio significantly increased during the

study. This preliminary clinical study suggests that the combined

neuroimmunotherapy with low-dose subcutaneous IL-2 and MLT may improve the

immune status also in AIDS patients with CD4 cell counts below 200/mm3, who

generally do not respond to IL-2 alone.

***

Nunnari G, Nigro L, Palermo F, Leto D, Pomerantz RJ, Cacopardo

B. Reduction of serum melatonin levels in HIV-1-infected individuals'

parallel disease progression: correlation with serum interleukin-12 levels.

Infection. 2003 Dec;31(6):379-82.

The Dorrance H. Hamilton Laboratories, Center for Human Virology, Division

of Infectious Diseases, Dept. of Medicine, Jefferson Medical College,

Jefferson University, Philadelphia, PA 19107, USA. gnunnari@...

BACKGROUND: During the natural history of human immunodeficiency virus type

I (HIV-1) infection, an impairment of interleukin-12 (IL-12) production

precedes a switch from a T-helper 1 (Th1) to a T-helper 2 (Th2) stage of

cellular immunity. Melatonin, the main hormone produced by the pineal

gland, seems to promote a Th1 response by increasing the production of

IL-12 in vitro. The aim of this study was to measure and correlate serum

levels of melatonin and IL-12 in a cohort of HIV-1-infected individuals.

PATIENTS AND METHODS: 77 anti-HIV-1-positive subjects were enrolled: 20

were in CDC stage A, 25 in CDC stage B and 32 in CDC stage C. 30 healthy

HIV-1-seronegative subjects were recruited as controls. IL-12 and melatonin

concentrations were quantitated in serum samples. RESULTS: Mean levels of

serum melatonin were significantly lower in HIV-1-infected individuals in

comparison with controls (p < 0.001). Within the HIV-1-seropositive group,

mean melatonin and IL-12 concentrations were significantly lower in

patients in CDC stage C, as compared with patients in CDC stages B and A (p

< 0.01). CONCLUSION: During the natural history of HIV-1 disease, serum

melatonin levels are progressively reduced. This reduction may be related

to the impairment of Th1 immunoresponses.

***

Kast RE, Altschuler EL. Co-administration of ramelton and fluvoxamine to

increase levels of interleukin-2. Med Hypotheses. 2006;67(6):1389-90. Epub

2006 Aug 8.

Department of Psychiatry, University of Vermont, 2 Church Street,

Burlington, VT 05401, United States. recast@...

Ramelton is a medication recently approved by the FDA for treatment of

insomnia. Ramelton is an analogue of melatonin with a higher affinity even

than that of the natural ligand. Clinically this potentially strong effect

of the ligand is blunted by the fact that upon oral ingestion there is

first pass metabolism of greater than 95%. This liver metabolism is

mediated by the CYP1A2 enzyme. It turns out that the medication fluvoxamine

approved by the FDA for the treatment of obsessive compulsive disorder is a

potent inhibitor of the CYP1A2 enzyme, with the effect that

co-administration of ramelton and fluvoxamine increases blood levels of

ramelton by 100-200 fold. It turns out that lymphocytes bear the melatnonin

receptors and stimulation of these receptors on lymphocytes cause the

lymphocytes to elaborate the pro-inflammatory cytokine interleukin-2

(Il-2). Thus, here we point out that co-administration of ramelton and

modest doses of fluvoxamine may be able to smoothly produce increased

levels of Il-2, this may be useful in diseases and conditions such as

metastatic cancer and maintenance of suppression of the HIV virus.