Pregnancy outcome in women with polycystic ovary syndrome in relation to second-trimester testosterone levels.

RESEARCH QUESTION: Do women with polycystic ovary syndrome (PCOS) have higher testosterone levels during pregnancy and what role does high testosterone play in the development of obstetric complications? DESIGN: Retrospective cohort study from Uppsala University Hospital, Sweden. The study population consisted of women with PCOS (n = 159) and a comparison group of women without PCOS matched for body mass index (n = 320). Plasma testosterone levels were measured in the early second trimester by liquid chromatography with tandem mass spectrometry, and women with PCOS were grouped into tertiles according to their testosterone levels. Possible associations with obstetric complications, maternal metabolic factors and offspring birth weight were explored by multivariable logistic and linear regression models. RESULTS: Compared with women who do not have PCOS, women with PCOS had higher total testosterone (median 1.94, interquartile range [IQR] 1.21-2.64 versus 1.41, IQR 0.89-1.97; P < 0.001), and free androgen index (median 0.25, IQR 0.15-0.36 versus 0.18, IQR 0.11-0.28; P < 0.001). Women with PCOS who had the highest levels of testosterone had increased risk for preeclampsia, even when adjusted for age, parity, country of birth and smoking (adjusted OR 6.16, 95% CI 1.82 to 20.91). No association was found between high testosterone in women with PCOS and other obstetric complications. CONCLUSIONS: Women with PCOS have higher levels of total testosterone and free androgen index during pregnancy than women without PCOS matched for body mass index. Preliminary evidence shows that women with PCOS and the highest maternal testosterone levels in early second trimester had the highest risk of developing preeclampsia. This finding, however, is driven by a limited number of cases and should be interpreted with caution.

Biodegradation of endocrine disrupting chemicals benzyl butyl phthalate and dimethyl phthalate by Bacillus marisflavi RR014.

AIM: The objectives of the present study were to explore the benzyl butyl phthalate (BBP) and dimethyl phthalate (DMP) degradation potential of Bacillus marisflavi RR014 isolated from the tap water of public toilet and also to optimize the phthalates degradation process using response surface methodology. METHODS AND RESULTS: The minimal salt medium was used for the biodegradation analysis of phthalates. The quantification of phthalates and their intermediate metabolites identification were done by using UHPLC and LC-MS/MS respectively. The results revealed that B. marisflavi RR014 is capable of degrading both the phthalates under varying pH, temperature and salinity conditions. The formation of phthalic acid from the breakdown of BBP and DMP (500 mg l-1 ) in the medium was observed after 24 h. After 72 h, 61% of BBP and 98·9% of DMP in the medium was degraded as monitored by UHPLC. The identification of intermediate metabolites by LC-MS/MS revealed that hydrolysis of BBP and DMP produces phthalic acid. CONCLUSIONS: The degradation rate of both the phthalates was increased as the parameters increased up to an optimum level. The three environmental factors (pH, temperature and salt concentration) strongly affect the rate of degradation of both the phthalates. The maximum degradation rate for both the phthalates was achieved at pH 7, temperature 35°C and salt concentration of 1% as observed from the central composite experimental design. SIGNIFICANCE AND IMPACT OF THE STUDY: It is the first report on the phthalates biodegradation potential of B. marisflavi RR014 isolated from the tap water of public toilet. The bacterium is capable of degrading BBP and DMP under varying pH, temperature and salinity, therefore, ideal to treat the phthalate contaminated environments.

Concentrations of canine prostate specific esterase, CPSE, at baseline are associated with the relative size of the prostate at three-year follow-up.

BACKGROUND: Enlargement of the prostate is associated with prostatic diseases in dogs, and an estimation of prostatic size is a central part in the diagnostic workup. Ultrasonography is often the method of choice, but biomarkers constitute an alternative. Canine prostate specific esterase (CPSE) shares many characteristics with human prostate specific antigen (PSA) and is related to prostate size. In men with clinical symptoms of prostatic disease, PSA concentrations are related to prostate growth. The aims of the present follow-up study were to evaluate if the concentration of CPSE is associated with future growth of the prostate, and if analysis of a panel of 16 steroids gives further information on prostatic growth. Owners of dogs included in a previous study were 3 years later contacted for a follow-up study that included an interview and a clinical examination. The prostate was examined by ultrasonography. Serum concentrations of CPSE were measured, as was a panel of steroids. RESULTS: Of the 79 dogs included at baseline, owners of 77 dogs (97%) were reached for an interview, and 22 were available for a follow-up examination. Six of the 79 dogs had clinical signs of prostatic disease at baseline, and eight of the remaining 73 dogs (11%) developed clinical signs between baseline and follow-up, information was lacking for two dogs. Development of clinical signs was significantly more common in dogs with a relative prostate size of ≥2.5 at baseline (n = 20) than in dogs with smaller prostates (n = 51). Serum concentrations of CPSE at baseline were not associated with the change in prostatic size between baseline and follow-up. Serum concentrations of CPSE at baseline and at follow-up were positively associated with the relative prostatic size (Srel) at follow-up. Concentrations of corticosterone (P = 0.024), and the class corticosteroids (P = 0.0035) were positively associated with the difference in Srel between baseline and follow-up. CONCLUSIONS: The results support the use of CPSE for estimating present and future prostatic size in dogs ≥4 years, and the clinical usefulness of prostatic size for predicting development of clinical signs of prostatic disease in the dog. The association between corticosteroids and prostate growth warrants further investigation.

Hormonal determinants of mammographic density and density change.

BACKGROUND: Mammographic density (MD) is a strong risk factor for breast cancer. We examined how endogenous plasma hormones are associated with average MD area (cm2) and annual MD change (cm2/year). METHODS: This study within the prospective KARMA cohort included analyses of plasma hormones of 1040 women. Hormones from the progestogen (n = 3), androgen (n = 7), oestrogen (n = 2) and corticoid (n = 5) pathways were analysed by ultra-performance supercritical fluid chromatography-tandem mass spectrometry (UPSFC-MS/MS), as well as peptide hormones and proteins (n = 2). MD was measured as a dense area using the STRATUS method (mean over the left and right breasts) and mean annual MD change over time. RESULTS: Greater baseline mean MD was associated with overall higher concentrations of progesterone (average + 1.29 cm2 per doubling of hormone concentration), 17OH-progesterone (+ 1.09 cm2), oesterone sulphate (+ 1.42 cm2), prolactin (+ 2.11 cm2) and SHBG (+ 4.18 cm2), and inversely associated with 11-deoxycortisol (- 1.33 cm2). The association between MD and progesterone was confined to the premenopausal women only. The overall annual MD change was - 0.8 cm2. Hormones from the androgen pathway were statistically significantly associated with MD change. The annual MD change was - 0.96 cm2 and - 1.16 cm2 lesser, for women in the highest quartile concentrations of testosterone and free testosterone, respectively, compared to those with the lowest concentrations. CONCLUSIONS: Our results suggest that, whereas hormones from the progestogen, oestrogen and corticoid pathways drive baseline MD, MD change over time is mainly driven by androgens. This study emphasises the complexity of risk factors for breast cancer and their mechanisms of action.

Workplace violence against doctors: Characteristics, risk factors, and mitigation strategies.

Workplace violence is a major occupational issue concerning doctors that has a significant impact on their physical and psychological well-being. This ultimately affects the health care services of the country. Patient-led episodes of verbal violence are more prevalent in Asian countries, especially in the emergency department, psychiatric wards, and intensive care units, mostly faced by junior doctors and residents. Some common precursors of violence against doctors are patients and their attendants' dissatisfaction and low impulse control, poor administration, miscommunication, infrastructural issues especially differences in services between private and public hospitals, and negative media portrayal of doctors. The assessment of risk factors, development and implementation of workplace violence programs, and addressing underreporting of violent episodes have been suggested as some successful organizational mitigation strategies. Recommendations on the management of workplace violence include the development of participative, gender-based, culture-based, nondiscriminatory, and systematic strategies to deal with issues related to violence. This article aims to present a comprehensive review of workplace violence against doctors, discussing the prevalence, degree of violence, predictors, impact on physical and psychological health and intervention strategies to devise practical actions against workplace violence.

A novel, fast and sensitive supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) method for analysis of arachidonic acid metabolites.

The development of a rapid, sensitive and reliable method for the quantification of bioactive arachidonic acid metabolites (AA-metabolites) in biological samples is quite challenging due to the minute concentration, short half-life and their structural complexity arising from different isomers. In this study, a simple, fast and environmentally friendly supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) method was developed and validated for simultaneous measurement of five (PGD2, PGE2, PGF2α, 6KetoPGF1α and LTB4) AA-metabolites in biological samples. These analytes were extracted by protein precipitation followed by separation and quantification. The analysis was completed within 3 minutes. The matrix matched linear calibration ranged from 0.5-100 ng mL-1 (r2 ≥ 0.995), whilst, the limit of quantification of PGD2, PGE2, PGF2α, and LTB4 was 0.5 ng mL-1 and was 2.5 ng mL-1 for 6KetoPGF1α. The interday and intraday precisions of the method were less than 15% while the accuracy of most of the analytes varied between 83 and 109%. Finally, as a proof of concept, the method was successfully applied for the determination of eicosanoids in human samples, which expands the possibility to explore physiological states, disease phenotypes, and novel biomarkers.

McCall Culdoplasty during Total Laparoscopic Hysterectomy: A Pilot Randomized Controlled Trial.

STUDY OBJECTIVE: To assess the feasibility and safety of a McCall culdoplasty at the time of total laparoscopic hysterectomy and to evaluate the differences in the total vaginal length, vaginal apex during Valsalva, and sexual function 12 months after McCall culdoplasty compared with standard cuff closure. DESIGN: A pilot randomized controlled, single-masked trial (Canadian Task Force classification I). SETTING: An academic tertiary care hospital. PATIENTS: Women undergoing total laparoscopic hysterectomy for benign indications from June 2013 to December 2013. INTERVENTIONS: Women were randomized (1:1) to McCall culdoplasty followed by standard cuff closure versus standard cuff closure. Patients underwent Pelvic Organ Prolapse Quantification examination and completed the Female Sexual Function Index immediately before surgery and at 6 months and 12 months postoperatively. The primary outcome was the operative time. Secondary outcomes included estimated blood loss, complications, total vaginal length, vaginal apex during Valsalva, and sexual function. MEASUREMENTS AND MAIN RESULTS: This study included 50 patients. The groups were similar in terms of preoperative and surgical characteristics. The operative time did not differ between the groups. The estimated blood loss and complications were also similar. The loss to follow-up was similar in both groups. Changes in the total vaginal length, vaginal apex during Valsalva, sexual function, and pain with intercourse did not differ between the groups. CONCLUSION: In this pilot study, the addition of McCall culdoplasty to standard cuff closure during total laparoscopic hysterectomy was not associated with an increase in operative time, estimated blood loss, or surgical complications. No differences in the total vaginal length or vaginal apex during Valsalva were observed at the 12-month follow-up. There were no differences in sexual dysfunction or dyspareunia. Given the well-established risk reduction for the development of apical prolapse with McCall culdoplasty during vaginal hysterectomy, this procedure may be a feasible and safe addition to total laparoscopic hysterectomy.

Gold-Catalyzed Concomitant [3 + 3] Cycloaddition/Cascade Heterocyclization of Enynones/Enynals with Azides Leading to Furanotriazines.

[Au]-catalyzed [3 + 3] cycloaddition reaction of enynones/enynals with azides, which allows the efficient regioselective synthesis of highly fused furo[3,4-d][1,2,3]triazines in good-to-excellent yields under mild conditions, has been developed. The synthetic utility of furanotriazines was exploited by oxidation with cerium ammonium nitrate (CAN) affording highly functionalized dihydrotriazines. Both furo[3,4-d][1,2,3]triazines and dihydrotriazines exhibit good fluorescence activity.

In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia.

BACKGROUND: Cytochrome P450 3A (CYP3A) isoenzyme metabolic activity varies between individuals and is therefore a possible candidate of influence on the therapeutic outcome of the tyrosine kinase inhibitor imatinib in patients with chronic myeloid leukemia (CML). The aim of this study was to investigate the influence of CYP3A metabolic activity on the plasma concentration and outcome of imatinib in patients with CML. METHODS: Forty-three patients with CML were phenotyped for CYP3A activity using quinine as a probe drug and evaluated for clinical response parameters. Plasma concentrations of imatinib and its main metabolite, CGP74588, were determined using liquid chromatography-mass spectrometry. RESULTS: Patients with optimal response to imatinib after 12 months of therapy did not differ in CYP3A activity compared to nonoptimal responders (quinine metabolic ratio of 14.69 and 14.70, respectively; P = 0.966). Neither the imatinib plasma concentration nor the CGP74588/imatinib ratio was significantly associated with CYP3A activity. CONCLUSIONS: The CYP3A activity does not influence imatinib plasma concentrations or the therapeutic outcome. These results indicate that although imatinib is metabolized by CYP3A enzymes, this activity is not the rate-limiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations.

Hypertriglyceridemia: a possible diagnostic marker of disease severity in visceral leishmaniasis.

PURPOSE: Visceral leishmaniasis (VL), a protozoan disease, is 100% fatal if left untreated. Anemia is common in VL which plays a role in expression of clinically overt VL disease. Laboratory clues are scarce for strengthening clinical suspicion for severity in VL. Hypertriglyceridemia has emerged as a new concept for the diagnosis and prognosis in VL. The present study is aimed at correlating the magnitude of hypertriglyceridemia with the severity in VL. MATERIALS AND METHODS: A retrospective case-control study was conducted between January 2012 to December 2013 among 124 patients coming for treatment from VL endemic areas, who had fever of more than 15 days and did not respond to antimalarials and antibiotics. The parasitologically confirmed VL cases (n = 87) were categorized as mild/moderate (n = 60) and severe (n = 27) groups according to WHO classification for anemia and parasite burden. Serum triglycerides were assayed in VL groups along with controls (n = 37). RESULTS: Serum triglyceride level was significantly higher in VL than controls [mean values were 173.50 ± 47.67 versus 127.1 ± 53.79 mg/dl, respectively (p < 0.0001)]. Triglyceride level was significantly higher in severe than in mild/moderate group of VL [211.3 ± 50.2 mg/dl versus 134 ± 45.09 mg/dl, respectively (p < 0.0001)]. Hypertriglyceridemia (>161.7 mg/dl) was noted in all severe VL patients, compared to 31.66% of mild or moderate group (p < 0.0001). There was no significant difference between mild/moderate VL and controls. CONCLUSIONS: It is hypothesized that hypertriglyceridemia could be of additional diagnostic benefit to assess the probability and severity of VL in endemic areas.

Exploring the gold mine: [Au]-catalysed transformations of enynals, enynones and enynols.

Gold catalysed synthesis of carbo-/hetero-cyclic compounds is currently a topic of intense activity thanks to the unique properties bestowed upon gold by relativistic effects, the potential of which has been realised mainly during the past two decades. This review will dwell upon the reactions involving gold catalysis in which enynal, enynone or enynol is one of the reacting partners. Most often these reactions lead to fused hetero-/homo-cycles under mild conditions with environmentally benign byproducts. Thus an opportunity for the organic community to develop new methodologies, efficient asymmetric variants, and application in total synthesis by [Au]-catalysis has emerged.

Pattern of clinical benign euthyroid goitre in a tertiary care center in the Central Province of Sri Lanka from 1981-2011

Objectives: To describe the pattern of clinical euthyroidgoitre in a tertiary care unit in Sri Lanka before and after iodination of salt in Sri Lanka. Methods: We reviewed our thirty-one year computerised database of patients with goitres, spanning iodination in 1995. Results: Prevalence of euthyroid clinical simple diffuse goitre did not reduce during the first thirteen years (p=0.822). However, it reduced in the latter four years from 2008 to 2011. There is significant reduction of prevalence in the younger age groups (p<0.001). A significant reduction of nodular change was observed in all groups within seven years after iodination (p<0.001). Conclusions: There was a significant reduction in the prevalence of clinical nodularity in the post-iodination era in all age groups. Reduction in prevalence of clinical euthyroid simple diffuse goitre was observed only during the period 2008-2011.

Computed tomography-guided preoperative localization of abdominal wall endometrioma.

A multiparous obese patient with prior abdominal surgeries complained of cyclic abdominal pain located near the surgical scar. A 1 cm lesion was identified on imaging. Computed tomography-guided needle localization was performed immediately before surgery. This allowed for complete excision of the abdominal wall endometrioma and resolution of the cyclic, focal abdominal pain.

Divergence in the reactivity between amine- and phosphine-catalyzed cycloaddition reactions of allenoates with enynals: one-pot gold-catalyzed synthesis of trisubstituted benzofurans from the [3 + 2] cycloadduct via 1,2-alkyl migration and dehydrogenation.

Regioselective synthesis of functionalized dihydropyran derivatives by DABCO-catalyzed [2 + 4] cycloaddition of allenoates with enynals or enynones has been developed. Phosphine-catalyzed [3 + 2] cycloaddition of allenoates with enynals provides 1,1-alkyne (aldehyde)-substituted cyclopentenes wherein enynals act as electrophiles. These alkyne-tethered cyclopentenes upon [Au]/[Ag] catalysis lead to substituted benzofurans via 1,2-alkyl migration and dehydrogenation (aromatization). One-pot reaction of allenoates with enynals using sequential phosphine and gold catalysis is also reported. The cyclopentene obtained from the PPh3-catalyzed reaction of allenoate H2C═C═CH(COO-t-Bu) with enynal undergoes decarboxylation under the [Au]/[Ag] catalysis and forms a carboxylate-free benzofuran. The structures of key products are confirmed by single-crystal X-ray analysis.

Synthesis, Characterization, Fluorescence, Photocatalytic and Antibacterial Activity of CdS Nanoparticles Using Schiff Base.

Cadmium sulfide nanoparticles (CdS NPs) were successfully prepared using sonochemical method by employing Schiff-base, (2-[(4-methoxy-phenylimino)-methyl]-4-nitro phenol) as a complexing agent. Here, SB is used as a ligand to control the morphology of NPs. XRD patterns and TEM images show that the synthesized CdS NPs have cubic structures with a diameter of about 2-10 nm. The formation of CdS NPs and their optical, structure, thermal and morphologies were studied by means of UV-vis DRS, fluorescence, FTIR, zeta potential, XRD, SEM and TEM. The interactions between CdS NPs and SB were investigated in an aqueous solution using fluorescence spectroscopy. The fluorescence quenching studies suggest that SB quenches the fluorescence of CdS NPs effectively. The degradation kinetics of methyl red (MR) by the photocatalyst was followed by Langmuir-Hinshelwood model. The results revealed that photocatalytic degradation of MR by SB capped CdS NPs could be considered as a practical and reliable technique for the removal of environmental pollutants. The antibacterial activity of samples was evaluated against E. coli, S. aureus and P. aeruginosa and the results were compared. SB and SB capped CdS NPs could be a potential antibacterial compounds after further investigation.

Intracellular concentration of the tyrosine kinase inhibitor imatinib in gastrointestinal stromal tumor cells.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm in the gastrointestinal tract. In most GISTs, the underlying mechanism is a gain-of-function mutation in the KIT or the PDGFRA gene. Imatinib is a tyrosine kinase inhibitor that specifically blocks the intracellular ATP-binding sites of these receptors. A correlation exists between plasma levels of imatinib and progression-free survival, but it is not known whether the plasma concentration correlates with the intracellular drug concentration. We determined intracellular imatinib levels in two GIST cell lines: the imatinib-sensitive GIST882 and the imatinib-resistant GIST48. After exposing the GIST cells to imatinib, the intracellular concentrations were evaluated using LC-MS (TOF). The concentration of imatinib in clinical samples from three patients was also determined to assess the validity and reliability of the method in the clinical setting. Determination of imatinib uptake fits within detection levels and values are highly reproducible. The GIST48 cells showed significantly lower imatinib uptake compared with GIST882 in therapeutic doses, indicating a possible difference in uptake mechanisms. Furthermore, imatinib accumulated in the tumor tissues and showed intratumoral regional differences. These data show, for the first time, a feasible and reproducible technique to measure intracellular imatinib levels in experimental and clinical settings. The difference in the intracellular imatinib concentration between the cell lines and clinical samples indicates that drug transporters may contribute toward resistance mechanisms in GIST cells. This highlights the importance of further clinical studies to quantify drug transporter expression and measure intracellular imatinib levels in GIST patients.

Post-hysterectomy dyspareunia.

When appropriately performed, hysterectomy most often contributes substantially to quality of life. Postoperative morbidity is minimal, in particular after minimally invasive surgery. In a minority of women, pain during intercourse is one of the more long-lasting sequelae of the procedure. Complete evaluation and treatment of this complication requires a thorough understanding of the status and function of neighboring organ systems and structures (urinary system, gastrointestinal tract, and pelvic and hip muscle groups). Successful resolution of dyspareunia often may be facilitated with review of the patient's previous degree of comfort during sex and the nature of her relationship with her partner. Repeat surgery is needed in a small minority of patients.

Disability-adjusted life years due to leptospirosis in Monaragala District of Sri Lanka.

Leptospirosis is a zoonotic infection with significant morbidity and mortality. As an occupational disease, it has become a global concern due to its disease burden in endemic countries and rural areas. The aim of this study was to assess disease burden in terms of Disability-adjusted life years (DALYs) of leptospirosis.A hospital-based descriptive cross-sectional study was conducted using 450 clinically diagnosed leptospirosis patients admitted to base and above hospitals in Monaragala District, Sri Lanka, using a pre-tested interviewer-administered questionnaire. The patients were followed up until normal day-to-day life after discharge. Estimation of DALYs was done using laboratory-confirmed leptospirosis patients. Leptospirosis disease burden in Monaragala District was 44.9 DALYs per 100,000 population, which includes 33.18 Years of life losts and 10.9 YLDs. The incidence of leptospirosis in Monaragala District during the study period was 59.8 per 100,000 population, and the case fatality rate (CFR) was 1.5% and 75% of deaths were among males.The disease burden of leptospirosis in Monaragala District was significantly high and urgent efforts to control and prevent leptospirosis should be a priority.

Analysis of tryptophan metabolites and related compounds in human and murine tissue: development and validation of a quantitative and semi-quantitative method using high resolution mass spectrometry.

This study explores the metabolic differences between human and murine plasma in addition to differences between murine subcutaneous and visceral white adipose tissue. A quantitative and semi-quantitative targeted method was developed and validated for this purpose. The quantitative method includes tryptophan and its metabolites in addition to tyrosine, phenylalanine, taurine, B vitamins, neopterin, cystathionine and hypoxanthine. While the semi-quantitative method includes; 3-indoleacetic acid, 5-hydroxyindoleacetic acid, acetylcholine, asymmetric dimethylarginine, citrulline and methionine. Sample preparation was based on protein precipitation, while quantification was conducted using ultrahigh-performance liquid chromatography coupled to a quadrupole Orbitrap tandem mass spectrometer with electrospray ionization in the parallel reaction monitoring (PRM) mode. The low limit of quantification for all metabolites ranged from 1 to 200 ng mL-1. Matrix effects and recoveries for stable isotope labelled internal standards were evaluated, with most having a coefficient of variation (CV) of less than 15%. Results showed that a majority of the analytes passed both the intra- and interday precision and accuracy criteria. The comparative analysis of human and murine plasma metabolites reveals species-specific variations within the tryptophan metabolic pathway. Notably, murine plasma generally exhibits elevated concentrations of most compounds in this pathway, with the exceptions of kynurenine and quinolinic acid. Moreover, the investigation uncovers noteworthy metabolic disparities between murine visceral and subcutaneous white adipose tissues, with the subcutaneous tissue demonstrating significantly higher concentrations of tryptophan, phenylalanine, tyrosine, and serotonin. The findings also show that even a semi-quantitative method can provide comparable results to quantitative methods from other studies and be effective for assessing metabolites in a complex sample. Overall, this study provides a robust platform to compare human and murine metabolism, providing a valuable insight to future investigations.

Prophylactic strategies in recurrent vulvovaginal candidiasis: a 2-year study testing a phytonutrient vs itraconazole.

The aim of the present study was to assess the clinical efficacy of a one week/month treatment with a phytocompound with antimycotic properties (K-712, with following 100 mg composition: 10 mg of oleoresin from Pseudowintera colorata at 30 percent concentration in Polygodial together with trace amounts of Olea europea) in recurrent vulvo-vaginal candidiasis (RVVC), as compared to once a week treatment with an azole drug for 24 months follow up. This prospective randomized study involving 122 women (19 to 63 years old) with a history of proven episodes of RVVC in the prior 12 months. Patients were allocated in two treatment groups of 61 patients each and given A) Itraconazole 200 mg orally once a week or B) 1 tab twice a day of K-712 for one week/month. Each treatment schedule was well tolerated with 19 patients in the azole group complaining of transient mild symptoms (nausea, abdominal discomfort, unpleasant taste), while only 3 patients on K-712 reported slight dyspepsia. The number of relapses was significantly lower in the K-712-treated group as compared to the itraconazole-group (22 vs 39, p less than 0.05). Moreover, the former group showed a significantly decreased number of cases resistant or dose-dependent susceptible as compared to group A (p less than 0.05 vs itraconazole) and the same occurred for the occurrence of non-albicans species (group A 64.1 percent vs group B 31.8 percent, p less than 0.05). The overall mycological cure at the end of the 2-year study showed a comparable benefit between the two groups. From these data it appears that the present antifungal phytonutrient is equally effective as itraconazole in the overall treatment of RVVC over a 2-year follow-up, but yielding a significantly better prophylactic effect and also maintenance benefit with lower relapse rate, antifungal susceptibility and growth of azole-resistant species.