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Biomedical subjects

F Q Zhou

Publications and source records attributed to F Q Zhou.

At least 19 recordsLinked to original sources

Growth cone collapse through coincident loss of actin bundles and leading edge actin without actin depolymerization.

Repulsive guidance cues can either collapse the whole growth cone to arrest neurite outgrowth or cause asymmetric collapse leading to growth cone turning. How signals from repulsive cues are translated by growth cones into this morphological change through rearranging the cytoskeleton is unclear. We examined three factors that are able to induce the collapse of extending Helisoma growth cones in conditioned medium, including serotonin, myosin light chain kinase inhibitor, and phorbol ester. To study the cytoskeletal events contributing to collapse, we cultured Helisoma growth cones on polylysine in which lamellipodial collapse was prevented by substrate adhesion. We found that all three factors that induced collapse of extending growth cones also caused actin bundle loss in polylysine-attached growth cones without loss of actin meshwork. In addition, actin bundle loss correlated with specific filamentous actin redistribution away from the leading edge that is characteristic of repulsive factors. Finally, we provide direct evidence using time-lapse studies of extending growth cones that actin bundle loss paralleled collapse. Taken together, these results suggest that actin bundles could be a common cytoskeletal target of various collapsing factors, which may use different signaling pathways that converge to induce growth cone collapse.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Advantages of pyruvate over lactate in peritoneal dialysis solutions.

This review discusses effects of both lactate and pyruvate, and high glucose in peritoneal dialysis solutions (PDS) on leukocytes, mainly on intracellular pH ([pH](i)), glucose metabolic pathways, and apoptosis. Lactate-based PDS (L-PDS) are bioincompatible primarily due to the low pH, high lactate, and glucose excess in both individual and combination. High lactate in an acidi milieu would induce severe intracellular acidosis of leukocytes, and high glucose may disturb glucose metabolic pathways and activate protein kinase C (PKC) and nuclear factor-kappa B (NF-kappaB) of the cells, leading to apoptosis. Pyruvate-based PDS (P-PDS) are novel experimental PDS. Evidence shows that P-PDS are superior in biocompatibility. Pyruvate protection of cells has been confirmed in many fields besides the PDS area. Although the underlying mechanism whereby P-PDS preserve cell function is not fully understood, it may be associated with the maintenance of [pH](i) close to physiological, due to its low buffering capacity, improvement of cellular glucose metabolic pathways and redox state, and sustainment of intracellular calcium ([Ca2+]i) homeostasis in high glucose concentrations. It may also inhibit PKC and NF-kappaB activation in high glucose. In addition, pyruvate is a strong antioxidant, a scavenger of hydrogen peroxide (H2O2). However, exogenous pyruvate in PDS could not be an energy source for cells and also the Crabtree effect might not occur in neutrophils. Pyruvate is a hopeful candidate of buffers in PDS in the near future. Further observation of P-PDS is strongly needed with peritoneal cells to verify the cell protection both in vitro and in vivo before clinic trials.

Apoptosis↗

Neutrophilic transient acidification and superoxide production in peritoneal dialysate.

AIM: To elucidate whether an inhibited superoxide production (O2-) of neutrophils induced by commercial lactate-based peritoneal dialysates (PDS) could be corrected after a transient intracellular acidosis. METHODS: The intracellular pH ([pHi]) of human neutrophils incubated in PDS was monitored with a spectrofluorometer with a pH-sensitive dye (BCECF-AM). Neutrophilic O2- stimulated by zymosan was determined in PDS with the superoxide dismutase inhibitable ferricytochrome c reduction, using a spectrophotometer. RESULTS: The severe intracellular acidosis induced within 5 min by PDS at an extracellular pH of 5.2 could be promptly and completely recovered by a neutralization of the pH of media. However, O2- by neutrophils exposed to the PDS for as little as 5 min was drastically and persistently inhibited, even the acidic [pHi] of cells had been fully returned for 1 h. CONCLUSIONS: The intracellular acidification of cells in the initial phase could be transient and reversible, but impaired cell functions, at least in part including O2- generating system, might be consistent and irreversible in the early stage of the cellular acidosis in the peritoneal cavity of CAPD patients. The findings above may be of particular importance in both clinic and cell biology.

Acidosis↗

Pyruvate-based peritoneal dialysate preserves neutrophilic oxygen consumption.

AIM: To investigate effects of pyruvate- or lactate-based peritoneal dialysis solutions (P-PDS or L-PDS) on neutrophilic oxygen consumption and the role of the extracellular pH (pHe) in cells' oxygen uptake. METHODS: Human neutrophils were incubated in P-PDS or L-PDS containing pyruvate or lactate 35-38 mmol.L-1 at various pHe, respectively. Oxygen consumption rates by opsonized zymosan (OZ)-stimulated cells were measured polarographically, using a Clark-type oxygen electrode. RESULTS: L-PDS at an initial pH 5.2 dramatically inhibited the rate of oxygen consumption (2.2 nmol.min-1/10(6) cells) by neutrophils, while the equally acidic P-PDS markedly improved the rate (6.4 nmol.min-1/10(6) cells) (P < 0.01). However, P-PDS at pHe 5.2 severely impaired the rate by cells, the same as pHe 5.2 L-PDS. CONCLUSION: P-PDS preserved an oxygen consumption rate by OZ-stimulated human neutrophils, but in an acidi milieu it comparably deteriorated the ability of cells to consume oxygen, indicating that the pHe of PDS plays an essential role in cellular oxidative metabolism. The superior biocompatibility of an acidic P-PDS was associated with its lower buffering capacity.

Dialysis Solutions↗

[Glutamate causes release of nitric oxide from chicken spinal cord in vitro].

Nitric oxide (NO) has been identified to have profound effects on many systems, especially the neural tissues. Many studies suggest that NO mediate the neurotoxicity of glutamate (Glu). In order to determine in vitro whether Glu causes release of NO from chicken spinal cord, different concentrations of Glu (0.1, 0.5, 1.0 mmol.L-1) were added to the primary cultured chicken spinal cord cells, and the quantity of NO- (the metabolism product of NO) in medium was detected. The result shows that Glu can enhance obviously the concentration of NO in primary cell cultures (212% compared with the control). If the spinal cord cells were pretreated with NO synthases (NOS) inhibitor--L-NOARG, the [NO-] was decreased compared with those treated with Glu only, and, on the contrary, the viability of cells was increased. All of the results above indicate that NO may play an important role in the neurotoxicity of Glu on nervous cells. It might be that Glu can instigate the activity of NO synthases, then induce a series of changes within cell and finally lead to the toxic effect on cells.

Animals↗

Effects of pyruvate-based or lactate-based peritoneal dialysis solutions on neutrophil intracellular pH.

Acidic (pH 5.2) incubation mixtures containing pyruvate-based or lactate-based peritoneal dialysis solutions (PDSN's) induced comparable degrees of intracellular acidosis in neutrophils. However, addition of an acidic (pH 5.2), pyruvate-based PDSN to a pH-7.4, neutrophil/phosphate-buffered saline mixture brought about higher extracellular and intracellular (neutrophil) pH values when compared to the introduction of an equally acidic, lactate-based PDSN. This poor ability of acidic (pH 5.0-5.5), pyruvate-based PDSN's to resist alkalinizing influences is the cause for the above higher pH values. The higher intracellular pH levels so obtained may be a reason behind why acidic, pyruvate-based PDSN's appear to be more biocompatible than their equally acidic, lactate-based counterparts.

Adult↗

Effects of a pH 7.4, lactate-based and a pH 7.4, bicarbonate-based peritoneal dialysis solutions on neutrophil superoxide generation.

Neutrophil superoxide formation was similar when cells were incubated in self-made, non-autoclaved pH 7.4, lactate-based peritoneal dialysis solutions or in their self-made, non-autoclaved, pH 7.4, bicarbonate-based counterparts. On the other hand, commercially available, autoclaved, pH 7.4, lactate-based peritoneal dialysis solutions resulted in inhibition of superoxide production when compared to their self-made, non-autoclaved, pH 7.4, lactate-based or bicarbonate-based counterparts. The cause for this inhibition of superoxide generation is at present unknown.

Adult↗

Collection of a representative fraction of total spent hemodialysate.

We describe a method of obtaining a small representative fraction of spent dialysate by placing a side tube in the dialysate drainage tube. The side tube, capped with a small-gauge needle, is used to collect the specimen. Fractions obtained in this fashion are found to have a composition similar to that of the remaining spent dialysate.

Hemodialysis Solutions↗

Neutrophil intracellular pH after exposure of neutrophils to a euhydric, lactate-based peritoneal dialysis solution and its euhydric, bicarbonate-based counterpart.

The effects of euhydric, lactate-based peritoneal dialysis solutions and those of their euhydric, bicarbonate-based counterparts, on neutrophil intracellular pH are comparable. This similarity in effects on intracellular acidity may have bearings on the influences of these solutions on cellular functions in general.

Adolescent↗

Effects of an acidic, lactate-based peritoneal dialysis solution and its euhydric, bicarbonate-based counterpart on neutrophilic intracellular pH.

An exposure of human neutrophils to an acidic (pH 5.2), lactate-based incubation mixture containing a conventional, acidic, lactate-based peritoneal dialysis solution (PDS) resulted in the development of a prompt and substantial intracellular acidosis. A comparable exposure to a euhydric, bicarbonate-based incubation mixture containing a euhydric, bicarbonate-based PDS did not bring about similar changes in intracellular pH. The absence of an intracellular acidosis in the instance of the euhydric, bicarbonate-based PDS may be the reason why this solution is more biocompatible than its acidic, lactate-based counterpart.

Bicarbonates↗