Long-term results with a long-acting formulation of D-TRP-6 LH-RH in patients with prostate cancer: an Italian prostatic cancer project (P.O.N.CA.P.) study

Ninety-five patients with stage C (C1 + C2) or D (D1 + D2) prostatic carcinoma were treated with the depot formulation of D-TRP-6 LH-RH ("Decapeptyl") for up to 33 months. Serum testosterone (T) levels were significantly reduced to castration levels within 4 weeks and maintained persistently low. Similarly, LH levels were decreased, although they remained in the normal range. Stimulation tests with either Gn-RH or HCG in course of treatment showed the achievement of a complete pituitary desensitization and almost a complete down-regulation of testicular LH receptors. Of 88 patients evaluable for response, about one-half showed an objective response. In most cases, subjective improvement with relief of bone pain and/or urinary symptoms was obtained without major side effects. These results indicate that the depot formulation of D-TRP-6 LH-RH offers an effective therapeutic alternative for patients with advanced prostatic cancer.     

GnRH antagonist versus follicular-phase single-dose GnRH agonist protocol in patients of normal ovarian responses during controlled ovarian stimulation

Objective: This study aims to explore the differences of the ovarian stimulation (OS) characteristics, laboratory, and clinical outcomes between follicular-phase single-dose gonadotropin-releasing hormone (GnRH) agonist protocol and GnRH antagonist protocol during controlled ovarian hyperstimulation (COH).

Methods: About 1883 consecutive IVF/ICSI fresh cycles of normal ovarian responders were retrospectively analyzed, with 1229 in the single-dose GnRH agonist protocol group and 654 in the GnRH antagonist protocol group at Reproductive Medical Center of Tongji Hospital from 1 January 2014 to 31 December 2017.

Results: The follicular-phase single-dose GnRH agonist group showed significantly more oocytes obtained, higher implantation rate and pregnancy rate, as well as lower luteinizing hormone (LH) level and estradiol (E2)/oocyte ratio on the day of human chorionic gonadotropin (hCG) administration. However, differences were not significant in meiosis II (MII) oocyte rate, two pronuclear zygote (2PN) embryo rate, viable embryo rate or high-quality embryo rate, compared with the GnRH antagonist group. Further comparison of clinical outcomes in the first frozen-thawed cycles did not show significant difference in either implantation or clinical pregnancy rate between the two protocol groups.

Conclusions: Follicular-phase single-dose GnRH agonist protocol may achieve better clinical outcomes in normal ovarian responders, which could be explained more by positive effect on endometrial receptivity rather than embryo quality.     

Thyroid function during the first year of use of the injectable contraceptive depot medroxyprogesterone acetate

Purpose: The aim of the study was to evaluate thyroid function profile as a possible factor influencing weight and body composition variation in new users of depot medroxyprogesterone acetate (DMPA).

Materials and methods: A prospective, non-randomised, comparative study was conducted at the University of Campinas, Brazil. Women aged 18–40 years with a body mass index (BMI) less than 30?kg/m², normal oral glucose tolerance test, no known diseases, and using no medication, who opted to use DMPA were paired by age (±1 year) and BMI (±1?kg/m²) with women initiating copper intrauterine device (IUD) use. The main outcome measures were thyroid function profile, weight, and body composition, as measured by dual-energy X-ray absorptiometry. We used repeated measures ANOVA to perform comparisons between times and groups.

Results: We evaluated 28 DMPA users and 24 IUD users who completed the 12-month follow-up. We observed that FT4 levels were higher at 12 months (compared to baseline) in the DMPA group (p?<?.0001) and that FT4/FT3 ratio had increased in both groups. Additionally, at 12 months, total body mass had increased around 2?kg and lean mass increased in the DMPA group compared to the IUD group; there was also an increase in weight, BMI, total body mass, and fat mass when compared to baseline.

Conclusions: No changes in thyroid function occurred that could explain the weight increase observed in DMPA users.     

那法瑞林埋植型长效制剂对大鼠子宫内膜异位的抑制作用

研究那法瑞林埋植型长效制剂单次应用对大鼠子宫内膜异位的作用及作用机制。采用手术方法建立大鼠模型,血清雌二醇（E2）、孕酮（Pg）水平和异位内膜雌激素受体（ER）、孕激素受体（PR）分别用酶免疫和亲和组化一步法检测。结果：那法瑞林长效制剂对异位内膜的抑制率（70．4±25．1）％接近去势组;血清E2和Pg的周期性分泌高峰消失;子宫和卵巢萎缩退化,重量减轻;异位内膜ER和PR阳性率也显著降低。结论：那法瑞林长效制剂对大鼠子宫内膜异位有显著抑制作用,低甾体激素水平是其主要作用机制。     

Role of crystallization in the phase inversion dynamics and protein release kinetics of injectable drug delivery systems

The role of polymer crystallization in the phase inversion dynamics and in vitro protein release kinetics of semi-crystalline poly (-caprolactone) and amorphous poly ( , -lactide) (PDLA) blend solutions has been examined using high performance liquid chromatography (HPLC), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) techniques. Varying the degree of crystallizability of the solutions led to the emergence of two general classes of depots. Depots with a high degree of crystallinity are characterized by porous morphologies indicative of solid–liquid (s–l) de-mixing and delayed burst release profiles. Alternatively, depots with a low degree of crystallinity are characterized by dense morphologies formed by mild liquid–liquid (l–l) phase separation and slow, uniform protein release rates. An interpretation of these results in terms of a qualitative model for the protein release mechanism is also given.     

Practice nurses and the care of patients receiving depot neuroleptic treatment: views on training, confidence and use of structured assessment

The movement of care into the community for the mentally ill with severe and enduring problems has important implications for primary care services. This paper reports the findings from an interview with practice nurses working in south-west London, United Kingdom, who had participated in a randomised control trial to investigate the effectiveness of training and structured assessment on clinical and social outcomes of patients receiving maintenance medication of depot antipsychotics. The aim of the interview was to explore current practice, attitudes, confidence and priorities for training in relation to these patients. Thirty-nine nurses were interviewed. The majority of practice nurses received scant referral information and worked without protocols. Even though these nurses had received the training, and as a result of the study had increased awareness of the problems of the severely mentally ill, there was a significant relationship between inadequate knowledge of schizophrenia to carry out the task of medication management and lack of confidence. Although the small size of the sample does not permit generalization, important questions are raised for further practice development and research, including the future training needs of practice nurses and partnership relationships with mental health professionals for supervision and support.     

Mechanism of adaptation of the vascular system to chronic changes in nitric oxide level in the organism

We studied the possibility of directed modulation of the efficiency of NO storage in rats due to adaptation to the chronic changes in plasma NO level. The efficiency of NO storage increased during long-term maintenance of high plasma level of NO and decreased in NO-deficient states. The compensatory changes in NO storage capacity of vessels depending on its organism content represent a new mechanism of adaptation of the cardiovascular system to chronic excess or deficit of NO, while directed modulation of this process can be important for the protection of the organism against both surplus or shortage of NO. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 12, pp. 626–630, December, 2006     

Leuprorelin acetate granulomas: case reports and review of the literature

Leuprorelin acetate, an agonist of gonadotropin-releasing hormone (GnRH), is indicated in the treatment of prostate cancer. Recently, depot formulations of leuprorelin acetate have been widely used. We report three patients who showed a granulomatous reaction after treatment using a leuprorelin acetate 3-month depot formulation. These patients presented with 5-6-cm subcutaneous nodules at injection sites, which developed after the depot type was changed from a 1-month to a 3-month formulation. Skin biopsy showed epithelioid cells and foreign body giant cells containing round, translucent microspheres which formed sarcoidal granulomas. Changing to other GnRH agonists resulted in no further problems. We have reviewed the previous reports of leuprorelin acetate-induced granuloma formation. The formation of such granulomas may be related to the polymers that allow slow release after injection, or leuprorelin acetate itself may be responsible. The depot injection methods using leuprorelin also seem to have a causal effect in granuloma formation. Dermatologists need to know that depot leuprorelin acetate may cause a granulomatous reaction which produces a subcutaneous nodule that might be misdiagnosed as a malignant tumour.