Background: Cigarette smoking is one of the most significant risk factors in the development and further advancement of inflammatory periodontal disease, however, the role of either nicotine or its primary metabolite cotinine in the progression of periodontitis is unclear. This study aimed to investigate the effects of nicotine and cotinine on the attachment and growth of fibroblasts derived from human periodontal ligament (PDL). Methods: Primary cultures were prepared from the roots of extracted premolar teeth. Cells were used at both low (P3 to P5) and high (P11 to P13) passage. Cell numbers were determined over 14 days using either the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide (MTT) assay or with a Coulter counter. Cultures were exposed to culture medium supplemented with 1) 15% fetal calf serum (FCS) only; 2) 1% FCS only; 3) 1% FCS and nicotine (concentration range 5 ng/ml to 10 mg/ml); or 4) 1% FCS and cotinine (concentration range 0.5 ng/ml to 10 µg/ml). Results: Nicotine significantly (P <0.05, by ANOVA) inhibits attachment and growth of low passage cells at concentrations >1 mg/ml and high passage PDL fibroblasts at concentrations >0.5 mg/ml. Cotinine, at the highest concentration used (10 µg/ml), appeared to inhibit attachment and growth of both low and high passage fibroblasts but this was not statistically significant (P >0.05, by ANOVA). Conclusions: Tobacco products inhibit attachment and growth of human PDL fibroblasts. This may partly explain the role of these substances in the progression of periodontitis. J Periodontol 1999;70:518‐525.
A variety of hyperglycaemia-induced secondary metabolic defects have been identified as possible causal factors in the aetiology of the symmetrical sensory polyneuropathy observed in diabetes mellitus. These include polyol pathway flux [1], protein glycosylation [2], oxidative stress [3] and impaired neurotrophic support [4]. Alteration of cytoplasmic calcium homeostasis and calcium signalling might also be responsible for neurodegenerative diabetic complications [5,6]. Studies have shown altered Ca 2+ signalling in response to cell depolarisation in sensory Diabetologia (2002) AbstractAims/hypothesis. In diabetic sensory polyneuropathy the earliest and most severe pathophysiology occurs in neurones with the longest axons. The aim of this study was to characterise a diabetes-induced neurodegenerative marker that was selective for sensory neurones with the longest axons. We studied alterations in calcium homeostasis since this occurs in other neurodegenerative diseases. Methods. Sensory neurones were cultured from control and streptozotocin-diabetic rats, treated with or without human recombinant neurotrophin-3 (hrNT-3), and neurones from L4-L6 dorsal root ganglia (DRG) which exhibit the longest axons in vivo were compared with those from C5-L3 DRG. Fluorescent video-imaging was used to measure cytoplasmic calcium dynamics. Results. Streptozotocin diabetes of 8 to 14 weeks, induced an increase in resting internal Ca 2+ concentration ([Ca 2+ ] i ), from 67 7 nmol/l in small neurones and 79 9 nmol/l in big neurones obtained from control animals to 214 19 nmol/l in small neurones and 273 30 nmol/l in big neurones after 14 weeks of diabetes (p < 0.05) in L4-L6 DRG cultures. Neurones from C5-L3 ganglia and non-neuronal cells were not affected. Treatment of 14-week streptozotocin-diabetic rats with subcutaneous injection of 5 mg/kg NT-3 normalised the increase in resting [Ca 2+ ] i . The amplitudes induced by depolarisation, caffeine and ATP [Ca 2+ ] i responses were reduced in small ( < 30mm diameter) but not big ( > 35mm diameter) neurones of L4-L6 DRG from streptozotocin-diabetic animals; the C5-L3 DRG were not similarly affected and the changes in the L4-L6 DRG were corrected by NT-3 treatment. Conclusions/interpretation. Altered calcium homeostasis could be an early molecular marker linked to the onset of diabetic sensory neuropathy. This neurodegenerative index can be corrected by NT-3 therapy and should encourage further work aimed at understanding the mechanistic basis of these observations. [Diabetologia (2002) 45:560±570]
Toxins produced by staphylococci and enterobacteria isolated from the nasopharynx of cases of sudden infant death syndrome (SIDS) have a lethal effect when injected into chick embryos. If the toxins are progressively diluted the lethal effect disappears, but certain combinations of toxins show synergy so that if sublethal doses are mixed a highly lethal effect is produced. In this paper it is shown that nicotine at very low concentrations (less than that produced in man by 005 cigarettes) potentiates the lethal action of certain SIDS associated bacterial toxins and markedly potentiates the lethal action of synergistic combinations of bacterial toxins. These results could explain, at least in part, why parental smoking increases the risk of SIDS. They also provide further support for the common bacterial toxin hypothesis of cot death. (Arch Dis Child 1995; 73: 549- assessed by a chick embryo bioassay.8 Furthermore when tested in the same system certain combinations of toxins from the same infant show synergy with the result that a lethal effect is produced by very low toxin concentrations.9In this paper we present evidence that nicotine interacts with selected bacterial toxins potentiating the lethal effect of both single toxins and synergistic combinations. This suggests one possible explanation for the role of tobacco smoke in SIDS. MethodsBacterial isolates from the nasopharynx of SIDS cases had been obtained previously and stored at -70°C.10 To prepare toxins the bacteria were grown on a semipermeable membrane overlying a defined agar.8 In this system nutrients from the agar diffuse through the membrane to support surface growth but toxins secreted by the bacteria over a molecular weight of 12 000 are retained on the surface. The growth was then washed from the membrane and centrifuged and filtered to separate toxin secretions from live organisms. The crude toxin preparations were subsequently diluted to a standard optical density and tested for lethality by injection into the chorioallantoic vein of 11 day old embryonated chick eggs. Finally the eggs were incubated and tested for viability after 18 hours.In these experiments a Staphylococcus aureus and Kiebsiella pneumoniae isolated from one case of SIDS and S aureus and Escherichia coli isolated from a second case of SIDS were used. These pairs had been shown to cause lethal synergy in previous experiments. A series of doubling dilutions were prepared for each toxin preparation. Eleven eggs were injected with each dilution and the percentage lethality calculated. In each case a dilution was chosen which gave a low percentage kill; this was the neat concentration used in subsequent experiments.A solution of nicotine was also tested in the eggs in the same way as for the toxin preparations. A range of concentrations from 1 mg/ml to 7-8 pg/ml was tested. A concentration of 800 ng/ml (equivalent to 40 ng/egg)-was found to produce a lethal response in 22% of embryos. This was used as the neatsolution of nicotine.
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