MOG analogues to explore the MCT2 pharmacophore, α-ketoglutarate biology and cellular effects of N-oxalylglycine.

α-ketoglutarate (αKG) is a central metabolic node with a broad influence on cellular physiology. The αKG analogue N-oxalylglycine (NOG) and its membrane-permeable pro-drug derivative dimethyl-oxalylglycine (DMOG) have been extensively used as tools to study prolyl hydroxylases (PHDs) and other αKG-dependent processes. In cell culture media, DMOG is rapidly converted to MOG, which enters cells through monocarboxylate transporter MCT2, leading to intracellular NOG concentrations that are sufficiently high to inhibit glutaminolysis enzymes and cause cytotoxicity.

Investigation of Janus Kinase (JAK) Inhibitors for Lung Delivery and the Importance of Aldehyde Oxidase Metabolism.

The Janus family of tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) play an essential role in the receptor signaling of cytokines that have been implicated in the pathogenesis of severe asthma, and there is emerging interest in the development of small-molecule-inhaled JAK inhibitors as treatments. Here, we describe the optimization of a quinazoline series of JAK inhibitors and the results of mouse lung pharmacokinetic (PK) studies where only low concentrations of parent compound were observed. Subsequent investigations revealed that the low exposure was due to metabolism by aldehyde oxidase (AO), so we sought to identify quinazolines that were not metabolized by AO.

Serial estimation of Th1:th2 cytokines profile in women undergoing in-vitro fertilization-embryo transfer.

Problem: To investigate changes in the ratio of T-cell subpopulations expressing intracellular T helper1 (Th1) and T helper 2 (Th2) cytokines in women with a history of recurrent failed implantation under going in-vitro fertilization (IVF)-embryo transfer.

Method Of Study: Twenty-eight peripheral blood samples were obtained at two time points, from 14 women undergoing IVF treatment; eight women with a history of recurrent failed implantation, who did not get pregnant in the index IVF cycle and six who had one or more previous successful IVF pregnancy and who became pregnant in the index IVF cycle. The proportion of lymphocytes expressing interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), and interleukin 4 (IL-4) and the Th1:Th2 ratios of IFN-gamma:IL-4, and TNF-alpha:IL-4 in T helper cells was measured by flow cytometry, in samples obtained before commencing IVF treatment and in samples obtained after ovarian stimulation (on the day of oocyte retrieval).

Cytokine profiles in serum and peritoneal fluid from infertile women with and without endometriosis.

Objective: To study the serum and peritoneal fluid cytokine profiles in infertile women with minimal/mild active endometriosis.

Methods: Fifty-seven consecutive infertile women undergoing laparoscopy for unexplained infertility had peritoneal fluid and serum samples obtained at the time of laparoscopy. The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotatic protein-1 (MCP-1), RANTES, platelet derived growth factor (PDGF), soluble Fas (sFas), and soluble Fas Ligand (sFasL) in peritoneal fluid and serum were measured to compare the concentration in both biological fluids, in women who have minimal/mild red endometriosis using women with no endometriosis as controls.

Initial investigation of the infertile couple. Pre-clinic request of investigations to facilitate diagnosis: utilising the waiting time to minimise delay.

Objective: To evaluate the effectiveness of pre-clinic request of investigations to facilitate diagnosis in couples referred to the infertility clinic and to assess patient satisfaction of the concept.

Study Design: Prospective cohort study with analysis of patient satisfaction questionnaire. Investigation packs were sent to patients in advance of their clinic appointment.

Best practice in primary care pathology: review 4.

This fourth best practice review examines four series of common primary care questions in laboratory medicine are examined in this review: (1) safety monitoring for three common drugs; (2) use of prostate-specific antigen; (3) investigation of vaginal discharge; and (4) investigation of subfertility. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of the guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents.

Gestational intestinal obstruction: a case report and review of literature.

Intestinal obstruction in pregnancy is rare and difficult to diagnose. Common causes of gestational intestinal obstruction include adhesions, volvulus, intussuscetion, carcinoma, hernia and appendicitis [3]. Abdominal pain is a common feature, but the displacement of abdominal organs as pregnancy progresses results in atypical location of the pain and hence delay in diagnosis.

Follicle tracking of women receiving clomiphene citrate for ovulation induction.

Forty-five cycles of forty subfertile women were monitored with follicle tracking. Thirty women were anovulatory and 10 had unexplained infertility. Thirty women responded to the initial dose of Clomiphene Citrate (CC) and 10 remained anovulatory.

ACP best practice no 170. Investigation of infertility with the emphasis on laboratory testing and with reference to radiological imaging.

This review will discuss the investigation of infertility, with emphasis on laboratory testing and reference to the value of other investigations, including clinical and radiological. The role of laboratory investigations is viewed within an appropriate clinically directed pathway that includes medical, surgical, and social history together with environmental factors. Because embryology and assisted reproduction techniques are developing rapidly and produce continuous changes in everyday practice, this article gives a critical review of the plethora of tests that are currently used.

The duration of lochia.

The duration of lochia and its association with a number of obstetric variables was studied in 236 women. Each woman completed a diary sheet describing the colour and duration of her lochia for up to 60 days post partum. The phases of lochia were divided according to the classical description; lochia rubra, serosa and alba.

The demonstration of saphenofemoral incompetence; doppler ultrasound compared with standard clinical tests.

Patients with primary varicose veins were examined by a combination of the standard tourniquet test with detection of reflux by Doppler ultrasound. Results were compared with standard clinical tests: impulse or thrill at the saphenous opening on coughing, tap impulse at the groin, and the 'Trendelenburg' tourniquet test. The state of competence of the saphenofemoral junction was noted at operation.