Cytokine networks in destructive periodontal disease

BACKGROUND Cytokines are important regulatory proteins, produced by activated cells, which act by binding high affinity cell surface receptors. They are involved in almost all aspects of cell biology and form interacting networks, with cascades of sequential cell activation. They often show overlapping activities ( redundancy ) or the same cytokine may have a variety of different effects (pleiotropy). In excess, certain cytokines are damaging and proinflammatory. Tumour necrosis factor a (TNFα) and interleukin-I (IL-I) are markedly proinflammatory, inducing bone resorption, collagenase and prostaglandin E₂ production.
OBJECTIVE: This paper focuses on the role of TNFa and IL-l in the cytokine networks of destructive chronic per-iodontitis; specifically their regulation by T cell cytokines, receptor antagonists and inhibitory soluble forms of the IL-l and TNF receptors.
CONCLUSION: A hypothesis is proposed that destructive periodontal disease may be due to disregulation of these inhibitors, rather than an overproduction of IL-l and TNFα per se.     

氟化钠、单氟磷酸钠漱口后2 h菌斑液、菌斑及唾液氟离子的测定

氟化钠(NaF)和单氟磷酸钠(NaMFP)是目前市售最常见的含氟牙粉。以前一致认为氟的抗龋效能取决于牙所处液体环境中Fˉ浓度,但其临床抗龋效果却与二者的Fˉ浓度出现较大差异。本研究定量分析NaF和NaMFP液漱口后,唾液、全菌斑及菌斑液中Fˉ、MFPˉ浓度的变化,揭示其不同的抗龋特性。 标本取自12位自愿受试者。每个象限各选一颗磨牙或前磨牙取菌斑。测前48h不刷牙,当晚禁食,次日上午收集龈下菌斑和唾液标本作为基线水     

Induction Of Endothelin-1 Expression By Glucose: An Effect Of Protein Kinase C Activation

Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have been associated with decreased blood flow in the retina and peripheral nerves of diabetic animals and may be related to the development of pathologies in these tissues. Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells. We have characterized the mechanism by which elevation of glucose is increasing ET-1 mRNA expression in capillary bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5 mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. By immunoblot analysis, PKC-beta 2 and -delta isoforms in BREC were significantly increased relative to other isoforms in the membranous fractions when glucose level was increased. Overexpression of PKC-beta 1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy.     

Early Electrophysiological Changes In Transgenic Rat Model Of Charcot-Marie-Tooth

Recently, a reliable transgenic rat model of human Charcot-Marie-Tooth type 1 A has been developed. So far, neurophysiological studies have been performed only in advanced stages of rat disease. Moreover, axonal involvement, which is known to occur in human CMT1A, has never been observed in this rat model. Affected rats show overexpression of Peripheral Myelin Protein (PMP-22) and a peripheral hypomyelinating neuropathy. We perfomed an electrophysiological study in two heterozygous PMP-22 transgenic rats and in one normal control, matched for age (3 weeks) and weight (average: 60 g). Recordings were performed in vivo by stimulating the sciatic nerve at both sciatic notch and ankle sites and recording the Hoffman reflex and direct muscle responses (CMAP). The H-reflex related SNCV and MNCV were calculated by measuring the distance between the sciatic notch and the ankle sites and the respective latencies. The two transgenic rats showed different levels of PMP-22 overexpression, as judged by quantitative PCR. The rat with a lower PMP-22 gene level showed a 30% reduction of MNCV compared to the normal control, while SNCV was not reduced. The CMAP was sized approximately 45% of the normal rat while the ratio between H wave amplitude and CMAP was 30% of the normal, the H wave amplitude being more affected than the CMAP. The action potentials in the rat with a higher transgene level were not recordable. Our data demonstrate that slowing of MNCV is an early finding in the CMT1A rat model. The marked reduction of H wave amplitude in front of a normal SNCV suggests a possible early axonal damage of sensory fibers. The entity of electrophysiological compromission positively correlated with the number of copies for PMP-22 gene. All together these considerations prove the sensitivity of this method, however further studies are needed to confirm these results and to prove that this model may be suitable to investigate the effects of therapeutic approaches.     

Familial Cushing's disease with severe weight loss occurring in late childhood

We describe a rare case of familial Cushing's disease occurring in a 7-year-old boy, and 19 years of follow up. Our patient first presented soon after his maternal aunt had been treated for Cushing's disease. The clinical presentation was made complicated by the development of an intercurrent eating disorder resembling anorexia nervosa. This resulted in marked weight loss, and even though serum and urinary cortisol levels were elevated, many of the clinical stigmata of Cushing's disease were absent. Eating disorders are relatively uncommon in boys, and in this case there was an organic cause for the abnormal behaviour. This case shows, furthermore, that even the obesity of Cushing's disease can be overcome by the combination of diet and exercise.     

Ascorbate-2-phosphate in red cell preservation. Clinical trials and active components

A red cell additive solution (AS-005) containing ascorbate-2-phosphate (AsP) to maintain 2,3-diphosphoglycerate, plus adenine, phosphate, and mannitol to retain viability and reduce hemolysis, was evaluated by human clinical trials. A crossover design was used with another additive solution (Nutricel AS-3, Cutter Laboratories) serving as the control for each donor. Each additive solution was evaluated at 35 and 42 days of storage. There was no significant difference between the red cell viability of the two storage solutions at either time period. Split-bag, AS-005 in vitro studies at two temperatures (2.5 and 5.5 degrees C), both within the range of 1 to 6 degrees C approved by the American Association of Blood Banks and the Food and Drug Administration, resulted in dramatically different in vitro parameters, including a threefold difference in 2,3-diphosphoglycerate (2,3-DPG), a fivefold difference in glucose, and significant differences in pH and adenosine triphosphate. High-pressure liquid chromatography data confirmed the preliminary report that 1 to 2 percent (wt/wt) oxalate was present in preparations of AsP. In vitro storage data confirmed that oxalate is the active component of AsP that preserves 2,3-DPG during storage.