Acupuncture improves chemotherapy-induced neuropathy explored by neurophysiological and clinical outcomes - The randomized, controlled, cross-over ACUCIN trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is recognized as the second commonest side effect after chemotherapy. Besides neurological deficits and pain, it is a potential reason for terminating chemotherapy. Effective curative treatments of neurodegeneration are lacking. Hitherto, no randomized controlled study used nerve conduction studies (NCS), the gold standard diagnostic tool for peripheral neuropathy, as the primary outcome parameter for evaluating acupuncture for CIPN, which can also measure structural changes. METHODS: The study was carried out at the HanseMerkur Center for TCM at the University Medical Center, Hamburg-Eppendorf. Sixty patients with CIPN were included in the study after physical examination, subjective evaluation and quantitative evaluation by NCS. Subsequently, the patients were randomly assigned to Group 1 (30 patients), which received, in the first period, needle acupuncture and to Group 2 (30 patients), which was assigned to the waiting list in the first period. Group 1 received a standard 10-week bilateral treatment of ST34 (Liangqiu), EX-LE12 (Qiduan) and EX-LE8 (Bafeng). After 14 weeks, both groups were re-evaluated. Using a cross-over design, the patients of Group 2 received the same treatment procedure as Group 1 in the first period. Patients of Group 1 were assigned to the waiting list for the second period. After 28 weeks both groups were re-evaluated. Wilcoxon test was used as a pre-test to rule out carryover effects and to test for differences between acupuncture and the waiting list. Group assignment was not exposed to the statistician and the neurologist. RESULTS: Sural sensory nerve amplitude, and sural nerve conduction velocity, were significantly improved (p < 0.01, effect size (f) 0.55 and 0.49) compared to measurements in the waiting period. Change of NCS of the tibial nerve did not significantly differ in group comparison. Patients reported subjective improvement during acupuncture treatment superior to the waiting period for burning pain, cramps, numbness, frequency of symptoms (all p < 0.01) and unsteadiness of gait (p < 0.05). On physical examination, blind walking, heel-to-toe walking, distal pallhypesthesia (both p < 0.01), and the neuropathy deficit score (p < 0.05) were significantly improved during acupuncture treatment compared to the waiting period. CONCLUSION: Acupuncture can enhance structural regeneration in CIPN as measured by NCS, which is manifested in subjective improvement and neurological findings.

Puerariae lobatae root extracts and the regulation of brown fat activity.

BACKGROUND: Obesity is one of the major health problems worldwide. The induction of brown adipocyte formation and activity represents a promising therapeutic option by increasing energy expenditure. Asian herbs have the potential to treat obesity, however, pharmacological effects should be well documented at the molecular level first. HYPOTHESIS: A novel hypothesis-driven screening approach identified the root of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (PLR) to have potential effects on obesity by stimulating brown adipocytes. STUDY DESIGN: This study explored the metabolic effects of PLR water extract (PLRE) in a high-fat diet-induced obesity mouse model and characterized its secondary metabolite composition. METHODS: Animals were orally treated daily for two weeks and the bioactivity of PLRE evaluated by measuring various parameters including body weight, circulating metabolites, energy expenditure and insulin sensitivity. The chemical composition of the mains components was obtained by HPLC-MS-ELSD-PDA. Based on the dereplication results and semi-quantitative estimation, pure molecules were selected for tests on adipocytes in vitro. RESULTS: PLRE induces brown adipocyte activity and triggers the formation of brown-like cells in inguinal fat tissue, weight loss, and improved glucose metabolism. These effects are primarily caused by cell-autonomous activation of brown adipocytes and not by autonomic nervous system regulation. Even though the analysis of PLRE revealed puerarin as the most abundant secondary metabolite, it showed no effect on brown adipocyte formation and function. Brown adipocyte activity was induced dose-dependently by two other isoflavones, daidzein, and genistein. Daidzein is present in a very small amount in PLRE, but various glycosidic isoflavones, including puerarin, may release daidzein after metabolism. CONCLUSION: This approach demonstrated the positive effects of PLRE on a diet-induced obesity mouse model and provided clues on the mode of action of PLRE at the molecular level.

Salmonella typhimurium thyA mutants fail to grow intracellularly in vitro and are attenuated in mice.

Salmonella typhimurium ATCC14028 readily multiplies in professional phagocytes in vitro and is highly virulent in mice. Mutants lacking thymidylate synthase activity (thyA) were isolated and shown to be strictly dependent on thymidine monophosphate precursors in the growth medium. The thyA mutants were found to be virtually incapable of intracellular growth and survival in vitro, both in macrophage-like cell line P338D(1) and in the human epithelial cell line Hep-2, and their virulence was impaired in BALB/c mice. Intraperitoneal immunization of mice with two doses of live S. typhimurium thyA provided protection against a challenge with 10(3) times the 50% lethal dose of the virulent parent strain.