Treatment variables in relation to oocyte maturation: Lessons from a clinical micromanipulation-assisted in vitro fertilization program

Objective: In an effort to understand the mechanism underlying the improved pregnancy rate observed in IVF cycles when gonadotropin-releasing hormone analogues (GnRH-a) are applied, we investigated a possible relationship between treatment variables and oocyte-nuclear maturity. Design: Nuclear maturity was retrospectively assessed in cumulus-free, denuded oocytes, obtained from women undergoing micromanipulation-assisted IVF treatment following controlled ovarian hyperstimulation with GnRH-a and menotropins. Setting: The setting was the infertility and IVF unit of a tertiary academic medical center. Participants: Two hundred twenty-one patients underwent 435 treatment cycles. Main Outcome Measure: This was the proportion of germinal vesicle-intact immature (GVII) oocytes. Results: One hundred fifty-four of the 3520 oocytes studied (4.4%) were in the GVII stage. These oocytes were found in 66 of the treatment cycles (15.2%) and in 54 of the patients (24.4%). Cycles in which GVII oocytes were detected did not differ from those in which all the aspirated oocytes were mature in the following respects: patient age, type and duration of infertility, controlled ovarian hyperstimulation protocol and time of ovum pickup. However, the GVII group was characterized by a significantly higher peak estradiol level, as well as a higher number of mature follicles visualized sonographically (diameter, >14 mm) and oocytes retrieved. Conclusions: Comparing the present findings with previously published data, it appears that the inclusion of GnRH-a in the stimulation regimen is associated with a lower proportion of immature oocytes. A higher occurrence of oocyte-nuclear immaturity is apparently associated with a significantly better ovarian response to stimulation. The high incidence of immature oocytes observed in patients with normospermic partners and low fertilization rates in previous cycles may suggest that the fertilization failure in some of these cases is due to oocyte, rather than sperm, dysfunction.     

Radiation therapy induced changes in apoptosis and its major regulatory proteins, Bcl-2, Bcl-XL, and Bax, in locally advanced invasive squamous cell carcinoma of the cervix.

BACKGROUND AND PURPOSE: Radiation therapy (RT) for cancer induces cell death by apoptosis. The major apoptotic regulatory molecules include Bcl-2, Bcl-XL (antiapoptotic), and Bax (proapoptotic) proteins. Invasive squamous cell carcinoma of the cervix is mainly treated by radiation, and hence our aim was to evaluate the changes induced by RT in the apoptotic index (AI) and to correlate this to the levels of the major pro- and antiapoptotic molecules. MATERIALS AND METHODS: Paired biopsies were obtained in 30 cases of invasive carcinoma cervix before and after 10 Gy RT. The TUNEL assay was performed to detect apoptotic nuclei and Bcl-2, Bcl-XL, and Bax proteins detected by immunohistochemistry (IHC). Statistical analysis was performed using the Spearman rank correlation coefficient test. RESULTS: Following RT, there was a significant increase in the mean AI [2.25 (+/-2.28) in post-RT vs 0.90 (+/-0.53) in the pre-RT group]. Bax, a major proapoptotic protein, was significantly increased following RT (P < 0.05), whereas the antiapoptotic Bcl-XL showed a significant decrease (P = 0.006). There was no significant change in Bcl-2 expression. The Bcl-2 and Bax IHC scores and the Bcl-2/Bax ratio did not correlate with AI in the 2 groups. There was an inverse correlation of Bcl-XL to AI in the pre-RT group (P = 0.003) but not in the post-RT group. CONCLUSIONS: RT for invasive squamous cell carcinoma of cervix results in increased apoptotic cell death with the up-regulation of Bax, a proapoptotic protein, and the down-regulation of Bcl-XL, an antiapoptotic protein, without any significant change in the levels of Bcl-2.     

Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial.

PURPOSE: Biliary cancer has a poor prognosis, and chemotherapy has had little impact. The objectives of this trial were to determine the response rate, time to disease progression, survival, and safety profile of the combination of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer. PATIENTS AND METHODS: Eligible patients had pathologically proven, locally advanced or metastatic adenocarcinoma arising from the intra- and extrahepatic bile ducts or gallbladder with no prior chemotherapy. Patients were treated on a 3-week cycle consisting of capecitabine at 650 mg/m(2) orally twice a day for 14 days and gemcitabine at a fixed dose of 1,000 mg/m(2) intravenously over 30 minutes on days 1 and 8. RESULTS: Forty-five patients were enrolled between July 2001 and January 2004. Fifty-three percent of patients had cholangiocarcinoma, 47% had gallbladder cancer, and 89% had metastatic disease. The overall objective response rate was 31%, with an additional 42% of patients with stable disease, for a disease control rate of 73%. The median overall survival time was 14 months (95% CI, 7.3 months to not available), and the median progression-free survival time was 7 months (95% CI, 4.6 to 11.8 months). This chemotherapy combination was generally well tolerated. Transient neutropenia, thrombocytopenia, fatigue, and hand-foot syndrome were commonly observed but were easily managed without discontinuing further treatment. CONCLUSION: The significant antitumor activity combined with a mild toxicity profile seen in this study argue that GemCap chemotherapy may benefit patients with advanced biliary cancer. This regimen warrants further evaluation in a randomized study with survival and quality of life end points.     

Congenital Hyperinsulinemic Hypoglycemia and Hyperammonemia due to Pathogenic Variants in GLUD1

Indian Journal of Pediatrics - Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disorder, characterized by dysregulated insulin secretion. Pathogenic variants in at...     

Tribological Performance of High-Entropy Coatings (HECs): A Review

Surface coatings that operate effectively at elevated temperatures provide compatibility with critical service conditions as well as improved tribological performance of the components. High-entropy coatings (HECs), including metallic, ceramics, and composites, have gained attention all over the world and developed rapidly over the past 18 years, due to their excellent mechanical and tribological properties. High-entropy alloys (HEAs) are defined as alloys containing five or more principal elements in equal or close to equal atomic percentage. Owing to the high configurational entropy compared to conventional alloys, HEAs are usually composed of a simple solid solution phase, such as the BCC and FCC phases, instead of complex, brittle intermetallic phases. Several researchers have investigated the mechanical, oxidation, corrosion and wear properties of high-entropy oxides, carbides, borides, and silicates using various coating and testing techniques. More recently, the friction and wear characteristics of high-entropy coatings (HECs) have gained interest within various industrial sectors, mainly due to their favourable mechanical and tribological properties at high temperatures. In this review article, the authors identified the research studies and developments in high-entropy coatings (HECs) fabricated on various substrate materials using different synthesis methods. In addition, the current understanding of the HECs characteristics is critically reviewed, including the fabrication routes of targets/feedstock, synthesis methods utilized in various research studies, microstructural and tribological behaviour from room temperature to high temperatures.