Re: IOWA group (HCQ/Fluconazole/Mino/Schardt)

[Guest guest]

On Monday, March 14, 2005, at 09:24 AM, Barb Peck wrote:

>

> I've been reviewing the papers which indicate that of raising the PH

> in the cell may allow for synergistic killing at lower doses of some

> abx in combo.

>

> From my own experience, I know this is true for HCQ

> (Hydroxychloroquine) and Mino. 

That's basically the protocol Sam Donta uses. He wrote " Macrolide

Therapy of Chronic Lyme Disease. " He said HCQ helps macrolide

antibiotics but he does not believe (in that paper anyway) that it

helps mino. My son is on Zithromax and HCQ now.

- Kate D.

[Guest guest]

Barb,

It looks, from what I've heard that Sam Donta seems to have a good technique for making his protocol work: he "patient casts" and if they sound like they won't be easy, simple straight forward Lyme patients (ie no complex co-infections) he doesn't take them on, or he fires them.

If all LLMDs did this, they'd all have fantastic results. He has his macrolide + HCQ/tetra regimen, if it suits you, good, if not you're out. He fits the patient to the regimen not (as one would expect) the regimen to the patient

Nelly

[infections] IOWA group (HCQ/Fluconazole/Mino/Schardt)

Kate: I know - I've read Donta's theories and "Macrolide therapy...(and I talked to him in 2002 - but he did not take me on as a patient - my case was too complicated).

[Guest guest]

I thought you must have read it, but I posted just in case you (or

others) hadn't.

- Kate D.

On Monday, March 14, 2005, at 11:36 AM, Barb Peck wrote:

>

> Kate:

>

> I know -  I've read Donta's theories and " Macrolide therapy...(and I

> talked to him in 2002 - but he did not take me on as a patient - my

> case was too complicated).

[Guest guest]

Most of the folks in the midwest using fluconazole aren't combining

it with HCQ. Several are using mino or doxy though.

I think I know of one individual that is combining fluconazole and

HCQ and she has responded well to fluconazole. I think she has only

taken it for a few weeks though.

The idea of using fluconazole & mino/doxy in combo with HCQ is

worthy of investigating.

Combining and modifying Donta's and Schardts regimens sounds

reasonable and may be quite effective.

>

> I've been reviewing the papers which indicate that of raising the

PH

> in the cell may allow for synergistic killing at lower doses of

some

> abx in combo.

>

> From my own experience, I know this is true for HCQ

> (Hydroxychloroquine) and Mino.

> The papers below indicate it's true for HCQ/fluconazole (at least

in

> the petrie dish).

>

> **** What is the opinion from the IOWA group..???????? ***

> Are you guys finding this to be true? Have you adjusted the doses

> downward?? DID you baseline prior to treatment for Candida?

>

> Thanks,

> Barb

>

>

>

> Referring to message #217:

>

> Looks like the dose of fulconazole can be reduced when the PH is

> raised in the cell.

>

> This is the same theory as Sam Donta's Lyme therapy -using HCQ to

> alkalize the cell compartment so one of the tetracyclines can enter

> the cell compartment and kill the intra cellular pathogen.

>

> Anyone taken HCQ and fluconazole together?- what about Schardt's

> IOWA group-?

>

> I did hear from someone in the Iowa group - they're on HCQ/Mino?

> fluconazole

>

>

>

>

> > Pharm Res. 2004 Dec;21(12):2207-12. >

> >

> > Prophylactic role of liposomized chloroquine against murine

> > cryptococcosis less susceptible to fluconazole.

> >

> > Khan MA, Jabeen R, Mohammad O.

> >

> > Aligarh Muslim University, Aligarh 202002, India.

> > alammasood1@r...

> >

> > PURPOSE: The prophylactic role of liposomized chloroquine

> (lip-CQ)

> > has been assessed against less susceptible Cryptococcus

> neoformans

> > infection in murine model. METHODS: In the current study, we

> > investigated the antifungal activity of lip-CQ against C.

> neoformans

> > in macrophages cell line (J 774) and murine model. Mice were

> > pretreated with free as well as liposomized formulations of CQ

> at

> > various doses. The anticryptococcal activity of fluconazole was

> > compared in mice with or without CQ pretreatment. The

> efficacy of CQ

> > prophylaxis was assessed by survival as well as colony

> forming units

> > (cfu) in brain and lungs of treated mice. RESULTS:

> Fluconazole alone

> > was not found significantly effective against C. neoformans in

> both

> > in vitro and in vivo studies. However, the antifungal activity of

> > fluconazole increases in chloroquine-pretreated mice. Lip-CQ

> was

> > found to be more effective in comparison to the same dose of

> free

> > chloroquine in reducing fungal burden from macrophages in

> vitro and

> > lungs and brain of C. neoformans infected mice.

> >

> > CONCLUSIONS: The enhanced prophylactic activity of lip-CQ

> seems due

> > to rapid uptake of drug-containing liposomes by macrophages.

> The

> > liposome-mediated accumulation of CQ in macrophages

> makes the

> > environment unfavorable (alkaline) for the intracellular

> > multiplication of C. neoformans. Moreover, the increased

> incidence of

> > multi-drug resistance and diversity of pathogenic

> microorganisms

> > inhibited or killed by CQ makes it the drug of choice for

> > prophylactic therapy.

> >

> >

> __________________________________________________

> _______________

> >

> > J Antimicrob Chemother. 2005 Feb;55(2):223-8. Epub 2004

> Dec 08.

> > Related Articles, Links

> >

> >

> > Enhanced anticryptococcal activity of chloroquine in

> > phosphatidylserine-containing liposomes in a murine model.

> >

> > Khan MA, Jabeen R, Nasti TH, Mohammad O.

> >

> > Interdisciplinary Biotechnology Unit, Aligarh Muslim University,

> > Aligarh-202002, India.

> >

> > OBJECTIVES: The anticryptococcal activity of chloroquine was

> assessed

> > after incorporation in phosphatidylserine (PS)-containing

> negatively

> > charged liposomes in a murine model. METHODS: In the

> present study,

> > we investigated the antifungal activity of chloroquine entrapped

> in

> > PS liposomes against Cryptococcus neoformans in the

> macrophage cell

> > line J 774 and in a murine model. Mice were treated with free

> as well

> > as liposomal formulations of chloroquine before and after

> challenging

> > with C. neoformans infection. The anticryptococcal activity of

> > chloroquine was also evaluated in combination with

> fluconazole in the

> > treatment of systemic murine cryptococcosis. The efficacy of

> > chloroquine treatment was assessed by continued survival as

> well as

> > by colony forming units (cfu) in liver and brain of treated mice.

> > RESULTS: Chloroquine entrapped in PS liposomes shows

> increased

> > activity against C. neoformans infection both in in vitro and in

> vivo

> > studies. Moreover, the antifungal activity of fluconazole

> increases

> > when used in combination with liposomal chloroquine.

> Chloroquine in

> > PS liposomes was found to be more effective in comparison

> with the

> > same dose of free chloroquine or chloroquine entrapped in

> neutral

> > liposomes.

> >

> > CONCLUSIONS: The enhanced anticryptococcal activity of

> chloroquine in

> > PS liposomes seems to be due to uptake of drug-containing

> PS

> > liposomes by macrophages. It can be assumed that

> liposome-mediated

> > delivery of chloroquine to macrophages results in an

> unfavourable

> > (alkaline) environment for the growth of C. neoformans inside

> > macrophages.

> >

> > PMID: 15590713 [PubMed - in process]

> >

> > PMID: 15648251 [PubMed - in process]

>

>

> AND MORE ON HCQ and immune modulation:

>

> more on HCQ- PH and immune modulation

>

>

> ADVERTISEMENT

>

>

>

>

>

>

> Mol Cell Biol. 2005 Feb;25(3):1025-40. Inhibition of macroautophagy

> triggers apoptosis.

>

> Boya P, -Polo RA, Casares N, Perfettini JL, Dessen P,

> Larochette N, Metivier D, Meley D, Souquere S, Yoshimori T, Pierron

> G, Codogno P, Kroemer G.

>

> CNRS-UMR 8125, Institut Gustave Roussy, Pavillon de Recherche 1, 39

> rue Camille-Desmoulins, F-94805 Villejuif, France. kroemer@i....

>

> Mammalian cells were observed to die under conditions in which

> nutrients were depleted and, simultaneously, macroautophagy was

> inhibited either genetically (by a small interfering RNA targeting

> Atg5, Atg6/Beclin 1-1, Atg10, or Atg12) or pharmacologically (by 3-

> methyladenine, hydroxychloroquine, bafilomycin A1, or monensin).

Cell

> death occurred through apoptosis (type 1 cell death), since it was

> reduced by stabilization of mitochondrial membranes (with Bcl-2 or

> vMIA, a cytomegalovirus-derived gene) or by caspase inhibition.

Under

> conditions in which the fusion between lysosomes and autophagosomes

> was inhibited, the formation of autophagic vacuoles was enhanced

at a

> preapoptotic stage, as indicated by accumulation of LC3-II protein,

> ultrastructural studies, and an increase in the acidic vacuolar

> compartment. Cells exhibiting a morphology reminiscent of

> (autophagic) type 2 cell death, however, recovered, and only cells

> with a disrupted mitochondrial transmembrane potential were beyond

> the point of no return and inexorably died even under optimal

culture

> conditions. All together, these data indicate that autophagy may be

> cytoprotective, at least under conditions of nutrient depletion,

and

> point to an important cross talk between type 1 and type 2 cell

death

> pathways.

>

> PMID: 15657430 [PubMed - in process]

> ________________________________________________________________

> Gut. 1982 Mar;23(3):181-7. Related Articles, Links

>

>

> Inhibition of leucocyte motility and prevention of immune-complex

> experimental colitis by hydroxychloroquine.

>

> JM, McLaughlin JE, Brown DJ, Nuttall LA, Jewell DP.

>

> The inhibitory effects of hydroxychloroquine on leucocyte motility

> have been compared with those of prednisolone. It has been shown to

> have similar potency to prednisolone as an inhibitor of human

> neutrophil and monocyte motility. Hydroxychloroquine has then been

> compared with placebo in the prevention of an immune-complex

> experimental colitis in rabbits. Rectal biopsies were taken from

> rabbits 24 hours after initiation of colitis, coded, and graded

> histologically. The summated gradings for acute inflammation and

> goblet cell depletion had worsened more in the control rabbits

(mean

> grade +6.7) than in the treated rabbits (mean grade +1.8) P less

than

> 0.05. There was no difference in the mononuclear cell infiltrate

> between the two groups. Hydroxychloroquine, which is a potent

> inhibitor of leucocyte motility, effectively prevents the acute

> inflammatory infiltrate in this experimental colitis model and

> therefore merits trial in human ulcerative colitis.

>

> PMID: 7068043 [PubMed - indexed for MEDLINE]

>

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