Hormone Preparations Research Articles

Preparation and characterization of recombinant human growth hormone–Zn2+-dextran nanoparticles using aqueous phase–aqueous phase emulsion

An effective and simple method was developed to prepare spherical and uniform-sized recombinant human growth hormone (rhGH)–Zn2+-dextran nanoparticles (NPs) for a variety of delivery applications of the delicate protein. The results showed that the prepared rhGH-Zn2+-dextran particles were spherical, glassy, and uniform in size. rhGH recovered from the NPs maintained its structural integrity and its bioactivity well, as suggested by the Nb2-11 cell proliferation assay. Using polyethylene glycol and polysaccharide to mediate Zn2+-induced precipitation has proved to be a promising method to prepare spherical protein-loaded NPs with desired sizes and preserved protein stability. From the Clinical EditorThis basic science paper discusses a simple yet effective method to prepare spherical and uniform-sized recombinant human growth hormone (rhGH)-Zn2+-dextran nanoparticles for a variety of delivery applications.

Menorrhagia and bleeding disorders in adolescent females

In women, von Willebrand disease (VWD) is the most common inherited bleeding disorder. Since VWD and other inherited bleeding disorders are autosomal disorders, they affect women and men. Menorrhagia, or heavy menstrual bleeding (HMB), is the most common symptom of women with bleeding disorder experience. Objectively, it is defined as bleeding that lasts for more than seven days or results in the loss of more than 80 ml of blood per menstrual cycle. The prevalence of menorrhagia in a woman with a bleeding disorder ranges from 32 to 100% in patients with VWD, from 5 to 98% in patients with a platelet dysfunction and from 35 to 70% in women with a rare factor deficiency. A detailed history and a careful physical exam are the first steps towards a diagnosis in adolescents, adding a PBAC>100 increased the sensitivity of the screening tool further to 95%. Laboratory testing should be made at the time of menstrual bleeding in an effort to capture the lowest level of VWF:Ag and FVIII:C. Treatment options for menorrhagia in VWD: (1) antifibrinolytic therapy with tranexamic acid, (2) the non-transfusional agent desmopressin (DDAVP), (3) purified blood products that contain factor VIII and VWF concentrated from plasma and (4) hormonal preparations.

Comparative efficacy of different CIDR protocols for the treatment of postpartum anestrous in Iraqi buffaloes

The aim of this study was to evaluate and compare the efficacy of different CIDR protocols including some hormonal preparations for the treatment of postpartum anestrous of Iraqi northern buffaloes. The present study was conducted on 70 anestrous buffaloes suffering from postpartum ovarian inactivity. Buffaloes were randomly assigned to three treatment groups. Buffaloes in Treatment 1 (n=20) injected on day 0 of the experiment, GnRH 250 ig and a CIDR was placed in the anterior vagina. On day 7, they were injected with 25 mg of PGF2a and on the following day (day 8) the CIDR were removed. On day 9 a second dose of GnRH (250 ig) was injected. Buffaloes in Treatment 2 (n=20) received on day 0 GnRH (250 ig) and a CIDR were placed in the anterior vagina. On day 7, CIDR were removed and injected with GnRH (250 ig). Treatment 3 (n=20) on day 0 a CIDR were placed in the anterior vagina. On day 6, they were injected with 1000 IU of eCG. CIDR were removed on day 7 and injected with GnRH (250 ig). A control group (n=10) received no treatments. Results showed that in 8days treatment 1 (GnRH+CIDR— —7 PGF a+9 GnRH), 15 out of 20 buffaloes received treatment exhibited estrus 2 within 69.4 ± 8.4 h after CIDR removal. The estrus induction rate was 75%. Total number of buffaloes became 7 days pregnant was 4 (26.7%). In treatment 2 (GnRH+CIDR— —GnRH), 65% of the buffaloes received treatment exhibited estrus within 77.8 ± 5.6 h after CIDR removal. Total number of buffaloes became pregnant was 4 7 days (26.7%). In treatment 3 (CIDR— — 6 eCG+7 GnRH), 100% of the buffaloes received treatment exhibited estrus within 78.3 ± 11.8 h after CIDR removal. In conclusion, our results indicate that the addition of GnRH and eCG to a progesterone-based CIDR protocol substantially improves the estrus induction and pregnancy rates in postpartum anestrous buffaloes.

Contraception for the HIV-positive woman: a review of interactions between hormonal contraception and antiretroviral therapy.

Background. Preventing unintended pregnancy in HIV-positive women can significantly reduce maternal-to-child HIV transmission as well as improve the woman's overall health. Hormonal contraceptives are safe and effective means to avoid unintended pregnancy, but there is concern that coadministration of antiretroviral drugs may alter contraceptive efficacy. Materials and Methods. We performed a literature search of PubMed and Ovid databases of articles published between January 1980 and February 2012 to identify English-language reports of drug-drug interactions between hormonal contraceptives (HCs) and antiretroviral drugs (ARVs). We also reviewed the FDA prescribing information of contraceptive hormone preparations and antiretrovirals for additional data and recommendations. Results. Twenty peer-reviewed publications and 42 pharmaceutical package labels were reviewed. Several studies of combined oral contraceptive pills (COCs) identified decreased serum estrogen and progestin levels when coadministered with certain ARVs. The contraceptive efficacy of injectable depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) were largely unaffected by ARVs, while data on the contraceptive patch, ring, and implant were lacking. Conclusions. HIV-positive women should be offered a full range of hormonal contraceptive options, with conscientious counseling about possible reduced efficacy of COCs and the contraceptive implant when taken with ARVs. DMPA and the LNG-IUS maintain their contraceptive efficacy when taken with ARVs.

Misconception and Concerns about Bioidentical Hormones Used for Custom-Compounded Hormone Therapy

The results of the Women’s Health Initiative hormone therapy (HT) trials have caused both apprehension and confusion about the overall risks and benefits associated with postmenopausal HT (1). Since the results were published, patient and clinician interest in potential alternatives to conventional HT has grown immensely and continues to grow. This appears to be particularly true for products or regimens that claim to have fewer risks and side effects than commercially available HT preparations. One commonly used alternative HT involves customcompounded hormone preparations. The hormones in these preparations include estrogen [17 -estradiol (estradiol), estrone, and/or estriol], progesterone, testosterone, androstenedione, and dehydroepiandrosterone. The products can be prepared in individualized dosages and forms such as creams, gels, lotions, sublingual tablets, troches (lozenges) for buccal administration, and suppositories by compounding pharmacies from a clinician’s prescription. They are often touted by advocates as safer than commercially prepared HT products. Proponents also claim that customcompounded HT is associated with fewer side effects and may provide better symptom relief than conventional HT because the hormones used in the preparations are “bioidentical,” i.e. identical to those made in the body. The majority of these claims are unsubstantiated, and no rigorous randomized control trials have been carried out to support any of the claims. Because the customcompounding of HT products is not regulated, a particular concern is that some women may be overdosed, or treated with ineffective products, or subject to unidentified risk. The objectives of the present commentary are: 1) to show that the so-called “bioidentical” hormones in custom-compounded HT preparations may not be identical to those made in the body; and 2) to point out how the lack of regulation of these hormone products can cause adverse effects in postmenopausal women using them.

Three-Year Efficacy and Safety of LB03002, a Once-Weekly Sustained-Release Growth Hormone (GH) Preparation, in Prepubertal Children with GH Deficiency (GHD)

GH treatment currently requires daily sc injections, resulting in suboptimal compliance. A GH regimen with fewer injections may offer patients and caregivers a less arduous option. LB03002 is a novel sustained-release GH formulation for once-weekly dosing. GH-deficient, GH-naive prepubertal children were randomized to four groups who received 0.2 mg/kg/wk LB03002 for 12 months, followed by 0.5 mg/kg/wk for another 24 months (n=13); 0.5 mg/kg/wk LB03002 for 36 months (n=13); 0.7 mg/kg/wk LB03002 for 12 months, followed by 0.5 mg/kg/wk for another 24 months (n=13); or daily GH 0.03 mg/kg/d for 24 months, switched to 0.5 mg/kg/wk LB03002 for 12 months (n = 12). Height velocity increased in all groups; the increase was less for the 0.2 mg/kg/wk LB03002 group at 12 (P = 0.008) and 24 months (P = 0.030), with no statistically significant differences at any time for the 0.5 mg/kg/wk and 0.7 mg/kg/wk LB03002 groups, vs. daily GH. Height sd score gain at 12 months was significantly (P = 0.023) less for the 0.2 mg/kg/wk group (1.05 ± 0.38) than daily GH (1.47 ± 0.29), but with no statistically significant difference for the 0.5 mg/kg/wk (1.37 ± 0.39) and 0.7 mg/kg/wk (1.50 ± 0.44) LB03002 groups vs. daily GH. There were no significant differences in height sd score gain between any groups at 24 and 36 months. Bone maturation did not differ for any LB03002 dose compared with daily GH. Serum IGF-I concentrations increased as expected, with no long-term differences between groups. Mean fasting glucose and glycosylated hemoglobin concentrations did not exceed normal ranges for any treatment group at any time. LB03002 at doses of 0.5 mg/kg/wk and 0.7 mg/kg/wk was shown to be effective and safe with once-weekly dosing in GH-deficient children, and 0.5 mg/kg/wk LB03002 was chosen as the optimal dose for long-term assessment.

Acupuncture Might Have Contributed to Improving Amenorrhoea in a Top Athlete

A 26-year-old top female athlete (height 157 cm), who took part in competitive sport similar to middle- and long-distance running, became amenorrhoeic in February 2009. In late May 2009, athletic amenorrhoea was diagnosed and a norgestrel-ethinyl estradiol combination (norgestrel 0.5 mg and ethinyl estradiol 0.05 mg three times daily) was prescribed for 2 weeks. She experienced menstrual bleeding on one occasion for 4 days in mid-June before becoming amenorrhoeic again. The athlete visited our centre to try acupuncture treatment. Forty-six acupuncture sessions were given between 1 October 2009 and 2 November 2010. Acupuncture point selection was based on classical acupuncture medicine and included points long used for gynaecological disorders in Japan--namely, CV6, CV12, LR3, LR14, BL17, BL18, BL23, SP6 and SP10. On 7 May 2010, owing to lack of regular normal vaginal bleeding, she again consulted her gynaecologist and was prescribed the same hormone preparation as used previously. She took it for 2 weeks in conjunction with acupuncture treatment. From July, the amount and duration of menstrual flow increased at regular intervals. Throughout July, a biphasic pattern in basal body temperature (BBT) was gradually established. In conclusion, the single hormone replacement therapy in May 2009 without acupuncture treatment was not effective for the amenorrhoea, nor was the single acupuncture treatment between October 2009 and May 2010. However, after hormone replacement therapy was started in May 2010 in conjunction with regular acupuncture treatment, menstrual blood flow restarted and BBT moved close to the biphasic pattern.

Recombinant or Urinary Human Chorionic Gonadotropin in Ovulation Induction?

Recombinant or Urinary Human Chorionic Gonadotropin in Ovulation Induction?

Secondary amenorrhea in a woman with spinocerebellar degeneration treated with thyrotropin-releasing hormone: a case report and in vitro analysis

IntroductionWhile thyrotropin-releasing hormone is known to be a prolactin-release stimulating factor, thyrotropin-releasing hormone-tartrate and its derivative, taltirelin hydrate, are used for the treatment of spinocerebellar degeneration, a degenerative disease characterized mainly by motor ataxia. We report the case of a patient being treated with a thyrotropin-releasing hormone preparation for spinocerebellar degeneration who developed amenorrhea after a dose increase. Her hormonal background was analyzed and the effect of prolonged exposure to thyrotropin-releasing hormone on pituitary prolactin-producing cells was examined in vitro.Case presentationOur patient was a 36-year-old Japanese woman who experienced worsening of gait disturbance at around 23 years of age, and was subsequently diagnosed as having spinocerebellar degeneration. She had been treated with thyrotropin-releasing hormone-tartrate for four years. Taltirelin hydrate was added to the treatment seven months prior to her presentation, followed by an improvement in gait disturbance. Around the same period, she started lactating and subsequently developed amenorrhea three months later. Taltirelin hydrate was discontinued and she was referred to our hospital. She was found to have normal sex hormone levels. A thyrotropin-releasing hormone provocation test showed a normal response of thyroid-stimulating hormone level and an over-response of prolactin at 30 minutes (142.7 ng/mL). Resumption of menstruation was noted three months after dose reduction of thyrotropin-releasing hormone. In our in vitro study, following long-term exposure to thyrotropin-releasing hormone, cells from the rat pituitary prolactin-producing cell line GH3 exhibited an increased basal prolactin promoter activity but showed a marked decrease in responsiveness to thyrotropin-releasing hormone.ConclusionsPhysicians should be aware of hyperprolactinemia-associated side effects in patients receiving thyrotropin-releasing hormone treatment. Long-term treatment with a thyrotropin-releasing hormone preparation might cause a large amount of prolactin to accumulate in prolactin-producing cells and be released in response to exogenous thyrotropin-releasing hormone stimulation.

A cardiovascular safety study of LibiGel (testosterone gel) in postmenopausal women with elevated cardiovascular risk and hypoactive sexual desire disorder

Evaluation of the safety of hormonal preparations for the treatment of female sexual dysfunction is important to assess the benefit-to-risk profile of these drugs and has been strongly encouraged by the Food and Drug Administration. LibiGel (Biosante Pharmaceuticals, Inc., Lincolnshire, IL), a low-dose testosterone gel, is under development for the treatment of hypoactive sexual desire disorder (HSDD) in oophorectomized women. To evaluate the long-term effects of LibiGel on risk for cardiovascular (CV) events, breast cancer, and general safety, a randomized, placebo-controlled clinical study using a novel adaptive design to optimize sample size and power is being conducted. The primary end point of the BioSante LibiGel Safety Study (BLISS) is a composite of CV events including death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, hospitalized unstable angina, and venous thromboembolic events. Breast cancer is a coprimary end point. Postmenopausal women (both surgically and naturally) with HSDD and increased risk for CV events will be followed up for up to 5 years postrandomization with an interim data analysis for regulatory approval after the last woman enrolled has been on therapy for at least 12 months. Determination of the number of subjects to enroll is based on an adaptive design that uses interim data to estimate the predictive probability of study success. In agreement with the Food and Drug Administration, LibiGel will be declared safe if the upper limit of the 97.2% CI of the hazard ratio is ≤2.0 or the upper bound of the 97.2% CI for the absolute difference between CV event rates per 100 person-years is ≤1% and the observed hazard ratio is ≤2.0. The BLISS study will define the CV safety profile of low-dose testosterone therapy in the formulation of LibiGel for postmenopausal women with HSDD, and the trial design may provide a paradigm for studies that aim to document long-term safety when the proposed outcome under study is an uncommon adverse event.

Effect of two follicle stimulating hormone (FSH) preparations and simplified superovulatory treatments on superovulatory response in Xinji fine-wool sheep

The objective of the present study was to investigate the response of Xinji fine-wool sheep to superovulation with two follicles stimulating hormone (FSH) preparations and simplified superovulatory treatments. In Experiment I, 22 adult Xinji fine-wool sheep were randomly allocated in equal number (n = 11) to two groups which were superovulated with 280 IU FSH-P and 150 mg Folltropin-V, respectively. In Experiment II, 61 adult Xinji fine-wool sheep randomly divided into four groups were treated with four different superovulatory schemes based on the dosage and number of Folltropin-V injection, respectively. The ewes in the four groups were treated with a total of 150 mg Folltropin-v (6 injection, Group A, n = 15), 120 mg Folltropin-V (3 injection, Group B, n = 18), 90 mg Folltropin-V (3 injection, Group C, n = 13) and 150 mg Folltropin-V dissolved in 30% PVP (1 injection, Group D, n = 15), respectively. The results show that the number of corpora lutea was significantly higher in ewes treated with Folltropin-V than that with FSH-P (P 0.05). However, the number of recovered embryos and transferable embryos in Groups C and D is significantly lower than those in Groups A and B (P<0.05). In conclusion, superovulation with 120 mg Folltropin-V (3 injections) is the most appropriate superovulatory treatment in Xinji fine-wool sheep. Key words : Superovulatory response, follicle stimulating hormone (FSH) preparations, Xinji fine-wool sheep.

Effect of two follicle stimulating hormone (FSH) preparations and simplified superovulatory treatments on superovulatory response in Xinji fine-wool sheep

Effect of two follicle stimulating hormone (FSH) preparations and simplified superovulatory treatments on superovulatory response in Xinji fine-wool sheep

Doping and Thrombosis in Sports

Historically, humans have long sought to enhance their "athletic" performance to increase body weight, aggressiveness, mental concentration and physical strength, contextually reducing fatigue, pain, and improving recovery. Although regular training is the mainstay for achieving these targets, the ancillary use of ergogenic aids has become commonplace in all sports. The demarcation between ergogenic aids and doping substances or practices is continuously challenging and mostly based on perceptions regarding the corruption of the fairness of competition and the potential side effects or adverse events arising from the use of otherwise unnecessary ergogenic substances. A kaleidoscope of side effects has been associated with the use of doping agents, including behavioral, skeletal, endocrinologic, metabolic, hemodynamic, and cardiovascular imbalances. Among the various doping substances, the most striking association with thrombotic complications has been reported for androgenic anabolic steroids (i.e., cardiomyopathy, fatal and nonfatal arrhythmias, myocardial infarction [MI], intracardiac thrombosis, stroke, venous thromboembolism [VTE], limb arterial thrombosis, branch retinal vein occlusion, cerebral venous sinus thrombosis) and blood boosting (i.e., VTE and MI, especially for epoetin and analogs). The potential thrombotic complication arising from misuse of other doping agents such as the administration of cortisol, growth hormone, prolactin, cocaine, and platelet-derived preparations is instead speculative or anecdotal at best. The present article provides an overview on the epidemiological association as well as the underlying biochemical and biological mechanisms linking the practice of doping in sports with the development of thrombosis.

Enhancing sensitivity and precision on NIR reflectance determination of an API at low concentration: Application to an hormonal preparation

The use of a mixed calibration sample set (intact production tablets and powdered doped samples used to enlarge calibration range) is a usual procedure for the NIR reflectance determination of the API content of a pharmaceutical solid preparation. However, the high difference in scattering properties and the intrinsic low sensitivity of NIR make difficult the achievement of a good precision when API is at a low mass proportion (≈1%, w/w). The compression of the calibration powdered samples has been studied as a very simple procedure to enhance the sensitivity of NIR reflectance measurements and, consequently, to improve precision. Different pretreatments (SNV, 1D, 2D and their combinations) have been applied to reduce the spectral difference between powdered and compressed samples. Although none eliminates completely this difference, the combined pretreatment SNV + 2D has proved to be the one with a better performance. Results obtained by using both calibration sample sets (powdered and compacted) in the quantification of estradiol valerate (VE, 2 mg/tablet, ≈1.6%, w/w) and medroxyprogesterone (MPA, 10 mg, ≈8%, w/w) in intact tablets of the hormonal preparation show that a slight but significant improvement in precision is obtained when using compacted samples for calibration. A HPLC procedure was developed to be used as reference method.

Duration of Endometrial Preparation and Hysteroscopic Sterilization Placement Success

Objective: Previous research has demonstrated the value of endometrial preparation before hysteroscopic procedures. Duration of endometrial preparation prior to hysteroscopic sterilization has not yet been evaluated. The aim of our study is to evaluate the relationship between hormonal endometrial preparation duration and the placement success rate with Essure hysteroscopic sterilization. Study Design: An institutional review board (IRB) approved retrospective cohort study of all women who underwent hysteroscopic sterilization from August 2003 to April 2010 in an urban academic center in Chicago, Illinois was performed. Exclusion criteria included insufficient or incomplete data. Variables including Essure placement success, type and duration of endometrial preparation, demographic factors and hysterosalpingogram (HSG) occlusion rates were compared using chi-square and co-relational analyses. Results: Overall, the Essure placement success rate was 91.5% (226/247). Race, parity, body mass index (BMI), previous surgical history and type of hormonal endometrial preparation did not significantly affect the placement success rate. Women with endometrial preparation (n=216) were significantly more likely to experience successful placement compared to those with no preparation (n=31; p<.005). When comparing Essure placement success rates in patients with 30 days or less (n=49) compared to those that underwent more than 30 days of preparation (n=167), there was no significant effect of duration of hormonal endometrial preparation on placement success rate (p=0.518). Conclusion: This study supports the use of hormonal endometrial preparation prior to hysteroscopic sterilization and suggests that the duration of hormonal treatment does not affect the rate of successful Essure placement. Therefore, scheduling patients for Essure procedures within 30 days of initiating endometrial preparation is unlikely to deleteriously affect Essure placement success, but may instead lower costs and improve patient compliance. Further prospective studies are needed to validate these findings.

The incidence of thyroid function abnormalities and natural course of subclinical thyroid disorders, Tehran, I.R. Iran.

Despite the high prevalence of thyroid dysfunction, the epidemiology and natural course of these disorders have not been identified yet. The present survey was conducted to determine the incidence of thyroid dysfunction and natural course of subclinical thyroid disorders in an urban community of Tehran, I.R. Iran. Serum TSH and thyroperoxidase antibody (TPOAb) were measured at baseline and after 6.7 yr from a sample of 1999 randomly selected subjects aged≥20 yr, participants of the Tehran Lipid and Glucose Study (TLGS). Median TSH value and 2.5, 5, 95, and 97.5 TSH percentiles were determined at baseline using data obtained from 808 negative TPOAb subjects with no history of any thyroid disease or surgery, goiter, nodule, taking thyroid hormone preparations or anti-thyroid drugs. In those with abnormal TSH level, total T4 and T3 uptake were measured and free T4 index was calculated. Normal TSH reference range was 0.4-5.8 μU/ml according to the 2.5 and 97.5 TSH percentiles. The incidence rates of thyroid function abnormalities in 1000 subjects per year were as follows: clinical hypothyroidism: 0.28 in women and 0.21 in men; subclinical hypothyroidism: 11.59 in women and 4.69 in men; clinical hyperthyroidism: 1.4 in women and 0.21 in men; and subclinical hyperthyroidism: 5.72 in women and 3.62 in men. A significant increase was found in the frequency of positive TPOAb in women from 15.9 to 17.7% (p=0.006). Of 8 women with subclinical hypothyroidism at baseline, 5 remained unchanged, 1 became normal, and 1 developed clinical hypothyroidism at followup. Two women with subclinical hyperthyroidism normalized at follow-up. Of 2 men with subclinical hypothyroidism at baseline, 1 remained unchanged, whereas the other progressed to clinical hypothyroidism. After a 6.7 yr follow-up significant increase in the incidence of subclinical thyroid disorders was observed in both men and women, as compared to overt thyroid dysfunction. Increase in the prevalence of TPOAb positivity was observed only in women.

Artificial reproduction of wild and cultured barbel (Barbus barbus, Cyprinidae) under controlled conditions

The aim of this work was to compare the effects of controlled reproduction of cultured and wild common barbel, Barbus barbus (L.). Preparations containing different GnRH analogues and dopamine receptor antagonists (Ovopel, Ovaprim) as well as human chorionic gonadotropin (hCG) (in the case of cultured fish) were applied and their influence on ovulation, spermiation and quality of gametes obtained was determined. No differences in the qualitative or quantitative parameters of semen were found between fish stimulated with different hormonal preparations and those not receiving hormonal stimulation. The high suitability of Ovaprim for ovulation induction in (cultured and wild) barbel was confirmed. The highest synchronisation of ovulation was obtained after the application of Ovopel (18 ± 3 h), but the best results of controlled reproduction (expressed as the percentage of ovulations and survival of embryos) were obtained by applying Ovaprim (83.2 ± 4.1). A significantly higher percentage of ovulation was obtained in cultured fish (80-90%) than in wild fish (< 25%).

1313 POSTER Stability of Diluted L-asparaginase in Normal Saline Solution

Background and purpose: Patient information pamphlets containing drug information are educational and improve knowledge on dosage, adverse effects, and drug interactions. These pamphlets are provided by pharmaceutical companies and are convenient and appropriate; they are provided free of cost. However, these pamphlets differ in content and the volume and quality of data provided for each drug. In this study, we researched the structure and content of pamphlets produced and distributed by pharmaceutical companies in Japan for chemotherapy drugs. Material and Method: We collected pamphlets for chemotherapy drugs at 96 components and 116 pharmaceutical drugs; pamphlets for generic drugs were not included in the study. These pamphlets had been produced and distributed between March 1962 and August 2010. We analyzed the pamphlets with regard to dosage form; mechanism of action; and total number of pages, i.e., volume of data. Results: There were published patient 74 information pamphlet of chemotherapy in 55 of the 116 drugs. The median number of content pages in the pamphlets was 31 (range, 6–101 pages). We obtained a total of 43 pamphlets for 30 of the 71 drugs in the injectable dosage form and 33 pamphlets for 25 of the 42 drugs in the oral dosage form. We obtained 41 pamphlets for 28 of the 77 drugs that had a cytotoxic mechanism of action, 25 pamphlets for 18 of the 21 molecular-targeted drugs and 8 pamphlets for 8 of the 8 hormone preparation. The content of adverse effects was included in all pamphlets. On the other hand, the content of coping strategies for the adverse effects was included 69% (51/74 pamphlets) of pamphlets. Especially, all pamphlets of the hormone preparation had no content of coping strategies for those. The content of coping strategies for those significantly correlated with the dosage form (p < 0.05) and mechanism of action (p < 0.001). Conclusion: Our results showed that the patient information pamphlets of chemotherapy were not enough published in Japan. The contents of the patient information pamphlets are expected to be included equally regardless of dosage form or mechanism of action. Therefore it would be required to accumulate and assess clinical information of adverse effects for chemotherapy agents, especially for molecular-targeted drugs, and to reflect in the patient information pamphlets of chemotherapy.

Validation of a simple RP-HPLC method developed for the quantification of meta-cresol in parathyroid hormones formulation

Aim: To develop and validate a rapid and sensitive reverse phase high performance liquid chromatography (RP-HPLC) method with UV detection for quantification of meta-cresol (m-cresol) in pharmaceutical preparation of parathyroid hormone (1–34) (PTH). Materials and Methods: Chromatography was performed on a Jupiter RP C-18 (4.6mm ID x 250mmL, porosity 300Å, particle size 5μm) with a guard column (reversed- phase C18 column of 4.6mm ID x 12.5mmL, porosity 300Å, particle size 5μm) using a mobile phase containing 0.1% TFA in 60% methanol with isocratic program at 1.0mL/ min flow rate. Detection was carried out at 217nm. The method was validated as per ICH guidelines for linearity (correlation coefficient = 0.99), range, accuracy, precision, and robustness (n = 9 during accuracy parameter whereas n =15 during linearity and range parameter and n = 6 during repeatability). Robustness was confirmed by considering two factors; âge effect of the mobile phase and test sample and with different columns during method development. Results : The method was linear over the concentration range of 75–120μg/mL. The precision of the method in terms of relative standard deviation was evaluated from intra- and inter-day replicate injections of system suitability standards of m-cresol using different equipment and different columns. Components of within-and between-batch variances were found to be below 2% (n = 30) and 3%, respectively, which constituted an acceptable level of variation. Retention time was found to be about 5.2min and 10.9min for m-cresol and PTH, respectively. Conclusion:The developed method thus has the potential of being useful for routine quality control of m-cresol.

Effect of hormonal compounds on embryogenesis of the pond snail Lymnaea stagnalis (L., 1758)

Effect of preparations ofa peptide nature (pituitrin and oxytocin) and of a steroid nature (progesterone and hydrocortisone) on embryonic development of freshwater gastropod Lymnaea stagnalis (Mollusca, Gastropoda, Pulmonata) is described. The hormonal preparations used, which differed in chemical nature and physiological activity, may render diverse effects on embryogenesis of the studied mollusk. Of neurohormones, pituitrin rendered the most noticeable and principally stimulating effect. Oxytocin was incorporated in regulatory processes much later and its effect on the rate of realization of particular stages depended more on the quality of occurring changes. In final stages of development, this hormone principally inhibited growth and development of embryos. The female sex hormone progesterone rendered an expressed stimulatory effect, especially notable in later developmental stages of embryos. The hormone hydrocortisone stimulated initial stages of embryogenesis. Its effect was almost not expressed in the final stages. The discovered differences seem to be related both to the functional specificity of the investigated compounds and to specific traits of mechanisms of realization of their effects. A hypothesis is formulated: in gastropods, similarly to vertebrates, the hormones are systemic embryonic and postnatal inducers of differentiation processes.