Deferasirox is a new oral iron chelator. It is the first oral iron chelator approved in USA by FDA for transfusion-dependent patients above 2 years suffering from severe chronic iron overload. It is also recommended as the initial therapy for patients over the age of 6 years who are suffering from beta-thalassaemia. The clinical study is developing in China. This review focuses the related studies and the latest progression about deferasirox. The phase II and III clinical trials and pharmacokinetics indicated that deferasirox is a safety and effective oral iron chelator, can significantly decrease the myocardial and hepatic iron load, also is easy to accept for patients. The common adverse reactions are gastrointestinal symptom and rash. But it was recently reported that deferasirox has some rare adverse events to which we must attach importance, especially for the special people. Besides the patients with chronic iron overload resulting from blood transfusions (transfusional hemosiderosis), the drug is also used for the patients who has accepted auto-SCT or suffered from reversible renal inadequacy caused by Fanconi syndrome. The standard dosage is not useful to every patient. The clinician should adjust dosage based on the patient's condition and related indexes. The serum ferritin is not one and reliable index to monitoring the effect and adjust the dosage. Otherwise, this review recommends some new characters of deferasirox, e.g. anti-fungus, anti-cell proliferation and so on.
Benzoates ; administration & dosage ; Clinical Trials as Topic ; Humans ; Iron Chelating Agents ; administration & dosage ; Triazoles ; administration & dosage

Androstadienes ; therapeutic use ; Antineoplastic Agents, Hormonal ; administration & dosage ; Aromatase Inhibitors ; administration & dosage ; Breast Neoplasms ; drug therapy ; Drug Administration Schedule ; Female ; Humans ; Nitriles ; administration & dosage ; Postmenopause ; Triazoles ; administration & dosage

OBJECTIVETo investigate the effect of two different doses of letrozole in promoting ovulation in infertile women with polycystic ovarian syndrome (PCOS).

METHODSSeventy-six PCOS infertile women undergoing intrauterine insemination (IUI) or with anovulation were divided into two groups and received oral letrozole at the daily dose of 2.5 (n=36) or 5.0 mg (n=40) from the 3rd to the 7th day of the menstrual cycle. Three days after discontinuation of the medication (the 10th day of the menstrual cycle ), ultrasound scanning was performed to monitor the follicle development. When the diameter of the biggest follicle reached 14 mm, the presence of luteinizing hormone (LH) was monitored; when LH positivity was detected, blood samples were drawn to test follicle-stimulating hormone (FSH), LH, estradiol (E2) and testosterone (T) levels. Human chorionic gonadotropin (hCG, 10 000 U) was then injected to induce ovulation.

RESULTSThe ovulation rate, stimulation follicle days, diameter of the biggest follicle on the day of LH positivity and the thickness of endometrium were all similar between the two groups (P>0.05). But in women receiving 5.0 mg letrozole, both the number of mature follicles and pregnancy rate were significantly higher than those in women having the half dose (P<0.05). The levels of FSH, LH, E2, and T on the third day of menstruation and on the day of HCG injection were similar between the two groups (P<0.05).

CONCLUSIONLetrozole at the dose of 5.0 mg/day produces higher pregnancy rate and more mature follicles in fertile women with PCOS.

Adult ; Aromatase Inhibitors ; administration & dosage ; Female ; Fertility Agents, Female ; administration & dosage ; Humans ; Infertility, Female ; drug therapy ; etiology ; Insemination, Artificial ; Nitriles ; administration & dosage ; Ovulation Induction ; methods ; Polycystic Ovary Syndrome ; complications ; Triazoles ; administration & dosage

OBJECTIVETo evaluate the inhibitory effect of genistin combined with anastrozole on the growth and apoptosis of breast tumor tissue, and to study their anti-cancer mechanism by using the model of 7,12-dimethylbenz [alpha] anthracene (DMBA)-induced mammary tumors following ovariectomy in Sprague-Dawley (SD) rats.

METHODSThe DMBA induced postmenopausal SD rats were randomly divided into the control group, the genistein group, the anastrozole group, and the genistein combined with anastrozole group. The growth of tumors was observed in each group. The proliferation index and apoptosis index of tumor cells were determined. Moreover, estradiol (E2) and 17beta-HSD1 mRNA levels were determined by ELISA and RT-PCR respectively.

RESULTSThe tumor growth was inhibited in the genistein group and the anastrozole group. The inhibitory ratio was significantly higher in the genistein combined with anastrozole group (P < 0.05). Compared with the control group, levels of E2 and 17beta-HSD1 mRNA decreased more significantly in the genistein combined with anastrozole group (P < 0.05).

CONCLUSIONSGenistein could suppress the growth of mammary tumors in postmenopausal rats. It showed synergistic effect when combined with anastrozole, which resulted in reduced levels of E2 and 17beta-HSD1 mRNA. It had inhibitory effect on the growth of breast tumors.

17-Hydroxysteroid Dehydrogenases ; metabolism ; Animals ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Estradiol ; metabolism ; Female ; Genistein ; administration & dosage ; pharmacology ; Mammary Neoplasms, Experimental ; chemically induced ; pathology ; Nitriles ; administration & dosage ; pharmacology ; Ovariectomy ; Postmenopause ; Rats ; Rats, Sprague-Dawley ; Triazoles ; administration & dosage ; pharmacology

PURPOSE: To evaluate the efficacy of minimal stimulation using discretely administered gonadotropin combined with clomiphene citrate (CC) or letrozole (LTZ) for intrauterine insemination (IUI) cycles. MATERIALS AND METHODS: Total 257 IUI cycles from 158 infertile couples were assessed. A CC dose of 100 mg/day (n=126 cycles) or a LTZ dose of 5 mg/day (n=131 cycles) was administered on days 3-5 of the menstrual cycle for 5 days. Each group received human menopausal gonadotropin at a dose of 150 IU by two or three alternative day: CC combined with alternate-day regimen for 2 or 3 days (CC+300, n=37; CC+450, n=89) and LTZ combined with alternate-day regimen for 2 or 3 days (LTZ+300, n=36; LTZ+450, n=95). RESULTS: The clinical pregnancy rate was comparable between the CC and LTZ groups (18.3% vs. 13.0%, p=0.243). The clinical pregnancy rate also showed no significant difference among the 4 groups (21.6% vs. 16.9% vs. 11.1% vs. 12.6%, p=0.507). The multiple pregnancy rate was significantly higher in LTZ compared to CC group (37.5% vs. 8.7%, p=0.028) and in the LTZ+450 compared to CC+450 group (50% vs. 13.3%, p=0.038). Overall, there were 15 cases of ovarian hyperstimulation syndrome (OHSS), with the prevalence being significantly lower in the LTZ compared to CC group (1.5% vs. 10.3%, p=0.003). OHSS was more prevalent in the CC+450 compared to the LTZ+450 group (12.4% vs. 1.1%, p=0.002). CONCLUSION: Our findings suggest that minimal stimulation using two alternate-day gonadotropin with LTZ decreases the development of OHSS and multiple pregnancies, while maintaining comparable pregnancy rates in IUI cycles.
Adult ; Aromatase Inhibitors/administration & dosage ; Clomiphene/*administration & dosage/therapeutic use ; Drug Administration Schedule ; Drug Combinations ; Female ; Fertility Agents, Female/administration & dosage/therapeutic use ; Fertilization in Vitro ; Gonadotropins/*administration & dosage ; Humans ; Infertility, Female/*drug therapy ; Insemination, Artificial/*statistics & numerical data ; Nitriles/*administration & dosage ; Ovulation Induction/methods/*statistics & numerical data ; Pregnancy ; Pregnancy Rate ; Treatment Outcome ; Triazoles/*administration & dosage

PURPOSE: To evaluate the efficacy of minimal stimulation using discretely administered gonadotropin combined with clomiphene citrate (CC) or letrozole (LTZ) for intrauterine insemination (IUI) cycles. MATERIALS AND METHODS: Total 257 IUI cycles from 158 infertile couples were assessed. A CC dose of 100 mg/day (n=126 cycles) or a LTZ dose of 5 mg/day (n=131 cycles) was administered on days 3-5 of the menstrual cycle for 5 days. Each group received human menopausal gonadotropin at a dose of 150 IU by two or three alternative day: CC combined with alternate-day regimen for 2 or 3 days (CC+300, n=37; CC+450, n=89) and LTZ combined with alternate-day regimen for 2 or 3 days (LTZ+300, n=36; LTZ+450, n=95). RESULTS: The clinical pregnancy rate was comparable between the CC and LTZ groups (18.3% vs. 13.0%, p=0.243). The clinical pregnancy rate also showed no significant difference among the 4 groups (21.6% vs. 16.9% vs. 11.1% vs. 12.6%, p=0.507). The multiple pregnancy rate was significantly higher in LTZ compared to CC group (37.5% vs. 8.7%, p=0.028) and in the LTZ+450 compared to CC+450 group (50% vs. 13.3%, p=0.038). Overall, there were 15 cases of ovarian hyperstimulation syndrome (OHSS), with the prevalence being significantly lower in the LTZ compared to CC group (1.5% vs. 10.3%, p=0.003). OHSS was more prevalent in the CC+450 compared to the LTZ+450 group (12.4% vs. 1.1%, p=0.002). CONCLUSION: Our findings suggest that minimal stimulation using two alternate-day gonadotropin with LTZ decreases the development of OHSS and multiple pregnancies, while maintaining comparable pregnancy rates in IUI cycles.
Adult ; Aromatase Inhibitors/administration & dosage ; Clomiphene/*administration & dosage/therapeutic use ; Drug Administration Schedule ; Drug Combinations ; Female ; Fertility Agents, Female/administration & dosage/therapeutic use ; Fertilization in Vitro ; Gonadotropins/*administration & dosage ; Humans ; Infertility, Female/*drug therapy ; Insemination, Artificial/*statistics & numerical data ; Nitriles/*administration & dosage ; Ovulation Induction/methods/*statistics & numerical data ; Pregnancy ; Pregnancy Rate ; Treatment Outcome ; Triazoles/*administration & dosage

Candidaemia associated with intravascular catheter-associated infections is of great concern due to the resulting high morbidity and mortality. The antibiotic lock technique (ALT) was previously introduced to treat catheter-associated bacterial infections without removal of catheter. So far, the efficacy of ALT against Candida infections has not been rigorously evaluated. We investigated in vitro activity of ALT against Candida biofilms formed by C. albicans, C. glabrata, and C. tropicalis using five antifungal agents (caspofungin, amphotericin B, itraconazole, fluconazole, and voriconazole). The effectiveness of antifungal treatment was assayed by monitoring viable cell counts after exposure to 1 mg/mL solutions of each antibiotic. Fluconazole, itraconazole, and voriconazole eliminated detectable viability in the biofilms of all Candida species within 7, 10, and 14 days, respectively, while caspofungin and amphotericin B did not completely kill fungi in C. albicans and C. glabrata biofilms within 14 days. For C. tropicalis biofilm, caspofungin lock achieved eradication more rapidly than amphotericin B and three azoles. Our study suggests that azoles may be useful ALT agents in the treatment of catheter-related candidemia.
Amphotericin B/administration & dosage/pharmacology ; Antifungal Agents/*administration & dosage/pharmacology/therapeutic use ; Biofilms/*drug effects ; Candida albicans/*drug effects/physiology ; Candida glabrata/*drug effects/physiology ; Candida tropicalis/*drug effects/physiology ; Candidiasis/drug therapy ; Catheter-Related Infections/drug therapy ; Catheterization, Central Venous ; Drug Administration Routes ; Echinocandins/administration & dosage/pharmacology ; Fluconazole/administration & dosage/pharmacology ; Humans ; Itraconazole/administration & dosage/pharmacology ; Microbial Sensitivity Tests ; Pyrimidines/administration & dosage/pharmacology ; Triazoles/administration & dosage/pharmacology

We describe two patients with fungal keratitis refractory to standard antifungal therapy whose conditions were managed with voriconazole. The first case is a patient with endophthalmitis and corneal ulcer due to Candida parapsilosis after receiving a corneal transplant. The patient was treated with amphotericin but showed no signs of improvement. Topical voriconazole, oral voriconazole, and intravitreal voriconazole yielded signs of improvement. The second case is a 63-year-old male who underwent a month of empiric treatment with 0.2% topical amphotericin for fungal keratitis but showed no signs of improvement. Treatment was then provided with 1% voriconazole. Both cases showed effective treatment with voriconazole. Voriconazole may be considered as a new method to treat fungal keratitis refractory to standard antifungal therapy.
Administration, Oral ; Antifungal Agents/*administration & dosage ; Candidiasis/diagnosis/*drug therapy/microbiology ; Cornea/microbiology/pathology ; Diagnosis, Differential ; Dose-Response Relationship, Drug ; Eye Infections, Fungal/diagnosis/*drug therapy/microbiology ; Follow-Up Studies ; Humans ; Keratitis/diagnosis/*drug therapy/microbiology ; Male ; Middle Aged ; Ophthalmic Solutions ; Pyrimidines/*administration & dosage ; Triazoles/*administration & dosage

Invasive fungal sinusitis is a rare, severe disease, most commonly presenting in immunocompromised patients who have impaired neutrophil function or who have received long term immunosuppressive therapy. The gold standard for treatment has been wide surgical debridement, intravenous administration of antifungal agents such as amphotericin B (AMB), and correction of the underlying immunocompromised state. A 51-year-old female was admitted to our hospital with fever and headache who had received renal transplantation 14 years ago in the other hospital. Paranasal sinus CT scan revealed hyperplasia and soft tissue density of the left maxillary sinus. Histological examination of the fungus ball and edematous mucosa of the left maxillary sinus revealed suspicious invasion of Aspergillus in the mucosa. Clinical improvement occurred after a combination of surgery and post-operative systemic antifungal therapy with voriconazole. We think that voriconazole as initial treatment may be initiated for invasive sinonasal aspergillosis, if the infection is known to be due to Aspergillus species.
Administration, Intravenous ; Amphotericin B ; Antifungal Agents ; Aspergillosis ; Aspergillus ; Debridement ; Female ; Fever ; Fungi ; Headache ; Humans ; Hyperplasia ; Immunocompromised Host ; Kidney ; Kidney Transplantation ; Maxillary Sinus ; Middle Aged ; Mucous Membrane ; Neutrophils ; Paranasal Sinuses ; Pyrimidines ; Sinusitis ; Triazoles

Adolescent ; Adult ; Aged ; Antifungal Agents ; therapeutic use ; Drug Therapy, Combination ; Echinocandins ; administration & dosage ; therapeutic use ; Female ; Hematologic Neoplasms ; drug therapy ; microbiology ; Humans ; Lipopeptides ; Male ; Middle Aged ; Mycoses ; drug therapy ; Pyrimidines ; administration & dosage ; therapeutic use ; Treatment Outcome ; Triazoles ; administration & dosage ; therapeutic use ; Voriconazole ; Young Adult