Fluids Hypertension Syndromes: Migraines, Headaches, Normal ...

Fluids Hypertension Syndromes – Dr. Leonardo Izecksohn – page 289
XVII- 32 - Chemotherapy and radiotherapy enhancement: “Pemetrexed is a new generation antifolate
approved for the treatment of mesothelioma and non-small cell lung cancer. Caffeine is known
to augment radiation or chemotherapeutic drug-induced cell killing. Caffeine sensitization occurred
only in cells subjected to pulse, but not continuous, exposure to pemetrexed. Similar pemetrexed sensitization
was also observed with the clinically better tolerated caffeine analog, theobromine. These data
indicate that caffeine and its analog, theobromine, may be a useful approach to enhance pemetrexed-based
chemotherapy.” (Min S H, and others).
“These results demonstrate that enhancement of cytotoxic activity against cis-diamminedichloroplatinum-treated
cells by caffeine is characterized by an acceleration of DNA degradation in G2 + M phase,
namely apoptotic cell death.” (Shinomiya N, and others).
“Cellular modulation of the cell cycle with pentoxifylline and caffeine radiosensitized LS180 colon
cancer cells exposed to 186Re radiation.” (Kinuya S, and others).
“1-methylxanthine significantly increased the radiosensitivity of RKO human colorectal cancer cells
carrying wild type p53 mainly by inhibiting the repair of radiation-induced DNA DSB without causing
significant alteration in radiation-induced G2/M arrest.” (Youn H, and others).
XVII- 33 -Cell death enhancement caused by hyperoxia: “Reactive oxygen species produced during
hyperoxia damage DNA, inhibit proliferation in G1- through p53-dependent activation of
p21(Cip1/WAF1/Sdi1), and kill cells... Addition of caffeine, which inactivates the G2 checkpoint, diminished
the percentage of hyperoxic cells in G2 and increased the percentage in sub-G1 and G1. Abrogation
of the G2 checkpoint was associated with enhanced oxygen-induced DNA strand breaks and
cell death. Caffeine did not affect DNA integrity or viability of cells exposed to room air.” (O'Reilly M
A, and others).
XVII- 34 -Erectile function improvement on diabetic rats: “The intracavernous pressure and the
cavernous cyclic guanosine monophosphate decreased significantly in the diabetic rats compared to the
normal controls. An 8-week administration of caffeine at the given dosages increased the intracavernous
pressure and cavernous cyclic guanosine monophosphate in diabetic rats. In conclusion, caffeine
consumption improved the erectile function of diabetic rats by up-regulating cavernous cyclic
guanosine monophosphate.” (Yang R, and others).
XVII- 35 - Fibroblast antiproliferative effect: “We conclude that xanthine derivatives are good candidates
for use as fibroblast antiproliferative drugs. Caffeine was the most active compound followed
by theophylline and dyphylline.” (Levi-Schaffer F, and Touitou E.)
XVII- 36 -Headaches post-lumbar puncture reduction: (Post-spinal tap headache caused by
Cerebrospinal Fluid’s dural leakage and its hypo-tension): “The use of intravenous caffeine benzoate
(500 mg infusion over 1 h) also has been found to treat post-lumbar puncture headaches effectively in
double-blind, controlled trials.” (Sucholeiki R, and Waldman A L).
XVII- 37 - PARP-1 enzyme inhibition: “The major caffeine metabolite 1,7-dimethylxanthine has
significant PARP-1 (poly(ADP-ribose)polymerase-1 (E.C.2.4.2.30)) inhibiting activity in cultured epithelial
and endothelial cells at physiological concentrations. This inhibition could have important implications
for nutritional treatment of acute and chronic inflammatory pathologies, like prevention of
ischemia-reperfusion injury or vascular complications in diabetes.” (Geraets L, and others).