Nanobacteria (NB) or so called calcifying nanoparticles, were isolated and
named by the Finnish researcher Olavi Kajander and the Turkish researcher Neva
Ciftcioglu, working at the University of Kuopio in Finland (Kajander
and Ciftcioglu, 1998). According to Kajander and Ciftcioglu, the particles
are self-replicating bacteria and the smallest described bacteria to date, with
dimensions of 20-200 nm in length. Furthermore, these organisms were found to
produce a biofilm containing hydroxyl apatite or carbonate, preventing their
effective staining. NB are phylogenetically close relatives of mineral forming
bacteria (Kajander et al., 1997). These particles
have been isolated from kidney stones and urine of patients with renal lithiasis
(Ciftcioglu et al., 1999), renal fluid taken
from patients with polycystic kidneys, the biliary tract in patients with cholecystitis
(Wen et al., 2005), inclusions of psammoma in
ovarian cancers (Hudelist et al., 2004), peripheral
blood from healthy subjects and atheromatous plaques (Bratos-Perez
et al., 2008). NB are thought to play an important role in extraskeletal
calcifying diseases including stones formation, urolithiasis and polycystic
kidney disease (Kajander et al., 2003), atherosclerosis
(Jelic et al., 2007), periodontal disease (Ciftcioglu
et al., 2003), rheumatoid arthritis (Cassell,
1998) and prostatitis (Bock et al., 1989;
Geramoutsos et al ., 2004). The stimuli for
calcium salt deposition in patients with these conditions are unclear but nidi
(meaning that biomineralization is taking place out of chemical equilibrium)
for precipitation and crystallization are needed even under supersaturation
conditions Carson (1998). Two strains, one of Nanobacterium
sanguineum and the other of Nanobacterium sp., were isolated from
kidney stones and human and bovine sera, respectively Kajander
et al . (1997). NB are so hard to remove and treat because of their
calcified shells, outer coverings made of heavy, resistant substances (protective
shell) that keep the NB inside from the purging drugs and immune system. Nanobacteria
cannot be killed by penicillin, cephalosporins, marolides and most other antibiotics,
heat under 196 F, freezing, dehydration and gamma radiation under 150 Mrad (Demir,
2008). In this review, we discuss the different trials for inhibition and
treating NB with various chemotherapeutic and naturally product agents.
DIFFERENT PHASES FOR GENERAL OF NANOBATERIAL THERAPY
Microbes, their toxins or their shed components may contribute to pathological
calcifications in several ways. They may (1) damage cellular membranes, resulting
in exposure of tissue components capable of forming crystallizing nidi (Wiessner
et al ., 2001) or (2) alter local levels of calcium and phosphate
in tissue to saturating concentrations that in turn promote crystal formation
on available nidi; (3) the microbe may be calcified directly (Streckfuss
et al., 1974; Vogel and Smith, 1976; Van
Dijk et al ., 1998) or (4) microbial components may interact with
tissue components to form complexes that are hybrid nidi. NB or its fragments
may be nidi, but they are not necessarily the only nidi for the formation of
pathological calcifications (Garcia Cuerpo et al .,
2000). As microbial components are known to bind to apatite (Berry
and Siragusa, 1997), NB may also contribute directly to the primary pathogenesis
of disease by acting as a system for the delivery of microbial and other toxins
to tissues (Akerman et al., 1997; Kajander
et al., 2001), a process that would require endocytosis (Ciftcioglu
and Kajander, 1998). Future research is required to determine the classical
and potentially novel mechanism(s) by which drugs inhibit the growth of NB,
alter the morphology of NB and affect the genesis of diverse types of microbial
and tissue calcifications.
Dissolution of calcified shells of NB: The first step of the anti-nanobacteria phase is to weaken the calcified shells using substances like liquid zeolites and fulvic acid, which get in between the molecular bonds and thus compromise the shells structure. This is followed up by sessions with Ethylene-Diamine-Tetra-Acetic Acid (EDTA) and/or Dimethlyl Sulfoxide (DMSO) to further weaken that troublesome shell.
Chelation therapy: EDTA is chelating calcium, copper and iron, high
blood and tissue concentrations of which are suspected to promote atherogenesis
through oxidative stress. EDTA chelates and removes via urine other poisonous
heavy metals which may promote atherogenesis. Interestingly, very high-dose
(3 g day-1) oral EDTA or subcutaneous EDTA-magnesium therapy have
been reported to reduce cholesterol content in hypercholesterolemic rabbits
(Uhl et al., 1992; Evans
et al., 2001). Lipid modulating effects of EDTA are also supported
by the present findings: comet therapy improved blood lipid patterns in Coronary
Artery Disease (CAD) patients even under statin therapy. Increased activity
of matrix metalloproteinases has been implicated in atherosclerosis in several
ways. Metalloproteinase activity is dependent on zinc and calcium ions (Sierevogel
et al., 2003). Both tetracycline and EDTA inhibit matrix metalloproteinases.
EDTA and tetracycline also inhibit oxidative enzymes and act as antioxidants,
even reducing experimental ischemic and reperfusion lesion sizes. EDTA has strong
inhibitory action on blood clotting. EDTA may inhibit many calcium-mediated
signaling pathways directly or indirectly via changes in the concentration of
extracellular ionized calcium affecting function of calcium channels in cell
membrane. One such target is immunological activation, another is smooth muscle
contraction, both of importance, e.g., in coronary angina. All these action
mechanisms could be pharmacologically important in atherosclerosis. Novel rectal
administration of EDTA has been shown to result in high blood EDTA levels sustained
for a long time. Furthermore, the contributory effects of the oral powder component
should be evaluated. It contained several antioxidants, vitamins, amino acids
among other agents. Further studies are needed to delineate its actions and
Drug therapy: Carson (1998) studied on the
effects of drugs on the growth and morphology of NB within the larger context
of microbes as provocateurs of soft tissue calcifications, lesions that occur
in a surprisingly wide array of important diseases. He found that when drugs
altered the morphology of NB, there was a loss of (1) electron density, (2)
coccobacillary shape and (3) defined borders. Exceptions were enlarged NB observed
with nitrofurantoin and the amorphous debris and paucity of residual NB observed
with inhibitory concentrations of tetracycline and ampicillin. The relatedness,
if any, of the findings for this test system for the detection of inhibition
of NB to the reported drug-induced effects on the viability and morphology of
classical bacteria and fungi is yet to be determined (Davis
et al., 1997; Mintz and Fives-Taylor, 2000;
Yokochi et al., 2000). Regarding the test system
for detection of the inhibition of NB described here, our earlier investigations
showed that NB reach the log period of multiplication within a month if the
A650 of the initial inoculum density was lower than 20 (turbidity equivalent
to that of a 0.5 McFarland standard). The inoculum density of the NB used in
this inhibitory test allowed us to obtain logarithmic growth over the 14-day
test period. Previous work also demonstrated that the absorbance of NB grown
in the presence of Fetal Bovine Serum (FBS) is due to an increase in the number
of NB and not an increase in the mass of each NB particle (Ciftcioglu
and Kajander, 1999). In the present study, Transmission Electron Microscopy
(TEM) of the negative control showed no evidence of protein precipitation or
classical crystal formation (Miller, 1998), thus discounting
these factors as being responsible for the changes in absorbance. Furthermore,
if protein precipitation had occurred, an increase in absorbance of the negative
control (Dulbeccos modified Eagles medium (DMEM) plus 10% gamma-irradiated
FBS) should have occurred.
Use of absorbance to monitor the growth of NB is preferred because NB can exhibit
clumping, making particle counting by flow cytometry unreliable and scanning
electron microscopy SEM laborious. In this study, NB was inhibited in vitro
at clinically achievable levels in serum and urine (Garrison,
2000) by ampicillin, trimethoprim, trimethoprim-sulfamethoxazole, nitrofurantoin
(a urinary antiseptic) and tetracycline HCl. It is commonly known that ampicillin
inhibits bacterial cell wall synthesis, but like some other penicillins, it
is also a calcium chelator (Crossland, 1970). The inhibition
by ampicillin may also have been influenced by the lack of detectable β-lactamase
in NB and the somewhat zwitterionic nature of ampicillin that enables it to
penetrate the cell walls of gram-negative bacteria (Livermore
and Williams, 1996). Trimethoprim, trimethoprim-sulfamethoxazole and nitrofurantoin
are reported to inhibit protein and DNA syntheses; we did not find reports of
calcium chelation activities for these drugs.
Tetracycline is reported to inhibit bacterial protein synthesis, chelate calcium
and inhibit metalloproteinases, a property of potential use in the treatment
of osteoarthritis, periodontitis and cancer (Hartzen et
al., 1997). Tetracycline is already used in the treatment of some periodontal
diseases and dental stone formation (Ryan et al.,
NB have been isolated from human dental stones (Ciftcioglu
et al., 1998). There was a difference in the in vitro activity
of tetracycline HCl (MIC, 1.95 μg mL-1) and that of doxycycline
(MIC, 62.5 μg mL-1) against NB. Although doxycycline is more
highly protein bound and approximately 10 times more lipophilic than tetracycline
HCl (Cunha et al., 1982), their activities against
NB observed in vitro correlated with their comparative levels of calcium
binding. The level of chelation of tetracycline to calcium (40%) is reported
to be twice that for doxycycline (19%) (Von Wittenau, 1968).
The aminoglycosides are primarily known as inhibitors of protein synthesis but
more recently it has been recognized that they displace cell biofilm-associated
calcium and magnesium that link polysaccharides of lipopolysaccharide molecules
(Peterson et al., 1985). Gentamicin, kanamycin
and neomycin did not block the multiplication of NB. However, gentamicin caused
a reduction in the amount of putative biofilm surrounding NB.
NB are positive by the differential Limulus amoebocyte lysate assay
(Hjelle et al., 2000) but the lipopolysaccharide
of NB has not been sufficiently characterized to allow further speculation regarding
the observed lack of activity of these antibiotics.
IN VITRO INHIBITION OF NB BY ANTIMICROBIAL DRUGS
Ciftcioglu et al. (2002) tested 16 classes
of antimicrobial drugs for their abilities to inhibit the in vitro multiplication
of NB, found in human kidney stones and kidney cyst fluids from patients with
Polycystic Kidney Disease (PKD). They describe a modified microdilution inhibitory
test that accommodates the unique growth conditions and long multiplication
times of NB for 14 days in cell culture medium. Bactericidal or bacteriostatic
drug effects were distinguished by subsequent subculture in drug-free media
and monitoring for increasing absorbance. NB isolated from Fetal Bovine Serum
(FBS) were inhibited by tetracycline HCl, nitrofurantoin, trimethoprim, trimethoprim-sulfamethoxazole
and ampicillin at levels achievable in serum and urine; all drugs except ampicillin
were cidal. Tetracycline also inhibited multiplication of isolates of NB from
human kidney stones and kidney cyst fluids from patients with PKD. The other
antibiotics tested against FBS-derived NB either had no effect or exhibited
an inhibitory concentration above clinically achievable levels; the aminoglycosides
and vancomycin were bacteriostatic. Antibiotic-induced morphological changes
to NB were observed by electron microscopy. Bisphosphonates, aminocaproic acid,
potassium citrate-citric acid solutions and 5-fluorouracil also inhibited the
multiplication of NB in a cidal manner.
It is not clear that inhibition of the growth of NB requires chelation. Calcium
binding may contribute to the effects against NB of the potassium citrate and
citric acid mixture (Hjelle et al., 2000) and
some of the antimicrobics and other drugs tested. However, the nonchelators
nitrofurantoin, 5- fluorouracil and aminocaproic acid were active against NB.
Conversely, ciprofloxacin, a known chelator, was not active. The classical mechanisms
of action of these drugs against NB would be consistent with reports that NB
contain protein, DNA, apatite and muramic acid (Kajander
et al., 1994) and are positive for endotoxin by the differential
Limulus amoebocyte lysate assay and by immunoblotting. Of course, drugs
effective against NB in vitro may act via nonclassical mechanisms. New
mechanisms of antibiotic action are increasingly appearing in the literature,
such as (1) gentamicins effect on ribosomes to correct the enzyme deficiency
that causes Hurlers syndrome in cultured fibroblasts from patients (Kajander
et al., 1994) and (2) the discovery that a genetically engineered
live-attenuated human immunodeficiency virus will reproduce only in the presence
of doxycycline (Verhoef et al., 2001).
NB are sensitive in vitro to tetracycline and its action is increased
by EDTA dissolving NB apatitic protective coat (Ciftcioglu
et al., 2002). Thus, combination of these drugs might offer a novel
treatment for calcific atherosclerotic disease. The present trial treatment
regimen also included oral powder containing EDTA plus amino acids, vitamins
and proteins to support the EDTA-tetracycline therapy and to elicit beneficial
effects on known risk factors for heart disease.
Shoskes et al. (2005) developed a treatment
to eradicate calcification formed by NB in the etiology and symptoms of Category
III chronic prostatitis/Chronic Pelvic Pain Syndrome (CPPS). It consists of
an antibiotic (tetracycline), a nutraceutical that purportedly allows the antibiotic
to penetrate the stone and a suppository containing EDTA to dissolve the stone.
Although, this therapy warrants further study for the placebo effect and to
explore the role of nanobacterial infection as a cause of prostatic stones and
the role of prostatic stones.
HERBAL MEDICINE IN TREATMENT OF NB
Hadjzadeh et al. (2007) stated that ethanolic
extract of Nigella sativa seeds had a preventive effect on (calcium oxalate)
CaOx calculus formation in the kidney of rats due to ethylene glycol consumption.
The ethanolic extract also decreased the number of CaOx calculi in the treated
group by 57%. Aglichon and flavonoids (qurecetin and kaempferol) which are present
in black seeds have strong antioxidant and scavenging effects; thus, it may
be suggested that the preventive and disruptive effects of black seeds on CaOx
calculi are attributed to these mechanisms (Comalada et
al., 2006). It has been reported that CaOx calculi such as struvite
calculi may have a bacterial origin such as NB (Kramer
et al., 2000). Black seeds also have antibacterial effects and therefore,
may be effective in this mechanism of CaOx calculus formation (Hanafy
and Hatem, 1991).
Various researchers have shown that garlic extracts exhibit a wide spectrum
of antibacterial activity against gram-negative and gram-positive bacteria including
species of Escherichia, Salmonella, Staphylococcus,
Streptococcus, Klebsiella, Proteus, Bacillus and
Clostridium. Even acid-fast bacteria such as Mycobacterium tuberculosis
are sensitive to garlic. Research shows that garlic extracts are effective
against Helicobacter pylori, the cause of gastric ulcers. Garlic extracts
can also prevent the formation of Staphylococcus enterotoxins A, B
and C1 and also thermonuclease. Researchers Cavallito
and Bailey (1944) were the first to demonstrate that the antibacterial action
of garlic is mainly due to allicin. Interestingly, allicin has also been proven
to be effective against various bacterial strains resistant to antibiotics such
as Methicillin Resistant Staphylococcus Aureus (MRSA) as well as other multi-drug-resistant
enterotoxicogenic strains of Escherichia coli, Enterococcus,
Shigella dysenteriae, S. flexneni and S. sonnei cells (Hughes
and Lawson, 1991; Yamada and Azuma, 1997).
TREATMENT OF UROLITHIASIS (KIDNEY STONES)
The relationship between urinary infections and stone formation has been recognized
since ancient times and it has been over a century since bacterial degradation
of urea was postulated to cause stones. Specific therapy for urease-producing
bacteria, such as urease-inhibitors and antibiotics, has allowed for treatment
for this subset of urinary stones. Future directions for research include development
of novel urease-inhibitors and chemicals to enhance the protective glycosaminoglycan
layer. An improved understanding of the pathogenesis of calcium-based stones
has led to the discovery of potential roles for nanobacteria and Oxalobacter
formingenes (Rahman et al., 2003).
The use of catheters, both urethral and ureteral, is common in the urinary tract and is associated with significant morbidity, primarily from associated infections. Catheters to prevent bacterial colonization and formation of biofilms have been created using various coatings, including ciprofloxacin, hydrogel and silver. Use of these types of catheters may minimize infections and encrustation inherent with their placement in the urinary tract.
TREATMENT OF PROSTATITIS
The standard treatment for chronic bacterial prostatitis involves a 1-3 months
course of prostate-penetrating antibiotics such as fluoroquinolones, trimethoprim-sulfamethoxazole
(Septra), or trimethoprim (Protoprim). The cure rate is 60-80% with fluoroquinolones
and about 30-50% with Septra and Protoprim. Overall, it is estimated that about
one-third of category II patients have recurrences after a seemingly successful
first treatment. It is not clear why this is but there is some speculation that
stones (calculi) and other debris lodged in the ducts of the prostate may prevent
the antibiotics from reaching and completely eliminating the infectious bacteria
(Nickel et al., 1999). It is also recommended
that additional tests (ultrasound, CT scans, MRI) be performed in order to determine
if an underlying cause can be found and eliminated (Habermacher,
It is very important to supplement with live probiotics (L. acidophilus,
L. bifidus, L. casei, etc.) during and for a couple of months after
treatment with antibiotics, especially the broad-spectrum ones like fluoroquinolones.
These antibiotics destroy the normal flora in the gut (large intestine) and
their use can result in a nasty case of candidiasis which can be very difficult
to eradicate (Murray and Pizzorno, 1998).
HERBAL TREATMENT FOR PROSTATITIS
Quercetin is a naturally occurring bioflavonoid found in green tea, onions
and red wine. It has documented anti-inflammatory, antioxidant and nitric oxide-inhibiting
properties. Several studies have shown it to be effective in the treatment of
chronic prostatitis. Quercetin was particularly effective in reducing pain and
improving quality-of-life score (Shoskes et al.,
Cernilton or cernitin is bee pollen gathered from the rye flower. At least
two clinical trials have found it to be effective in alleviating CPPS symptoms.
Buck et al. (1989) reported that patients with
CPPS experienced complete and lasting relief or a marked improvement after supplementing
with cernilton. Rugendorff et al. (1993) reported
that cernilton also was effective in alleviating symptoms of BPH like urethral
strictures, prostatic calculi (stones) or bladder neck sclerosis.
Saw palmetto is being used successfully in the treatment of Benign Prostatic
Hyperplasia (BPH) (Gordon and Shaughnessy, 2003). However,
there are no clinical trials indicating that it is effective in the treatment
of CPPS. As a matter of fact, one trial comparing finasteride and saw palmetto
in the treatment of CPPS found no beneficial effect of saw palmetto (Yang
and Te, 2005).
Small-flowered willow herb (Epilobium parviflorum) is a well known folk
remedy for the treatment of prostate problems, including BPH and prostatitis.
Steenkamp et al. (2006) found that Epilobium,
both as a tea and ethanol extract was highly effective in inhibiting the growth
of E. coli in culture; the ethanol extract was substantially more effective
than the water extract (tea). The ethanol extract of Epilobium was also
very effective as both a COX-1 and COX-2 inhibitor in culture experiments and
showed significant antioxidant activity.
Waterhouse (2007) suggested triple protocol for treatment-resistant
cell wall deficient bacteria (NB) involves immune modulation, which consists
of vitamin D reduction and higher than usual dosages of the angiotensin II receptor
blocker, olmesartan. These two components of the protocol enable the immune
system to kill the NB weakened by the third component is very low dosages of
NEW TRENDS FOR ERADICATION OF NANOBACTERIA WITH PHOTOMEDICINE
Sommer et al. (2003) evaluated the effect of
various wavelengths of light on Nanobacteria (NB). The results indicated that
suitable wavelengths of light could be instrumental in elevating the vitality
level of NB, preventing the production of NB-mediated slime and simultaneously
increasing the vitality level of mitochondria. This finding could stimulate
the design of cooperative therapy concepts that could reduce death caused by
Sommer (2007) identified the synergistic effects in
the interaction of light with biosystems in the presence of chemical agents.
Their systematic analysis promises therapeutic strategies. He concluded that
Low-Level Light (LLL) therapy is compatible with antiinfectives and even capable
of enhancing effects of superficially applied and/or absorbed antiinfectives.
Temporal coordination between light treatment and drug administration maximizes
drug effects and minimizes possible adverse effects. Furthermore, irradiation
should start when the drug concentration has reached its maximum in the desired
field of action. Light-induced flow in nanoscale cavities could represent one
mechanism of LLL therapy.
PROMISING OPTICAL NANOPARTICLES THERAPY
Sereemaspun et al. (2008) determined the in
vitro effect of gold and silver nanoparticles as the two most frequently
used metallic nanomaterials for therapeutics and diagnostic on the microsomes
containing wild-type cDNA expressed human CYP450 enzymes CYP1A2, 2C9, 2C19 and
3A4. Results demonstrated that all of the CYP450s activities were down-regulated
by metallic nanoparticles.
Lukhele et al. (2010) explored the use of nano-sized
materials for the removal of bacteria in water using silver nanoparticles immobilized
onto carbon nanotube and cyclodextrin polymers.
Sap-Iam et al. (2010) suggested that the silver
nanoparticles synthesized by UV-irradiation can be employed in biocontrol of
Gilaki (2010) stimulated investigational progressions
for biosynthesis of silver nanometals using plant leaf extracts.
Semwal et al. (2010) developed novel and efficacious
nanoparticles for drug delivery as a promising progress in cancer nanotechnology.
The release characteristic of drugs from these polymeric systems is dependent
on the drug loading contents and chain length of the hydrophobic/hydrophilic
part of the copolymers.
Warisnoicharoen et al. (2011) used silver nanoparticles
have been recently for a wide range of applications including health and household
products even though an understanding of their mechanistic action in human.
This study was funded by Cairo University, Project No, 3/5 2009 Application
of nanobacteria in the new millennium.
Akerman, K.K., J.T. Kuikka, N. Ciftcioglu, J. Parkkinen, K.A. Bergstroem,
I. Kuronen and E.O. Kajander, 1997. Radiolabeling and
in vivo distribution of nanobacteria in rabbit. Proc. SPIE Int. Soc.
Opt. Eng., 3111: 436-442.
Berry, E.D. and G.R. Siragusa, 1997. Hydroxyapatite adherence
as a means to concentrate bacteria. Applied
Environ. Microbiol., 63: 4069-4074
Bock, E., V. Calugi, V. Stolfi, P. Rossi, R. D’Ascenzo and F.M. Solivetti,
1989. Calcifications of the prostate: A transrectal echographic
Med., 77: 501-503
Bratos-Perez, M.A., P.L. Sanchez, S. Garcia de Cruz, E. Villacorta and I.F.
Palacios et al., 2008. Association between self-replicating
calcifying nanoparticles and aortic stenosis: A possible link to valve calcification.
J., 29: 371-376
Buck, A.C., R.W. Rees and L. Ebeling, 1989. Treatment
of chronic prostatitis and prostatodynia with pollen extract. Br.
J. Urol., 64: 496-499
Carson, D.A., 1998. An infectious origin of extraskeletal
Natl. Acad. Sci. USA., 95: 7846-4747
Cassell, G.H., 1998. Infectious causes of chronic inflammatory
diseases and cancer. Emerg.
Infect. Dis., 4: 475-487
Cavallito, C.J. and J.H. Bailey, 1994. Allicin, the antibacterial
principle of Allium sativum. I. Isolation, physical properties and antibacterial
action. J. Am.
Chem. Soc., 66: 1950-1951
Ciftcioglu, N. and E.O. Kajander, 1998. Interaction of
nanobacteria with cultured mammalian cells. Pathophysiology,
Ciftcioglu, N. and E.O. Kajander, 1999. Growth factors
for nanobacteria. Proc. SPIE Int. Soc. Opt. Eng., 3755: 113-119.
Ciftcioglu, N., D.S. McKay and E.O. Kajander, 2003. Association
between nanobacteria and periodontal disease. Circulation,
Ciftcioglu, N., M. Bjorklund, K. Kuorikoski, K. Bergstrom and E.O. Kajander,
1999. Nanobacteria: An infectious cause for kidney stone
Int., 56: 1893-1898
Ciftcioglu, N., M.A. Miller-Hjelle, J.T. Hjelle and E.O. Kajander, 2002. Inhibition
of nanobacteria by antimicrobial drugs as measured by a modified microdilution
Agents Chemother., 46: 2077-2086
Ciftcioglu, N., V. Ciftcioglu, H. Vali, E. Turcott and E.O. Kajander, 1998.
Sedimentary rocks in our mouth: Dental pulp stones made
by nanobacteria. Proc. SPIE Int. Soc. Opt. Eng., 3441: 130-135.
Comalada, M., I. Ballester, E. Bailon, J. Galvez, F.S. de Medina and A. Zarzuelo,
2006. Inhibition of pro-inflammatory markers in primary
bone marrow-derived mouse macrophages by naturally occurring flavonoids: Analysis
of the structure-activity relationship. Biochem.
Pharmacol., 72: 1010-1021
Crossland, J., 1970. Lewis Pharmacology. 4th Edn., Livingstone,
London, UK., pp: 1124-1125.
Cunha, B.A., C.M. Sibley and A.M. Ristuccia, 1982. Doxycycline.
Monit., 4: 115-135
Davis, K.J., P. Vogel, D.L. Fritz, K.E. Steele and M.L. Pitt et al.,
1997. Bacterial filamentation of Yersinia pestis
by β-lactam antibiotics in experimentally infected mice. Arch.
Pathol. Lab. Med., 121: 865-868
Demir, T., 2008. Is there any relation of nanobacteria
with periodontal diseases. Med.
Hypotheses, 70: 36-39
Evans, D.A.P., M. Tariq, B. Sujata, G. McCann and S. Sobki, 2001. The
effects of magnesium sulphate and EDTA in the hypercholesterolaemic rabbit.
Obes. Metab., 3: 417-422
Garcia Cuerpo, E., E. Olavi Kajander, N. Ciftcioglu, F. Lovaco Castellano and
C. Correa et al., 2000. Nanobacteria: An experimental
neo-lithogenesis model. Arch.
Esp. Urol., 53: 291-303, (Article in Spanish)
Garrison, J., 2000. Optimal properties of agents used
to treat acute, uncomplicated urinary tract infections. Drug
Ther. Topics, 29: 23-28
Geramoutsos, I., K. Gyftopoulos, P. Perimenis, V. Thanou, D. Liagka, D. Siamblis
and G. Barbalias, 2004. Clinical correlation of prostatic
lithiasis with chronic pelvic pain syndromes in young adults. Eur.
Urol., 45: 333-338
Gilaki, M., 2010. Biosynthesis of silver nanoparticles
using plant extracts. J.
Biol. Sci., 10: 465-467
Gordon, A.E. and A.F. Shaughnessy, 2003. Saw palmetto
for prostate disorders. Am.
Fam. Physician, 67: 1281-1283
Habermacher, G.M., J.T. Chason and A.J. Schaeffer, 2006. Prostatitis/chronic
pelvic pain syndrome. Annu.
Rev. Med., 57: 195-206
Hadjzadeh, M.A., A. Khoei, Z. Hadjzadeh and M. Parizady, 2007. Ethanolic
extract of Nigella sativa L. seeds on ethylene glycol-induced kidney
calculi in rats. Urol.
J., 4: 86-90
Hanafy, M.S.M. and M.E. Hatem, 1991. Studies on the antimicrobial
activity of Nigella sativa seed (black cumin). J.
Ethnopharmacol., 34: 275-278
Hartzen, S.H., L.P. Andersen, A. Bremmelgaard, H. Colding and M. Arpi et
al., 1997. Antimicrobial susceptibility of testing
of 230 Helicobacter pylori strains: Importance of medium, inoculum and
incubation time. Antimicrob.
Agents Chemother., 41: 2634-2639
Hjelle, J.T., M.A. Miller-Hjelle, I.R. Poxton, E.O. Kajander and N. Ciftcioglu
et al., 2000. Endotoxin and nanobacteria in polycystic
kidney disease. Kidney
Int., 57: 2360-2374
Hudelist, G., C.F. Singer, E. Kubista, M. Manavi, R. Mueller, K. Pischinger
and K. Czerwenka, 2004. Presence of nanobacteria in psammoma
bodies of ovarian cancer: Evidence for pathogenetic role in intratumoral biomineralization.
Hughes, B.G. and L.D. Lawson, 1991. Antimicrobial effects
of Allium sativum L. (garlic), Allium ampeloprasum (elephant garlic)
and Allium cepa (onion), garlic compounds and commercial garlic supplement
products. Phytother. Res., 5: 154-158.
Jelic, T.M., H.H. Chang, R. Roque, A.M. Malas, S.G. Warren and A.P. Sommer,
2007. Nanobacteria-associated calcific aortic valve stenosis.
Valve Dis., 16: 101-105
Kajander, E.O. and N. Ciftcioglu, 1998. Nanobacteria:
An alternative mechanism for pathogenic intra and extra cellular calcification
and stone formation. Proc.
Natl. Sci. USA., 95: 8274-8279
Kajander, E.O., E. Tahvanien, I. Kuronen and N. Ciftcioglu, 1994. Comparison
of staphylococci and novel bacteria-like particles from blood. Zbl. Bakt. Suppl.,
Kajander, E.O., I. Kuronen, K. Akerman, A. Pelttari and N. Ciftcioglu, 1997.
Nanobacteria from blood, the smallest culturable autonomously
replicating agent on earth. Proc. SPIE, 3111: 420-428.
Kajander, E.O., N. Ciftcioglu, K. Aho and E. Garcia-Cuerpo, 2003. Characteristics
of nanobacteria and their possible role in stone formation. Urol.
Res., 31: 47-54
Kajander, E.O., N. Ciftcioglu, M.A. Miller-Hjelle and J.T. Hjelle, 2001. Nanobacteria:
Controversial pathogens in nephrolithiasis and polycystic kidney disease. Curr.
Opin. Nephrol. Hypertens., 10: 445-452
Kramer, G., H.C. Klingler and G.E. Steiner, 2000. Role
of bacteria in the development of kidney stones. Curr.
Opin. Urol., 10: 35-38
Livermore, D. and J.D. Williams, 1996. β-Lactams:
Mode of Action and Mechanisms of Bacterial Resistance. In: Antibiotics in Laboratory
Medicine, Lorian, V. (Ed.). The William and Wilkins Co., Baltimore, USA., pp:
Lukhele, L.P., B.B. Mamba, M.N.B. Momba and R.W.M. Krause, 2010. Water
disinfection using novel cyclodextrin polyurethanes containing silver nanoparticles
supported on carbon nanotubes. J.
Applied Sciences, 10: 65-70
Miller, P.D., 1998. Efficacy and safety of cyclical etidronate
therapy in the long-term treatment of osteoporosis. Rev. Contemp. Pharmacother.,
Mintz, K.P. and P.M. Fives-Taylor, 2000. impA, a gene
coding for an inner membrane protein, influences colonial morphology of Actinobacillus
Immun., 68: 6580-6586
Murray, M.T. and J.E. Pizzorno, 1998. Encyclopedia of Natural
Medicine. 2nd Rev. Edn., Prima Publishing, Rocklin, CA, pp: 300-302.
Nickel, J.C., J. Downey, A.E. Feliciano Jr. and B. Hennenfent, 1999. Repetitive
prostatic massage therapy for chronic refractory prostatitis: The Philippine
Urol., 5: 146-151
Peterson, A., R.E. Hancock and E.J. McGroarty, 1985. Binding
of polycationic antibiotics and polyamines to lipopolysaccharide of Pseudomonas
Bacteriol., 164: 1256-1261
Rahman, N.U., M.V. Meng and M.L. Stoller, 2003. Infections
and urinary stone disease. Curr.
Pharm. Des., 9: 975-981
Rugendorff, E.W., W. Weidner, L. Ebeling and A.C. Buck, 1993. Results
of treatment with pollen extract (Cernilton N) in chronic prostatitis and prostatodynia.
Urol., 71: 433-438
Ryan, M.E., S. Ramamurthy and L.M. Golub, 1996. Matrix
metalloproteinases and their inhibition in periodontal treatment. Curr.
Opin. Periodontol., 3: 85-96
Sap-Iam, N., C. Homklinchan, R. Larpudomlert, W. Warisnoicharoen, A. Sereemaspun
and S.T. Dubas, 2010. UV irradiation-induced silver nanoparticles
as mosquito larvicides. J.
Applied Sci., 10: 3132-3136
Semwal, R., D.K. Semwal, R. Badoni, S. Gupta and A.K. Madan, 2010. Targeted
drug nanoparticles: An emphasis on self-assembled polymeric system. J.
Med. Sci., 10: 130-137
Sereemaspun, A., P. Hongpiticharoen, R. Rojanathanes, P. Maneewattanapinyo,
S. Ekgasit and W. Warisnoicharoen, 2008. Inhibition of
human cytochrome P450 enzymes by metallic nanoparticles: A preliminary to nanogenomics.
Pharmacol., 4: 492-495
Shoskes, D.A., K.D. Thomas and E. Gomez, 2005. Anti-nanobacterial
therapy for men with chronic prostatitis/chronic pelvic pain syndrome and prostatic
stones: Preliminary experience. J.
Urol., 173: 474-477
Shoskes, D.A., S.I. Zeitlin, A. Shahed and J. Rajfer, 1999. Quercetin
in men with category III chronic prostatitis: A preliminary prospective, double-blind,
placebo-controlled trial. Urology,
Sierevogel, M.J., G. Pasterkamp, D.P.V. de Kleijn and B. Strauss, 2003. Matrix
metalloproteinases: A therapeutic target in cardiovascular disease. Curr.
Pharm. Design, 9: 1033-1040
Sommer, A.P., 2007. Antiinfectives and low-level light:
A new chapter in photomedicine. Photomed.
Laser Surg., 25: 150-158
Sommer, A.P., U. Oron, A.M. Pretorius, D.S. McKay and N. Ciftcioglu et al.,
2003. A preliminary investigation into light-modulated
replication of nanobacteria and heart disease. J.
Clin. Laser Med. Surg., 21: 231-235
Steenkamp, V., M.C. Gouws, M. Gulumian, E.E. Elgorashi and J. van Standen, 2006.
Studies on antibacterial, anti-inflammatory and antioxidant
activity of herbal remedies used in the treatment of benign prostatic hyperplasia
and prostatitis. J.
Ethnopharmacol., 103: 71-75
Streckfuss, J.L., W.N. Smith, L.R. Brown and M.M. Campbell, 1974. Calcification
of selected strains of Streptococcus mutans and Streptococcus sanguis.
Bacteriol., 120: 502-506
Uhl, H.S.M., R.C. Dysko, R.W. St Clair, 1992. EDTA reduces
liver cholesterol content in cholesterol-fed rabbits. Atherosclerosis,
Van Dijk, S., D.D. Dean, Y. Liu, Y. Zhao, J.M. Chirgwin, Z. Schwartz and B.D.
Boyan, 1998. Purification, amino acid sequence and cDNA
sequence of a novel calcium-precipitating proteolipids involved in calcification
of Corynebacterium matruchotii. Calcif.
Tissue Int., 62: 350-358
Verhoef, K., G. Marzio, W. Hillen, H. Bujard and B. Berkhout, 2001. Strict
control of human immunodeficiency virus type 1 replication by a genetic switch:
Tet for tat. J.
Virol., 75: 979-987
Vogel, J.J. and W.N. Smith, 1976. Calcification of membranes
isolated from Bacterionema matruchotii. J.
Dent. Res., 55: 1080-1083
Von Wittenau, M.S., 1968. Some pharmacokinetic aspects
of doxycycline metabolism in man. Chemotherapy,
Warisnoicharoen, W., P. Hongpiticharoen and S. Lawanprasert, 2011. Alteration
in enzymatic function of human cytochrome P450 by silver nanoparticles. Res.
J. Environ. Toxicol., 5: 58-64
Waterhouse, J.C., 2007. The Marshall Protocol for Lyme
disease and other chronic inflammatory conditions: Part one. Overview and implementation.
Townsend Lett., 285: 85-92.
Wen, Y., Y.G. Li, Z.L. Yang, X.J. Wang and H. Wei et al., 2005. Detection
of nanobacteria in serum, bile and gallbladder mucosa of patients with cholecystolithiasis.
Med. J. (Engl)., 118: 421-424
Wiessner, J.H., A.T. Hasegawa, L.Y. Hung, G.S. Mandel and N.S. Mandel, 2001.
Mechanisms of calcium oxalate crystal attachment to injured
renal collecting duct cells. Kidney
Int., 59: 637-644
Yamada, Y. and K. Azuma, 1997. Evaluation of the in
vitro antifungal activity of allicin. Antimicrob.
Agents Chemother., 11: 743-749
Yang, J. and A.E. Te, 2005. Saw palmetto and finasteride
in the treatment of category-III prostatitis/chronic pelvic pain syndrome. Curr.
Urol. Rep., 6: 290-295
Yokochi, T., K. Narita, A. Morikawa, K. Takahashi and Y. Kato et al.,
2000. Morphological change in Pseudomonas aeruginosa
following antibiotic treatment of experimental infection in mice and its relation
to susceptibility to phagocytosis and to release of endotoxin. Antimicrob.
Agents Chemother., 44: 205-206