Prevention of Milk Fever by Dietary Means

A concentrate was fortified with mineral salts by adding CaCl2, Al2(SO4)3 and MgSO4 to standard concentrate A and pelleting the product When used as feed supplement from 3 weeks pre partum to 1 week post partum this concentrate mixture produced the intended negative alkali alkalinity in the total feed ration in 20 out of 25 cows. Of these 17 remained healthy in spite of a history of milk fever for the majority of them. Two cows got milk fever and 1 showed weak symptoms.     

Plasma Constituents in the Sow

The concentrations in plasma of total protein, urea-N, Ca, Mg, Na and K and the activity of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in plasma were studied in 20 sows from one week before weaning until four weeks after weaning. Ten of the sows resumed ovarian activity within 10 days after weaning, while in the other 10 sows the resumption of ovarian activity was delayed. Plasma glucose was studied in 10 sows from one week before weaning until two weeks after weaning, five of these sows had delayed resumption of ovarian function. After weaning the concentration of total protein and the ALAT activity increased, while plasma glucose and Mg decreased. Concerning ASAT, Ca, Na and K no changes were observed. A transient increase in urea-N level took place after weaning in sows with prolonged weaning-to-ovulation period. In sows with normal weaning-to-ovulation period no change in urea-N was observed. This was the only difference in blood chemistry observed between sows with normal weaning-to-ovulation period and sows with prolonged weaning-to-ovulation period.     

Differential Effects of 670 and 830 nm Red near Infrared Irradiation Therapy: A Comparative Study of Optic Nerve Injury,Retinal Degeneration,Traumatic Brain and Spinal Cord Injury

Red/near-infrared irradiation therapy (R/NIR-IT) delivered by laser or light-emitting diode (LED) has improved functional outcomes in a range of CNS injuries. However, translation of R/NIR-IT to the clinic for treatment of neurotrauma has been hampered by lack of comparative information regarding the degree of penetration of the delivered irradiation to the injury site and the optimal treatment parameters for different CNS injuries. We compared the treatment efficacy of R/NIR-IT at 670 nm and 830 nm, provided by narrow-band LED arrays adjusted to produce equal irradiance, in four in vivo rat models of CNS injury: partial optic nerve transection, light-induced retinal degeneration, traumatic brain injury (TBI) and spinal cord injury (SCI). The number of photons of 670 nm or 830 nm light reaching the SCI injury site was 6.6% and 11.3% of emitted light respectively. Treatment of rats with 670 nm R/NIR-IT following partial optic nerve transection significantly increased the number of visual responses at 7 days after injury (P≤0.05); 830 nm R/NIR-IT was partially effective. 670 nm R/NIR-IT also significantly reduced reactive species and both 670 nm and 830 nm R/NIR-IT reduced hydroxynonenal immunoreactivity (P≤0.05) in this model. Pre-treatment of light-induced retinal degeneration with 670 nm R/NIR-IT significantly reduced the number of Tunel+ cells and 8-hydroxyguanosine immunoreactivity (P≤0.05); outcomes in 830 nm R/NIR-IT treated animals were not significantly different to controls. Treatment of fluid-percussion TBI with 670 nm or 830 nm R/NIR-IT did not result in improvements in motor or sensory function or lesion size at 7 days (P>0.05). Similarly, treatment of contusive SCI with 670 nm or 830 nm R/NIR-IT did not result in significant improvements in functional recovery or reduced cyst size at 28 days (P>0.05). Outcomes from this comparative study indicate that it will be necessary to optimise delivery devices, wavelength, intensity and duration of R/NIR-IT individually for different CNS injury types.     

Neutral 5-substituted 4-anilinoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase

Neutral 5-substituted 4-anilinoquinazolines addressed high in vivo clearance and phospholipidosis associated with previous basic compounds. A representative compound 8a inhibited tumor growth in a mouse xenograft model when co-administered with the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT), and data are consistent with pharmacology primarily reflecting inhibition of erbB2 receptor tyrosine kinase.     

Prevention of Milk Fever (Hypocalcemic Paresis Puerperalis) by Dietary Salt Supplements

Twelve cows of 14 given a basic diet supplemented with Na2GO3 and NaHCO3 during four weeks pre partum and one week past partum were attacked by milk fever (hypocalcemic paresis puerperalis), while 12 cows of 13 receiving the same basic diet supplemented with sulfates and chlorides remained healthy. A mixture of CaCl2, Al2(SO4)3 and MgSO4 was found to be a convenient prophyllactic supplement. It was found possible to induce and prevent milk fever at successive parturitions in the same cow by altering the dietary conditions. The data give further support to the hypothesis that the alkali alkalinity of the diet is the major factor in induction or prevention of milk fever.     

Sulfonyl-morpholino-pyrimidines: SAR and development of a novel class of selective mTOR kinase inhibitor

High throughput screening to identify inhibitors of the mTOR kinase revealed sulfonyl-morpholino-pyrimidine 1 as an attractive start point. The compound displayed good physicochemical properties and selectivity over related kinases such as PI3Kα. Library preparation of related analogs allowed the establishment of additional SAR understanding and in particular the requirement for a key hydrogen bond donor motif at the 4-position of the phenyl ring in compounds such as indole 19. Isosteric replacement of the indole functionality led to the identification of urea compounds such as 32 that show good levels of mTOR inhibition in both enzyme and cellular assays.