The meddling microbes midst our medicines

It is not surprising that the complex metabolic machinery of the gut microbiome has accidental, or directed, ability to alter our medicines and influence their efficacy. What is not known is the extent to which this has contributed to drug failures or contraindications, or to the derailment of clinical trials. Some studies are unraveling the mechanisms by which the microbiota alter specific drugs, such as digoxin, and contribute to variations in efficacies between patient populations. Microbiome profiling, therefore, may well become an inevitable arm of all clinical trials in the future.     

Wenckebach periods with repetitive block: evaluation with His bundle recording

Two patients are reported in whom repetitive block of two consecutive P waves occurred during Wenckebach beating induced by atrial pacing. His bundle recordings revealed block proximal to H in the first case, suggesting inhomogeneous conduction in the A-V node. In the second case, long cycle lengths were produced in the His-Purkinje system due to A-V nodal Wenckebach periods. The long cycles prolonged refractory periods in the His Purkinje system so that subsequent beats (short cycles) were blocked distal to H.The repetitive block of consecutive multiple atrial impulses could result in unexpected degrees of ventricular asystole during usually benign Type I second-degree A-V block.     

Some observations on the role of LH receptor binding inhibitor of ovine corpora lutea in ovarian processes

Preliminary studies, both in vitro and in vivo were carried out to understand the physiological significance of LH receptor binding inhibitors isolated from ovine corpora lutea. Among the four active fractions tested, while UM-2R-III administered intraperitoneally suppressed both hMG and hCG-induced stimulation of uterine weights in immature mice, UM-2R-IX reduced the hCG-induced uterine weight. Fraction UM-2R-III inhibited both FSH and LH-stimulated cyclic AMP production by rat granulosa cells. Intraperitoneal injections of UM-2R-III and IX to adult cycling rats on the day of proestrus partially blocked ovulation. Similar i.p. treatment of cycling rats in 2 doses on day 1 of diestrus, prevented implantation/or early pregnancy (on 10th day of pregnancy) in 70 to 80% of rats. As the plasma levels of progesterone were low in the treated animals compared to the control, the decrease was attributed to the inadequate development of the corpus luteum. Of these fractions, UM-2R-IX was more effective at 5 to 10 times less doses compared to UM-2R-III. Further studies are needed to assess the route and dose of administering the active LHRBR components.