High Iodine Concentration Attenuates RET/PTC3 Oncogene Activation in Thyroid Follicular Cells

Background: Papillary thyroid carcinoma (PTC) is frequently associated with a RET gene rearrangement that generates a RET/PTC oncogene. RET/PTC is a fusion of the tyrosine kinase domain of RET to the 50 portion of a different gene. This fusion results in a constitutively active MAPK pathway, which plays a key role in PTC development. The RET/PTC3 fusion is primarily associated with radiation-related PTC. Epidemiological studies show a lower incidence of PTC in radiation-exposed regions that are associated with an iodine-rich diet. Since the influence of excess iodine on the development of thyroid cancer is still unclear, the aim of this study is to evaluate the effect of high iodine concentrations on RET/PTC3-activated thyroid cells. Methods: PTC3-5 cells, a rat thyroid cell lineage harboring doxycycline-inducible RET/PTC3, were treated with 10(-3) M NaI. Cell growth was analyzed by cell counting and the MTT assay. The expression and phosphorylation state of MAPK pathway-related (Braf, Erk, pErk, and pRet) and thyroid-specific (natrium-iodide symporter [Nis] and thyroid-stimulating hormone receptor [Tshr]) proteins were analyzed by Western blotting. Thyroid-specific gene expression was further analyzed by quantitative reverse transcription (RT)-polymerase chain reaction. Results: A significant inhibition of proliferation was observed, along with no significant variation in cell death rate, in the iodine-treated cells. Further, iodine treatment attenuated the loss of Nis and Tshr gene and protein expression induced by RET/PTC3 oncogene induction. Finally, iodine treatment reduced Ret and Erk phosphorylation, without altering Braf and Erk expression. Conclusion: Our results indicate an antioncogenic role for excess iodine during thyroid oncogenic activation. These findings contribute to a better understanding of the effect of iodine on thyroid follicular cells, particularly how it may play a protective role during RET/PTC3 oncogene activation.

Hormone-regulated expression and distribution of versican in mouse uterine tissues

Background: Remodeling of the extracellular matrix is one of the most striking features observed in the uterus during the estrous cycle and after hormone replacement. Versican (VER) is a hyaluronan-binding proteoglycan that undergoes RNA alternative splicing, generating four distinct isoforms. This study analyzed the synthesis and distribution of VER in mouse uterine tissues during the estrous cycle, in ovariectomized (OVX) animals and after 17beta-estradiol (E2) and medroxyprogesterone (MPA) treatments, either alone or in combination. Methods: Uteri from mice in all phases of the estrous cycle, and animals subjected to ovariectomy and hormone replacement were collected for immunoperoxidase staining for versican, as well as PCR and quantitative Real Time PCR. Results: In diestrus and proestrus, VER was exclusively expressed in the endometrial stroma. In estrus and metaestrus, VER was present in both endometrial stroma and myometrium. In OVX mice, VER immunoreaction was abolished in all uterine tissues. VER expression was restored by E2, MPA and E2+MPA treatments. Real Time PCR analysis showed that VER expression increases considerably in the MPA-treated group. Analysis of mRNA identified isoforms V0, V1 and V3 in the mouse uterus. Conclusion: These results show that the expression of versican in uterine tissues is modulated by ovarian steroid hormones, in a tissue-specific manner. VER is induced in the myometrium exclusively by E2, whereas MPA induces VER deposition only in the endometrial stroma.

Effectiveness of 980-mm Diode and 1064-nm Extra-Long-Pulse Neodymium-Doped Yttrium Aluminum Garnet Lasers in Implant Disinfection

Objective: To evaluate the potential of 980-nm gallium aluminum arsenide (GaAlAs) and 1064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers to reduce bacteria after irradiation of implant surfaces contaminated with Enterococcus faecalis and Porphyromonas gingivalis and on irradiated implant surface morphology. Background: Despite the frequency of implant success, some implant loss is related to peri-implantitis because of difficulty in eliminating the biofilm. Methods: Implants (3.75 x 13 mm) with machined surfaces, surfaces sand blasted with titanium oxide (TiO(2)), and sand-blasted and acid-etched surfaces were exposed to P. gingivalis and E. faecalis cultures and irradiated with 980-nm GaAlAs or 1064-nm Nd: YAG lasers. After laser treatments, the number of remaining colony-forming units and implant surface morphology were analyzed using scanning electron microscopy (SEM). Results: The Nd: YAG laser was able to promote a total contamination reduction on all implants irradiated. The results with the GaAlAs laser showed 100% bacteria reduction on the implants irradiated with 3 W. Irradiation with 2.5 W and 3 W achieved 100% of bacteria reduction on P. gingivalis-contaminated implants. Decontamination was not complete for the sand-blasted TiO(2) (78.6%) and acid-etched surfaces (49.4%) contaminated with E. faecalis and irradiated with 2.5 W. SEM showed no implant surface changes. Conclusion: The wavelengths used in this research provided bacteria reduction without damaging implant surfaces. New clinical research should be encouraged for the use of this technology in the treatment of peri-implantitis.

Mycoplasma pneumoniae and/or Chlamydophila pneumoniae inoculation causing different aggravations in cholesterol-induced atherosclerosis in apoE KO male mice

Background: Chamydophila pneumoniae (CP) and/or Mycoplasma pneumoniae ( MP) are two bacteria detected in vulnerable atheromas. In this study we aimed to analyze whether CP and/or MP aggravates atherosclerosis induced by cholesterol-enriched diet in C57BL/6 apoE KO male mice. Thirty male apoE KO mice aged eight weeks fed by a diet containing 1% cholesterol until 32 weeks of age were divided into four groups: the first was inoculated with CP (n = 7), the second with MP (n = 12), the third with both CP + MP ( n = 5), and the fourth with saline (sham n = 6). The animals were re-inoculated at 36 weeks of age, and sacrificed at 40 weeks of age. Two ascending aorta and one aortic arch segments were sampled. In the most severely obstructed segment, vessel diameter, plaque height, percentage of luminal obstruction and the degree of adventitial inflammation were analyzed. The plaque area/intimal surface ratio was obtained by measuring all three segments. The adventitial inflammation was semiquantified (0 absent, 1 mild, 2 moderate, and 3 diffuse). Results: The mean and standard deviation of plaque height, % luminal obstruction, external diameter, the plaque area/intimal surface ratio and the adventitial inflammation values are the following for each group: MP (0.20 +/- 12 mm, 69 +/- 26%, 0.38 +/- 0.11 mm, 0.04 +/- 0.04 and 0.22 +/- 0.67), CP (0.23 +/- 0.08 mm, 90 +/- 26%, 0.37 +/- 0.08 mm, 0.04 +/- 0.03, and 0.44 +/- 0.53), MP + CP ( 18 +/- 0.08 mm, 84 +/- 4.0%, 0.35 +/- 0.25 mm, 0.03 +/- 0.03 and 1.33 +/- 0.82) and sham (0.08 +/- 0.09 mm, 42 +/- 46%, 0.30 +/- 0.10 mm, 0.02 +/- 0.03 and 0.71 +/- 0.76). A wider area of plaque/intimal surface was observed in MP + CP inoculated groups (p = 0.07 and 0.06) as well as an increased plaque height in CP (p = 0.01) in comparison with sham group. There was also an increased luminal obstruction (p = 0.047) in CP inoculated group in comparison to sham group. Adventitial inflammation in MP + CP inoculated group was higher than MP, CP and the sham groups (p = 0.02). Conclusion: Inoculation of CP, MP or both agents in C57BL/6 apoE KO male mice caused aggravation of experimental atherosclerosis induced by cholesterol-enriched diet, with distinct characteristics. CP inoculation increased the plaque height with positive vessel remodeling and co-inoculation of MP + CP caused the highest adventitial inflammation measures.

Genome Size, Karyotype Polymorphism and Chromosomal Evolution in Trypanosoma cruzi

Background: The Trypanosoma cruzi genome was sequenced from a hybrid strain (CL Brener). However, high allelic variation and the repetitive nature of the genome have prevented the complete linear sequence of chromosomes being determined. Determining the full complement of chromosomes and establishing syntenic groups will be important in defining the structure of T. cruzi chromosomes. A large amount of information is now available for T. cruzi and Trypanosoma brucei, providing the opportunity to compare and describe the overall patterns of chromosomal evolution in these parasites. Methodology/Principal Findings: The genome sizes, repetitive DNA contents, and the numbers and sizes of chromosomes of nine strains of T. cruzi from four lineages (TcI, TcII, TcV and TcVI) were determined. The genome of the TcI group was statistically smaller than other lineages, with the exception of the TcI isolate Tc1161 (Jose-IMT). Satellite DNA content was correlated with genome size for all isolates, but this was not accompanied by simultaneous amplification of retrotransposons. Regardless of chromosomal polymorphism, large syntenic groups are conserved among T. cruzi lineages. Duplicated chromosome-sized regions were identified and could be retained as paralogous loci, increasing the dosage of several genes. By comparing T. cruzi and T. brucei chromosomes, homologous chromosomal regions in T. brucei were identified. Chromosomes Tb9 and Tb11 of T. brucei share regions of syntenic homology with three and six T. cruzi chromosomal bands, respectively. Conclusions: Despite genome size variation and karyotype polymorphism, T. cruzi lineages exhibit conservation of chromosome structure. Several syntenic groups are conserved among all isolates analyzed in this study. The syntenic regions are larger than expected if rearrangements occur randomly, suggesting that they are conserved owing to positive selection. Mapping of the syntenic regions on T. cruzi chromosomal bands provides evidence for the occurrence of fusion and split events involving T. brucei and T. cruzi chromosomes.

Impaired Innate Immunity in Tlr4(-/-) Mice but Preserved CD8(+) T Cell Responses against Trypanosoma cruzi in Tlr4-, Tlr2-, Tlr9- or Myd88-Deficient Mice

The murine model of T. cruzi infection has provided compelling evidence that development of host resistance against intracellular protozoans critically depends on the activation of members of the Toll-like receptor (TLR) family via the MyD88 adaptor molecule. However, the possibility that TLR/MyD88 signaling pathways also control the induction of immunoprotective CD8(+) T cell-mediated effector functions has not been investigated to date. We addressed this question by measuring the frequencies of IFN-gamma secreting CD8(+) T cells specific for H-2K(b)-restricted immunodominant peptides as well as the in vivo Ag-specific cytotoxic response in infected animals that are deficient either in TLR2, TLR4, TLR9 or MyD88 signaling pathways. Strikingly, we found that T. cruzi-infected Tlr2(-/-), Tlr4(-/-), Tlr9(-/-) or Myd88(-/-) mice generated both specific cytotoxic responses and IFN-gamma secreting CD8(+) T cells at levels comparable to WT mice, although the frequency of IFN-gamma(+)CD4(+) cells was diminished in infected Myd88(-/-) mice. We also analyzed the efficiency of TLR4-driven immune responses against T. cruzi using TLR4-deficient mice on the C57BL genetic background (B6 and B10). Our studies demonstrated that TLR4 signaling is required for optimal production of IFN-gamma, TNF-alpha and nitric oxide (NO) in the spleen of infected animals and, as a consequence, Tlr4(-/-) mice display higher parasitemia levels. Collectively, our results indicate that TLR4, as well as previously shown for TLR2, TLR9 and MyD88, contributes to the innate immune response and, consequently, resistance in the acute phase of infection, although each of these pathways is not individually essential for the generation of class I-restricted responses against T. cruzi.

Actions of a Proline Analogue, L-Thiazolidine-4-Carboxylic Acid (T4C), on Trypanosoma cruzi

It is well established that L-proline has several roles in the biology of trypanosomatids. In Trypanosoma cruzi, the etiological agent of Chagas' disease, this amino acid is involved in energy metabolism, differentiation processes and resistance to osmotic stress. In this study, we analyzed the effects of interfering with L-proline metabolism on the viability and on other aspects of the T. cruzi life cycle using the proline analogue L- thiazolidine-4-carboxylic acid (T4C). The growth of epimastigotes was evaluated using different concentrations of T4C in standard culture conditions and at high temperature or acidic pH. We also evaluated possible interactions of this analogue with stress conditions such as those produced by nutrient starvation and oxidative stress. T4C showed a dose-response effect on epimastigote growth (IC(50) = 0.89+/-0.02 mM at 28 degrees C), and the inhibitory effect of this analogue was synergistic (p<0.05) with temperature (0.54+/-0.01 mM at 37 degrees C). T4C significantly diminished parasite survival (p<0.05) in combination with nutrient starvation and oxidative stress conditions. Pre-incubation of the parasites with L-proline resulted in a protective effect against oxidative stress, but this was not seen in the presence of the drug. Finally, the trypomastigote bursting from infected mammalian cells was evaluated and found to be inhibited by up to 56% when cells were treated with non-toxic concentrations of T4C (between 1 and 10 mM). All these data together suggest that T4C could be an interesting therapeutic drug if combined with others that affect, for example, oxidative stress. The data also support the participation of proline metabolism in the resistance to oxidative stress.

Tamoxifen Is Effective in the Treatment of Leishmania amazonensis Infections in Mice

Background: Chemotherapy is still a critical issue in the management of leishmaniasis. Until recently, pentavalent antimonials, amphotericin B or pentamidine compounded the classical arsenal of treatment. All these drugs are toxic and have to be administered by the parenteral route. Tamoxifen has been used as an antiestrogen in the treatment and prevention of breast cancer for many years. Its safety and pharmacological profiles are well established in humans. We have shown that tamoxifen is active as an antileishmanial compound in vitro, and in this paper we analyzed the efficacy of tamoxifen for the treatment of mice infected with Leishmania amazonensis, an etiological agent of localized cutaneous leishmaniasis and the main cause of diffuse cutaneous leishmaniasis in South America. Methodology/Principal Findings: BALB/c mice were infected with L. amazonensis promastigotes. Five weeks post-infection, treatment with 15 daily intraperitoneal injections of 20 mg/kg tamoxifen was administered. Lesion and ulcer sizes were recorded and parasite burden quantified by limiting dilution. A significant decrease in lesion size and ulcer development was noted in mice treated with tamoxifen as compared to control untreated animals. Parasite burden in the inoculation site at the end of treatment was reduced from 10(8.5 +/- 0.7) in control untreated animals to 10(5.0 +/- 0.0) in tamoxifen-treated mice. Parasite load was also reduced in the draining lymph nodes. The reduction in parasite number was sustained: 6 weeks after the end of treatment, 10(15.5 +/- 0.5) parasites were quantified from untreated animals, as opposed to 10(5.1 +/- 0.1) parasites detected in treated mice. Conclusions/Significance: Treatment of BALB/c mice infected with L. amazonensis for 15 days with tamoxifen resulted in significant decrease in lesion size and parasite burden. BALB/c mice infected with L. amazonensis represents a model of extreme susceptibility, and the striking and sustained reduction in the number of parasites in treated animals supports the proposal of further testing of this drug in other models of leishmaniasis.

Induction of mitotic crossing-over in diploid strains of Aspergillus nidulans using low-dose X-rays

As a contribution towards detecting the genetic effects of low doses of genotoxic physical agents, this paper deals with the consequences of low-dose X-rays in the Aspergillus nidulans genome. The irradiation doses studied were those commonly used in dental clinics (1-5 cGy). Even very low doses promoted increased mitotic crossing-over frequencies in diploid strains heterozygous for several genetic markers including the ones involved in DNA repair and recombination mechanisms. Genetic markers of several heterozygous strains were individu`ally analyzed disclosing that some markers were especially sensitive to the treatments. These markers should be chosen as bio-indicators in the homozygotization index assay to better detect the recombinogenic/carcinogenic genomic effects of low-dose X-rays.

Hepatitis B Infection Is Associated with Asymptomatic Malaria in the Brazilian Amazon

Background: Areas that are endemic for malaria are also highly endemic for hepatitis B virus (HBV) infection. Nevertheless, it is unknown whether HBV infection modifies the clinical presentation of malaria. This study aimed to address this question. Methodology and Findings: An observational study of 636 individuals was performed in Rondonia, western Amazon, Brazil between 2006 and 2007. Active and passive case detections identified Plasmodium infection by field microscopy and nested Polymerase Chain Reaction (PCR). HBV infections were identified by serology and confirmed by real-time PCR. Epidemiological information and plasma cytokine profiles were studied. The data were analyzed using adjusted multinomial logistic regression. Plasmodium-infected individuals with active HBV infection were more likely to be asymptomatic (OR: 120.13, P < 0.0001), present with lower levels of parasitemia and demonstrate a decreased inflammatory cytokine profile. Nevertheless, co-infected individuals presented higher HBV viremia. Plasmodium parasitemia inversely correlated with plasma HBV DNA levels (r=-0.6; P=0.0003). Conclusion: HBV infection diminishes the intensity of malaria infection in individuals from this endemic area. This effect seems related to cytokine balance and control of inflammatory responses. These findings add important insights to the understanding of the factors affecting the clinical outcomes of malaria in endemic regions.

Single-nucleotide polymorphism, linkage disequilibrium and geographic structure in the malaria parasite Plasmodium vivax: prospects for genome-wide association studies

Background: The ideal malaria parasite populations for initial mapping of genomic regions contributing to phenotypes such as drug resistance and virulence, through genome-wide association studies, are those with high genetic diversity, allowing for numerous informative markers, and rare meiotic recombination, allowing for strong linkage disequilibrium (LD) between markers and phenotype-determining loci. However, levels of genetic diversity and LD in field populations of the major human malaria parasite P. vivax remain little characterized. Results: We examined single-nucleotide polymorphisms (SNPs) and LD patterns across a 100-kb chromosome segment of P. vivax in 238 field isolates from areas of low to moderate malaria endemicity in South America and Asia, where LD tends to be more extensive than in holoendemic populations, and in two monkey-adapted strains (Salvador-I, from El Salvador, and Belem, from Brazil). We found varying levels of SNP diversity and LD across populations, with the highest diversity and strongest LD in the area of lowest malaria transmission. We found several clusters of contiguous markers with rare meiotic recombination and characterized a relatively conserved haplotype structure among populations, suggesting the existence of recombination hotspots in the genome region analyzed. Both silent and nonsynonymous SNPs revealed substantial between-population differentiation, which accounted for similar to 40% of the overall genetic diversity observed. Although parasites clustered according to their continental origin, we found evidence for substructure within the Brazilian population of P. vivax. We also explored between-population differentiation patterns revealed by loci putatively affected by natural selection and found marked geographic variation in frequencies of nucleotide substitutions at the pvmdr-1 locus, putatively associated with drug resistance. Conclusion: These findings support the feasibility of genome-wide association studies in carefully selected populations of P. vivax, using relatively low densities of markers, but underscore the risk of false positives caused by population structure at both local and regional levels.

Characterization of subgraph relationships and distribution in complex networks

A network can be analyzed at different topological scales, ranging from single nodes to motifs, communities, up to the complete structure. We propose a novel approach which extends from single nodes to the whole network level by considering non-overlapping subgraphs (i.e. connected components) and their interrelationships and distribution through the network. Though such subgraphs can be completely general, our methodology focuses on the cases in which the nodes of these subgraphs share some special feature, such as being critical for the proper operation of the network. The methodology of subgraph characterization involves two main aspects: (i) the generation of histograms of subgraph sizes and distances between subgraphs and (ii) a merging algorithm, developed to assess the relevance of nodes outside subgraphs by progressively merging subgraphs until the whole network is covered. The latter procedure complements the histograms by taking into account the nodes lying between subgraphs, as well as the relevance of these nodes to the overall subgraph interconnectivity. Experiments were carried out using four types of network models and five instances of real-world networks, in order to illustrate how subgraph characterization can help complementing complex network-based studies.

Relationship Between Surface Topography and Energy Density Distribution of Er,Cr:YSGG Beam on Irradiated Dentin: An Atomic Force Microscopy Study

Objective: The aim of this study was to assess by atomic force microscopy (AFM) the effect of Er,Cr:YSGG laser application on the surface microtopography of radicular dentin. Background: Lasers have been used for various purposes in dentistry, where they are clinically effective when used in an appropriate manner. The Er, Cr: YSGG laser can be used for caries prevention when settings are below the ablation threshold. Materials and Methods: Four specimens of bovine dentin were irradiated using an Er, Cr:YSGG laser (lambda = 2.78 mu m), at a repetition rate of 20 Hz, with a 750-mu m-diameter sapphire tip and energy density of 2.8 J/cm(2) (12.5 mJ/pulse). After irradiation, surface topography was analyzed by AFM using a Si probe in tapping mode. Quantitative and qualitative information concerning the arithmetic average roughness (Ra) and power spectral density analyses were obtained from central, intermediate, and peripheral areas of laser pulses and compared with data from nonirradiated samples. Results: Dentin Ra for different areas were as follows: central, 261.26 (+/- 21.65) nm; intermediate, 83.48 (+/- 6.34) nm; peripheral, 45.8 (+/- 13.47) nm; and nonirradiated, 35.18 (+/- 2.9) nm. The central region of laser pulses presented higher ablation of intertubular dentin, with about 340-760 nm height, while intermediate, peripheral, and nonirradiated regions presented no difference in height of peritubular and interperitubular dentin. Conclusion: According to these results, we can assume that even when used at a low-energy density parameter, Er, Cr: YSGG laser can significantly alter the microtopography of radicular dentin, which is an important characteristic to be considered when laser is used for clinical applications.

Impact of Manaus City on the Amazon Green Ocean atmosphere: ozone production, precursor sensitivity and aerosol load

As a contribution to the Large-Scale Biosphere-Atmosphere Experiment in Amazonia - Cooperative LBA Airborne Regional Experiment (LBA-CLAIRE-2001) field campaign in the heart of the Amazon Basin, we analyzed the temporal and spatial dynamics of the urban plume of Manaus City during the wet-to-dry season transition period in July 2001. During the flights, we performed vertical stacks of crosswind transects in the urban outflow downwind of Manaus City, measuring a comprehensive set of trace constituents including O(3), NO, NO(2), CO, VOC, CO(2), and H(2)O. Aerosol loads were characterized by concentrations of total aerosol number (CN) and cloud condensation nuclei (CCN), and by light scattering properties. Measurements over pristine rainforest areas during the campaign showed low levels of pollution from biomass burning or industrial emissions, representative of wet season background conditions. The urban plume of Manaus City was found to be joined by plumes from power plants south of the city, all showing evidence of very strong photochemical ozone formation. One episode is discussed in detail, where a threefold increase in ozone mixing ratios within the atmospheric boundary layer occurred within a 100 km travel distance downwind of Manaus. Observation-based estimates of the ozone production rates in the plume reached 15 ppb h(-1). Within the plume core, aerosol concentrations were strongly enhanced, with Delta CN/Delta CO ratios about one order of magnitude higher than observed in Amazon biomass burning plumes. Delta CN/Delta CO ratios tended to decrease with increasing transport time, indicative of a significant reduction in particle number by coagulation, and without substantial new particle nucleation occurring within the time/space observed. While in the background atmosphere a large fraction of the total particle number served as CCN (about 60-80% at 0.6% supersaturation), the CCN/CN ratios within the plume indicated that only a small fraction (16 +/- 12 %) of the plume particles were CCN. The fresh plume aerosols showed relatively weak light scattering efficiency. The CO-normalized CCN concentrations and light scattering coefficients increased with plume age in most cases, suggesting particle growth by condensation of soluble organic or inorganic species. We used a Single Column Chemistry and Transport Model (SCM) to infer the urban pollution emission fluxes of Manaus City, implying observed mixing ratios of CO, NO(x) and VOC. The model can reproduce the temporal/spatial distribution of ozone enhancements in the Manaus plume, both with and without accounting for the distinct (high NO(x)) contribution by the power plants; this way examining the sensitivity of ozone production to changes in the emission rates of NO(x). The VOC reactivity in the Manaus region was dominated by a high burden of biogenic isoprene from the background rainforest atmosphere, and therefore NO(x) control is assumed to be the most effective ozone abatement strategy. Both observations and models show that the agglomeration of NO(x) emission sources, like power plants, in a well-arranged area can decrease the ozone production efficiency in the near field of the urban populated cores. But on the other hand remote areas downwind of the city then bear the brunt, being exposed to increased ozone production and N-deposition. The simulated maximum stomatal ozone uptake fluxes were 4 nmol m(-2) s(-1) close to Manaus, and decreased only to about 2 nmol m(-2) s(-1) within a travel distance >1500 km downwind from Manaus, clearly exceeding the critical threshold level for broadleaf trees. Likewise, the simulated N deposition close to Manaus was similar to 70 kg N ha(-1) a(-1) decreasing only to about 30 kg N ha(-1) a(-1) after three days of simulation.

Kinetic effect on low frequency Alfven continuum in tokamaks

Using a quasi-toroidal set of coordinates in plasmas with coaxial circular magnetic surfaces, the Vlasov equation is solved, and dielectric tensor is found for large aspect ratio tokamaks in a low frequency band. Taking into account the q-profile and drift effects, Alfven wave continuum deformation by geodesic effects is analyzed. It is shown that the Alfven continuum has a minimum defined by the ion thermal velocity at the rational magnetic surfaces q(s)=-M/N, where M and N are the poloidal and toroidal mode numbers, respectively, and the parallel wave number is zero. Low frequency global Alfven waves are found below the continuum minimum. In hot ion plasmas, the geodesic term changes sign, provoking some deformation of Alfven velocity by a factor (1+q(2))(-1/2), and the continuum minimum disappears. (C) 2008 American Institute of Physics.