Susceptibility of Mycobacterium tuberculosis to first-line antimycobacterial agents in a Brazilian hospital: assessing the utility of the tetrazolium (MTT) microplate assay

We conducted a cross-sectional, hospital-based study between January 2006-March 2008 to estimate the resistance of Mycobacterium tuberculosis to first-line drugs in patients with tuberculosis at a Brazilian hospital. We evaluated the performance of the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) microplate assay compared with the Bactec-MGIT 960�� system for mycobacteria testing. The prevalence of resistance in M. tuberculosis was 6.7%. Multidrug-resistance [resistance to rifampicin (RMP) and isoniazid (INH)], INH-resistance and streptomycin (SM)-resistance accounted for 1%, 3.8% and 3.8% of all resistance, respectively, and all isolates were susceptible to ethambutol (EM). The resistance was primary in four cases and acquired in three cases and previous treatment was associated with resistance (p = 0.0129). Among the 119 M. tuberculosis isolates, complete concordance of the results for INH and EM was observed between the MTT microplate and Bactec-MGIT 960TM methods. The observed agreement for RMP was 99% (sensitivity: 90%) and 95.8% for SM (sensitivity 90.9%), lower than those for other drugs. The MTT colourimetric method is an accurate, simple and low-cost alternative in settings with limited resources.

Pharmacokinetic and pharmacodynamic effects of YM087, a combined V1/V2 vasopressin receptor antagonist in normal subjects.

OBJECTIVE: The pharmacokinetic and pharmacodynamic properties of YM087, (4'-[(2-methyl-1,4,5,6- tetrahydroimidazo[4,5-d][1]benzazepin-6-yl)-carbonyl]-2-p henylbenzanilide monohydrochloride), a new orally active, dual V1/V2 receptor antagonist were characterised in healthy normotensive subjects. METHODS: Six subjects were randomly allocated to receive, at 1-week intervals, a single oral dose of 60 mg YM087 and a single i.v. dose of 50 mg YM087 in an open-label, crossover study. RESULTS: YM087 had an oral bioavailability of 44% and a short half-life. Upon oral and i.v. administration of YM087, a significant sevenfold increase in urine flow rate and a fall in urinary osmolality (from 600 mosmol/l to less than 100-mosmol/l) were observed with a peak effect 2 h after drug intake suggesting effective vasopressin V2 receptor blockade. Simultaneously, significant increases in plasma osmolality (from 283 +/- 1.3 mosmol/l to 288 +/- 1.0 mosmol/l after i.v. and from 283 +/- 2.1 mosmol/l to 289 +/- 1.7-mosmol/l after oral administration) and vasopressin levels (from 1.5 +/- 0.3 pg/ml to 3.7 +/- 0.6 pg/ml after i.v. and from 0.9 +/- 0.1 pg/ml to 3.9 +/- 0.7 pg/ml after oral administration) were found. When administered i.v., YM087 inhibited the vasopressin-induced skin vasoconstriction, suggesting a blockade of V1 receptors. However, the YM087-induced antagonism of V1 receptors was less pronounced than V2 receptor blockade. CONCLUSION: These data show that YM087 is an effective dual V1/V2 receptor antagonist in man.

Activation of GPER-1 estradiol receptor downregulates production of testosterone in isolated rat Leydig cells and adult human testis.

PURPOSE: Estradiol (E2) modulates testicular functions including steroidogenesis, but the mechanisms of E2 signaling in human testis are poorly understood. GPER-1 (GPR30), a G protein-coupled membrane receptor, mediates rapid genomic and non-genomic response to estrogens. The aim of this study was to evaluate GPER-1 expression in the testis, and its role in estradiol dependent regulation of steroidogenesis in isolated rat Leydig cells and human testis. MATERIALS AND METHODS: Isolated Leydig cells (LC) from adult rats and human testicular tissue were used in this study. Expression and localization studies of GPER-1 were performed with qRT-PCR, immunofluorescence, immunohistochemistry and Western Blot. Luteinizing Hormone (LH) -stimulated, isolated LC were incubated with estradiol, G-1 (GPER-1-selective agonist), and estrogen receptor antagonist ICI 182,780. Testosterone production was measured with radioimmunoassay. LC viability after incubation with G-1 was measured using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. RESULTS: GPER-1 mRNA is abundantly expressed in rat LC and human testis. Co-localization experiments showed high expression levels of GPER-1 protein in LC. E2-dependent activation of GPER-1 lowers testosterone production in isolated rats LCs and in human testis, with statistically and clinically significant drops in testosterone production by 20-30% as compared to estradiol-na��ve LC. The exposure to G-1 does not affect viability of isolated LCs. CONCLUSIONS: Our results indicate that activation of GPER-1 lowers testosterone levels in the rat and human testis. The expression of GPER-1 in human testis, which lack ERα, makes it an exciting target for developing new agents affecting testosterone production in men.

Anti-Mycobacterium tuberculosis activity and cytotoxicity of Calophyllum brasiliense Cambess (Clusiaceae)

We evaluated the in vitro anti-Mycobacterium tuberculosis activity and the cytotoxicity of dichloromethane extract and pure compounds from the leaves of Calophyllum brasiliense. Purification of the dichloromethane extract yielded the pure compounds (-) mammea A/BB (1), (-) mammea B/BB (2) and amentoflavone (3). The compound structures were elucidated on the basis of spectroscopic and spectrometric data. The contents of bioactive compounds in the extracts were quantified using high performance liquid chromatography coupled to an ultraviolet detector. The anti-M. tuberculosis activity of the extracts and the pure compounds was evaluated using a resazurin microtitre assay plate. The cytotoxicity assay was performed in J774G.8 macrophages using the 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide colourimetric method. The quantification of the dichloromethane extract showed (1) and (2) at concentrations of 31.86 ± 2.6 and 8.24 ± 1.1 µg/mg of extract, respectively. The dichloromethane and aqueous extracts showed anti-M. tuberculosis H37Rv activity of 62.5 and 125 µg/mL, respectively. Coumarins (1) and (2) showed minimal inhibitory concentration ranges of 31.2 and 62.5 µg/mL against M. tuberculosis H37Rv and clinical isolates. Compound (3) showed no activity against M. tuberculosis H37Rv. The selectivity index ranged from 0.59-1.06. We report the activity of the extracts and coumarins from the leaves of C. brasiliense against M. tuberculosis.

BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation.

Effects of triamcinolone acetonide on vessels of the posterior segment of the eye.

PURPOSE: This study investigates the effects of triamcinolone acetonide (TA) on retinal endothelial cells in vitro and explores the potential vascular toxic effect of TA injected into the vitreous cavity of rats in vivo. METHODS: Subconfluent endothelial cells were treated with either 0.1 mg/ml or 1 mg/ml TA in 1% ethanol. Control cells were either untreated or exposed to 1% ethanol. Cell viability was evaluated at 24 h, 72 h, and five days using the tetrazolium 3-(4,5-dimethylthiazol-2-yl)-2,5 phenyltetrazolium bromide test (MTT) and lactate dehydrogenase (LDH) assays. Cell proliferation was evaluated by 5-bromo-2-deoxyuridine (BrdU) test. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL assay), annexin-binding, and caspase 3 activation. Caspase-independent cell deaths were investigated by immunohistochemistry using antibodies against apoptosis inducing factor (AIF), cytochrome C, microtubule-associated protein (MAP)-light chain 3 (MAP-LC3), and Leukocyte Elastase Inhibitor/Leukocyte Elastase Inhibitor-derived DNase II (LEI/L-DNase II). In vivo, semithin and ultrathin structure analysis and vascular casts were performed to examine TA-induced changes of the choroidal vasculature. In addition, outer segments phagocytosis assay on primary retinal pigment epithelium (RPE) cells was performed to assess cyclooxygenase (COX-2) and vascular endothelial growth factor (VEGF) mRNAs upregulation with or without TA. RESULTS: The inhibitory effect of TA on cell proliferation could not explain the significant reduction in cell viability. Indeed, TA induced a time-dependent reduction of bovine retinal endothelial cells viability. Annexin-binding positive cells were observed. Cytochrome C was not released from mitochondria. L-DNase II was found translocated to the nucleus, meaning that LEI was changed into L-DNase II. AIF was found nuclearized in some cells. LC3 labeling showed the absence of autophagic vesicles. No autophagy or caspase dependent apoptosis was identified. At 1 mg/ml TA induced necrosis while exposure to lower concentrations for 3 to 5 days induced caspase independent apoptosis involving AIF and LEI/L-DNase II. In vivo, semithin and ultrathin structure analysis and vascular casts revealed that TA mostly affected the choroidal vasculature with a reduction of choroidal thickness and increased the avascular areas of the choriocapillaries. Experiments performed on primary RPE cells showed that TA downregulates the basal expression of COX-2 and VEGF and inhibits the outer segments (OS)-dependent COX-2 induction but not the OS-dependent VEGF induction. CONCLUSIONS: This study demonstrates for the first time that glucocorticoids exert direct toxic effect on endothelial cells through caspase-independent cell death mechanisms. The choroidal changes observed after TA intravitreous injection may have important implications regarding the safety profile of TA use in human eyes.

Anti-cancer activity of 5-O-alkyl 1,4-imino-1,4-dideoxyribitols.

New derivatives of 1,4-dideoxy-1,4-imino-D-ribitol have been prepared and evaluated for their cytotoxicity on solid and haematological malignancies. 1,4-Dideoxy-5-O-[(9Z)-octadec-9-en-1-yl]-1,4-imino-D-ribitol (13, IC(50) &#8764;2 &#956;M) and its C(18)-analogues (IC(50) <10 &#956;M) are cytotoxic toward SKBR3 (breast cancer) cells. 13 also inhibits (IC(50) &#8764;8 &#956;M) growth of JURKAT cells.

Prox1 interacts with Atoh1 and Gfi1, and regulates cellular differentiation in the inner ear sensory epithelia.

Inner ear hair cells and supporting cells arise from common precursors and, in mammals, do not show phenotypic conversion. Here, we studied the role of the homeodomain transcription factor Prox1 in the inner ear sensory epithelia. Adenoviral-mediated Prox1 transduction into hair cells in explant cultures led to strong repression of Atoh1 and Gfi1, two transcription factors critical for hair cell differentiation and survival. Luciferase assays showed that Prox1 can repress transcriptional activity of Gfi1 independently of Atoh1. Prox1 transduction into cochlear outer hair cells resulted in degeneration of these cells, consistent with the known phenotype of Gfi1-deficient mice. These results together with the widespread expression of endogenous Prox1 within the population of inner ear supporting cells point to the role for Prox1 in antagonizing the hair cell phenotype in these non-sensory cells. Further, in vivo analyses of hair cells from Gfi1-deficient mice suggest that the cyclin-dependent kinase inhibitor p57(Kip2) mediates the differentiation- and survival-promoting functions of Gfi1. These data reveal novel gene interactions and show that these interactions regulate cellular differentiation within the inner ear sensory epithelia. The data point to the tight regulation of phenotypic characteristics of hair cells and supporting cells.

International variation in management of screen-detected ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) incidence has grown with the implementation of screening and its detection varies across International Cancer Screening Network (ICSN) countries. The aim of this survey is to describe the management of screen-detected DCIS in ICSN countries and to evaluate the potential for treatment related morbidity. METHODS: We sought screen-detected DCIS data from the ICSN countries identified during 2004-2008. We adopted standardised data collection forms and analysis and explored DCIS diagnosis and treatment processes ranging from pre-operative diagnosis to type of surgery and radiotherapy. RESULTS: Twelve countries contributed data from a total of 15 screening programmes, all from Europe except the United States of America and Japan. Among women aged 50-69years, 7,176,050 screening tests and 5324 screen-detected DCIS were reported. From 21% to 93% of DCIS had a pre-operative diagnosis (PO); 67-90% of DCIS received breast conservation surgery (BCS), and in 41-100% of the cases this was followed by radiotherapy; 6.4-59% received sentinel lymph node biopsy (SLNB) only and 0.8-49% axillary dissection (ALND) with 0.6% (range by programmes 0-8.1%) being node positive. Among BCS patients 35% received SLNB only and 4.8% received ALND. Starting in 2006, PO and SLNB use increased while ALND remained stable. SLNB and ALND were associated with larger size and higher grade DCIS lesions. CONCLUSIONS: Variation in DCIS management among screened women is wide and includes lymph node surgery beyond what is currently recommended. This indicates the presence of varying levels of overtreatment and the potential for its reduction.

Tapiola-ryhm��n Yhti��kokousj��rjestelm��-ohjelmiston m����rittely ja suunnittelu

T��ss�� insin����rity��ss�� selvitettiin mahdollisuuksia parantaa Tapiola-ryhm��n Yhti��kokousj��rjestelm��-ohjelmiston ominaisuuksia ja tietoturvallisuutta. J��rjestelm���� k��ytet����n Tapiola-ryhm��n vakuutusyhti��iden yhti��kokouksiin osallistuvien osakkaiden kirjaamiseen ja heid��n ����nten laskentaan. Tutkimuksen perusteella tehtiin j��rjestelm��n m����rittely ja suunnittelu, joiden tuloksena syntyiv��t toiminnallinen ja tekninen m����rittelydokumentaatio, jotka toimivat pohjana uuden Yhti��kokousj��rjestelm��n toteutukselle. Ty�� tehtiin Tapiola-ryhm��lle Tieto-Tapiola Oy:n tilauksesta. Ty��n alussa tutkittiin erilaisia mahdollisuuksia toteuttaa j��rjestelm��n ohjelmisto- ja tietokanta-arkkitehtuuri, joiden perusteella m����rittely�� ja suunnittelua alettiin toteuttaa. Tutkimuksen perusteella p����dyttiin k��ytt��m����n Java SE -arkkitehtuuria sovelluksen toteutukseen ja SQL Server -tietokantaa j��rjestelm��n tietovarastona. Valittuihin ratkaisuihin p����dyttiin niiden hyvien tietoturvallisuus- ja kertakirjausominaisuuksien takia. Toiminnallisessa m����rittelydokumentissa k��yd����n l��pi j��rjestelm��lle asetettuja vaatimuksia ja kuvataan sen toiminnot, liiketoimintaluokkamalli, k��ytt��liittym�� ja tulosteet. Lis��ksi siin�� otetaan kantaa j��rjestelm��n k��ytt��ymp��rist����n, ulkoisiin tietokantaliittymiin, k��ytt��j��n tunnistautumiseen ja tietoturvallisuuteen sek�� k��yd����n l��pi sen toiminta k��ytt��jien n��k��kulmasta. Toiminnallisen m����rittelydokumentin pohjalta luotiin tekninen m����rittelydokumentti. Siin�� kuvataan j��rjestelm��n ymp��rist�� ja ohjelmisto- sek�� tietokanta-arkkitehtuuri yleisell�� tasolla. T��m��n lis��ksi j��rjestelm��n arkkitehtuuria k��yd����n my��s tarkemmin l��pi sek�� kuvataan moduulit ja toiminnot niin tarkasti, ett�� niiden perusteella voidaan toteuttaa koko j��rjestelm��. Ty��n tuloksena syntyiv��t kattava toiminnallinen ja tekninen m����rittelydokumentaatio, joissa k��yd����n l��pi kaikki j��rjestelm��n toteuttamiseen tarvittavat elementit sill�� tarkkuudella, ett�� j��rjestelm��n toteuttaminen voidaan aloittaa.

Airbus 340 -lentokoneen C-huoltotelakoiden layout-suunnitelma

T��ss�� insin����rity��ss�� tehtiin layout-suunnitelmat C-huoltotelakoista Airbus 340 -lentokoneiden huoltoa varten ja selvitettiin samojen huoltotelakoiden k��ytt��mahdollisuutta my��s muiden konetyyppien huolloissa. Insin����rity��n toimeksiantajana toimi Finnairin tekniikan lentokonekorjaamo, jonka k��ytt����n huoltotelakat suunniteltiin. Ty�� aloitettiin perehtym��ll�� Airbus 340 -lentokoneen mittoihin ja C-huoltotarpeisiin. Seuraavaksi k��ytiin l��pi erilaisia huoltotelakkavaihtoehtoja ja niiden aiheuttamia kustannuksia pitk��ll�� ajanjaksolla. Huoltotelakoiden soveltuvuutta tarkasteltiin eri lentokonetyypien k��ytt����n. Huoltotelakoiden suunnittelussa huomioitiin my��s niiden varastointivaatimukset. Lis��ksi ty��ss�� k��ytiin l��pi viranomaisten turvallisuusvaatimukset sek�� lentokonehuoltotoiminnan erityisvaatimukset huoltotelakoille. Ty��n tuloksena syntyneit�� investointilaskelmia ja layout-suunnitelmia k��ytet����n hy��dyksi valittaessa kustannuksiltaan ja k��ytt��vaatimuksiltaan parhaiten Airbus 340 -lentokoneiden C-huoltovaatimuksia vastaava huoltotelakkavaihtoehto. Huoltotelakoiden layout-suunnitelmat on tehty ty��ntekij��iden n��k��kulmat huomioiden, jotta ty��nteko olisi tehokasta ja ergonomista.

Konstikas kirjoittaminen ja kirjoittamisen konstit

Opinn��ytteemme aiheena on kirjoittamisen kehittyminen, vaikeudet ja tukikeinot 1. ja 2. luokan oppilailla. Ty��el��m��n yhteisty��kumppanit opinn��ytety��ss��mme olivat Tikkurilan terveysaseman toimintaterapeutit. Opinn��ytety��mme tarkoitus oli tehd�� yhteisty��kumppaneiden k��ytt����n kirjallista materiaalia konsultaation tueksi kirjoittamisen vaikeuksista k��rsivien lasten kouluty��skentelyyn. Ty�� on rajattu k��sittelem����n kirjoittamista k��den taitona. Rajauksesta johtuen k��sittelemme ty��ss��mme kirjoittamista p����osin k��sialan tuottamisen n��k��kulmasta, mutta emme perehdy kirjoitetun tekstin sis��ll��n tuottamiseen. Toimintaterapeuttien tarkoituksena on luovuttaa ty��st�� heid��n mielest����n tarpeellinen tieto eteenp��in opettajille oppilaan kirjoittamisen arvioinnin j��lkeen. Opinn��ytety��mme muoto on teoreettinen, kirjallisuuskatsauksen tyyppinen ty��. Ty��mme l��htein�� k��ytimme p����osin toimintaterapia-alan lasten kirjoittamista k��sittelev���� kirjallisuutta ja tieteellisi�� tutkimusartikkeleita. L��ysimme opinn��ytety��t��mme tehdess��mme runsaasti kirjoittamisen tukemisen keinoja toimintaterapian n��k��kulmasta. Kirjoittamisen tukemista koululuokassa k��sittelimme lapsen koulunk��ynnist�� selviytymisen n��k��kulmasta coping-viitekehyst�� hy��dynt��en. Ennen kirjoittamisen tukemiseen liittyvien keinojen selvitt��mist�� ty��ss�� oli tarpeellista selvitt���� kirjoittamisen kannalta olennaisia asioita. N��it�� olivat kirjoittamisen kehittyminen k��den taitona, kirjoittamiseen vaadittavat taidot ja valmiudet, kouluymp��rist��n vaatimukset kirjoittamiselle, sek�� kirjoittamisessa ilmenev��t vaikeudet ja niiden vaikutukset oppilaan toimintaan. Kirjoittaminen on vaativa ja monimutkainen taito. Se on arvokas, koulunk��ynti�� ja oppimista mahdollistava v��linetaito. Vaikeudet kirjoittamisessa voivat johtua useista eri syist��, joten yht�� oikeaa keinoa tai menetelm���� kirjoittamisen tukemiseen ei ole. Kirjoittamista koululuokassa voidaan pyrki�� tukemaan toimintataterapian n��k��kulmasta vaikuttamalla oppilaan sis��isiin voimavaroihin, ja/tai kouluymp��rist��n voimavaroihin. Oppilaan suoriutumista kirjoittamisesta voidaan tukea my��s toiminnan vaatimuksia muuttamalla. Toivoisimme, ett�� tulevilta opinn��ytteen tekij��ilt�� l��ytyisi kiinnostusta jatkaa ty��t��mme. Ehdotuksiamme jatkoty��n aiheiksi ovat Opas kirjoittamisen tukemiseksi opettajille, tai Opas kirjoittamisen tukemiseksi toimintaterapeuteille.

Liian hapokasta : terveyden edist��misprojekti 14-18 vuotiaille mielenterveyskuntoutujanuorille

T��m��n toiminnallisen opinn��ytety��n tarkoitus oli toteuttaa suun terveyden edist��misn��ytelm��. HUS:n Kipin�� ja Kunttari kuntoutumisosastoille, joiden asukkaat ovat 14-18-vuotiaita mielenterveyskuntoutujia. Opinn��ytety��n tavoitteena oli lis��t�� nuorten suun terveydenlukutaitoa. N��ytelm��n tavoitteena oli innostaa nuoria suun terveydenhoitoon. Terveydenedist��mismenetelm��n�� k��ytettiin draamaa. Lukuisat tutkimukset viittaavat siihen, ett�� nuorten elintavat ovat muuttuneet ep��terveellisemp����n suuntaan. Alueelliset terveyserot heijastuvat my��s suunterveyteen. Helsingiss�� on moniongelmaisia perheit��, nuoria ja lapsia suhteellisesti enemm��n kuin muualla Suomessa. Opinn��ytety��ss�� sovellettiin Precede-Proceed -terveyden edist��mismallia, joka n��kyy ty��mme suunnittelu-, toteutus- ja arviointivaiheessa. Suun terveydenedist��misn��ytelm�� ���Liian hapokasta��� suunniteltiin ja toteutettiin opinn��ytety��ryhm��ss�� yhteisty��ss�� ty��el��m��yhteisty��kumppanin kanssa. N��ytelm�� oli luonteeltaan osallistava. T��m�� tarkoittaa sit��, ett�� yleis�� sai itse vaikuttaa n��ytelm��n kulkuun valitsemalla kahdesta eri vaihtoehdosta sopivimman. N��ytelm��n keskeiset aihealueet valittiin n��ytt����n ja kokemukseen perustuen ja ne olivat: suun hoito, tupakointi, iensairaudet, karies ja ravitsemus. T��lle ty��lle sovellus- ja jatkomahdollisuudet voisivat olla tutkia millaisen terveyden lukutaidon nuoret saavuttivat. Ty��mme voi toimia my��s esimerkkin�� tulevien terveyden edist��misn��ytelmien toteutuksille ja k��sikirjoituksille.

Covariant Phase Observables in Quantum Mechanics

The aim of this thesis is to present a solution to the quantum phase problem of the single-mode optical field. The solution is based on the use of phase shift covariant normalized positive operator measures. These measures describe realistic direct coherent state phase measurements such as the phase measurement schemes based on eight-port homodyne detection or heterodyne detection. The structure of covariant operator measures and, more generally, covariant sesquilinear form measures is analyzed in this work. Four different characterizations for phase shift covariant normalized positive operator measures are presented. The canonical covariant operator measure is definded and its properties are studied. Finally, some other suggested phase theories are introduced to investigate their connections to the covariant sesquilinear form measures.