This carries the multiplying new generations of V. cholerae bacteria out into the drinking water of the next host if proper sanitation measures are not in place.The cholera toxin (CTX or CT) is an oligomeric complex made up of six protein subunits: a single copy of the A subunit (part A), and five copies of the B subunit (part B), connected by a disulfide bond. The five B subunits form a five-membered ring that binds to GM1 gangliosides on the surface of the intestinal epithelium cells. The A1 portion of the A subunit is an enzyme that ADP-ribosylates G proteins, while the A2 chain fits into the central pore of the B subunit ring. Upon binding, the complex is taken into the cell via receptor-mediated endocytosis. Once inside the cell, the disulfide bond is reduced, and the A1 subunit is freed to bind with a human partner protein called ADP-ribosylation factor 6 (Arf6). Binding exposes its active site, allowing it to permanently ribosylate the Gs alpha subunit of the heterotrimeric G protein. This results in constitutive cAMP production, which in turn leads to the secretion of water, sodium, potassium, and bicarbonate into the lumen of the small intestine and rapid dehydration. The gene encoding the cholera toxin was introduced into V. cholerae by horizontal gene transfer. Virulent strains of V. cholerae carry a variant of a temperate bacteriophage called CTXφ.
The thyroid in pregnancy
Fetal thyroxine is wholly obtained from maternal sources in early pregnancy since the fetal thyroid gland only becomes functional in the second trimester of gestation. As thyroxine is essential for fetal neurodevelopment it is critical that maternal delivery of thyroxine to the fetus is ensured early in gestation. In pregnancy, iodide losses through the urine and the feto-placental unit contribute to a state of relative iodine deficiency. Thus, pregnant women require additional iodine intake. A daily iodine intake of 250 µg is recommended in pregnancy but this is not always achieved even in iodine sufficient parts of the world.Thyroid hormone concentrations in blood are increased in pregnancy, partly due to the high levels of estrogen and due to the weak thyroid stimulating effects of human chorionic gonadotropin (hCG) that acts like TSH. Thyroxine (T4) levels rise from about 6–12 weeks, and peak by mid-gestation; reverse changes are seen with TSH. Gestation specific reference ranges for thyroid function tests are not widely in use although many centres are now preparing them. Hypothyroidism
Clinical evaluation
Hypothyroidism is common in pregnancy with an estimated prevalence of 2-3% and 0.3-0.5% for subclinical and overt hypothyroidism respectively. Endemic iodine deficiency accounts for most hypothyroidism in pregnant women worldwide while chronic autoimmune thyroiditis is the most common cause of hypothyroidism in iodine sufficient parts of the world. The presentation of hypothyroidism in pregnancy is not always classical and may sometimes be difficult to distinguish from the symptoms of normal pregnancy.