The effect of recombinant GM-CSF on the recovery of monkeys transplanted with autologous bone marrow

The regulatory function of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte production in vivo was evaluated in an autologous bone marrow transplantation model using rhesus monkeys. Monkeys were exposed to 9.0 Gy total body irradiation and then transplanted with 5.0 x 10(7) low-density bone marrow cells/kg. Alzet miniosmotic pumps were subcutaneously implanted to deliver rhGM-CSF at a rate of 50,400 U/kg/d. Minipumps, containing either rhGM-CSF or saline, were implanted between zero and five days after transplantation for seven days. Kinetic recoveries of peripheral blood cells after either saline or rhGM-CSF treatment were compared. Treatment with rhGM-CSF accelerated the recovery of neutrophils. Neutrophils in rhGM-CSF-treated animals recovered to 80% (3.4 x 10(3)/mm3) pre-irradiation control levels by day 20, in comparison with only 33% (0.9 x 10(3)/mm3) recovery for saline control monkeys. In addition, the recovery of neutrophils was enhanced over that of the controls, reaching 140% v 70% on day 30. Another prominent feature of rhGM-CSF-treated monkeys was the accelerated recovery of platelets, reaching near 50% normal levels by day 24 in comparison with 20% of normal levels for controls. The infusion of rhGM-CSF was shown to be an effective regulator of early hematopoietic regeneration, leading to the accelerated recovery of both neutrophils and platelets and then providing a consistent sustained increase of neutrophils even in the absence of rhGM-CSF.     

Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Michaelson MD,McKay RR,Werner L,Atkins MB,Van Allen EM,Olivier KM,Song J,Signoretti S,McDermott DF,Choueiri TK.Cancer. 2015 Oct 1;121(19):3435-43. [Epub 2015 Jun 8]. doi: 10.1002/cncr.29503.

Background

Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC.

Comparative evaluation of gustatory function between postmenopausal women and age‐matched men

Oral Diseases (2010) 16 , 469–475 Objective: The aim of the study was to compare the gustatory function between postmenopausal women and age‐matched men. Subjects and methods: During a period of 4 months, 30 postmenopausal women and 30 age‐matched men were prospectively evaluated for gustatory function. Each subject was given a symptoms questionnaire for self‐assessment of taste function. Then, whole mouth taste test was performed in which the quality identification and intensity ratings of taste solutions were measured. Results: Regarding correct quality identification, the results were statistically non‐significant (P > 0.05). As far as the intensity judgments are concerned, significant difference exists between postmenopausal women and age‐matched men. Intensity of taste perception for sucrose was significantly lower in postmenopausal women than intensity of taste perception for other tastes (P < 0.05). One of the noticeable findings is that 15 (50%) postmenopausal women reported a change in dietary habits; all expressed liking for sweeter food. Conclusion: Postmenopausal women appeared to have a reduced perception of sucrose, which can alter eating habits, such as intake of more sweet foods, whereas no significant difference is observed in taste perception of NaCl, citric acid and quinine hydrochloride between postmenopausal women and age‐matched men. Fifteen (50%) postmenopausal women stated fondness for sweet taste.     

Cannabidiol inhibits synaptic transmission in rat hippocampal cultures and slices via multiple receptor pathways

BACKGROUND AND PURPOSE

Cannabidiol (CBD) has emerged as an interesting compound with therapeutic potential in several CNS disorders. However, whether it can modulate synaptic activity in the CNS remains unclear. Here, we have investigated whether CBD modulates synaptic transmission in rat hippocampal cultures and acute slices.

EXPERIMENTAL APPROACH

The effect of CBD on synaptic transmission was examined in rat hippocampal cultures and acute slices using whole cell patch clamp and standard extracellular recordings respectively.

KEY RESULTS

Cannabidiol decreased synaptic activity in hippocampal cultures in a concentration-dependent and Pertussis toxin-sensitive manner. The effects of CBD in culture were significantly reduced in the presence of the cannabinoid receptor (CB₁) inverse agonist, {"type":"entrez-nucleotide","attrs":{"text":"LY320135","term_id":"1257555575","term_text":"LY320135"}}LY320135 but were unaffected by the 5-HT_1A receptor antagonist, WAY100135. In hippocampal slices, CBD inhibited basal synaptic transmission, an effect that was abolished by the proposed CB₁ receptor antagonist, AM251, in addition to {"type":"entrez-nucleotide","attrs":{"text":"LY320135","term_id":"1257555575","term_text":"LY320135"}}LY320135 and WAY100135.

CONCLUSIONS AND IMPLICATIONS

Cannabidiol reduces synaptic transmission in hippocampal in vitro preparations and we propose a role for both 5-HT_1A and CB₁ receptors in these CBD-mediated effects. These data offer some mechanistic insights into the effects of CBD and emphasize that further investigations into the actions of CBD in the CNS are required in order to elucidate the full therapeutic potential of CBD.     

Pin1 levels are downregulated during ER stress in human neuroblastoma cells

Previously, we showed that pretangle neurons in Alzheimer’s disease (AD) brain display unfolded protein stress in the endoplasmic reticulum (ER). Others showed that the peptidylprolyl isomerase Pin1 protects against tangle formation by facilitating tau dephosphorylation, corroborating with the lower expression of Pin1 observed in tangle-bearing neurons. In this study, we investigated Pin1 expression under ER stress conditions. We show that in human, but not mouse neuroblastoma cells, Pin1 is downregulated in response to ER stress, in accordance with the presence of an ER stress response element in the mouse, but not the human Pin1 gene. This study creates a starting point to investigate whether modulation of the ER stress response may prevent or delay tau pathology in AD.