Effect of implant loading protocols on failure and marginal bone loss with unsplinted two-implant-supported mandibular overdentures: systematic review and meta-analysis.

The aim of this study was to compare implant failure and radiographic bone level changes with different loading protocols for unsplinted two-implant-supported mandibular overdentures. An electronic search of two databases (PubMed, Cochrane Library) was performed, without language restriction, to identify randomized controlled trials (RCTs) comparing immediate or early versus conventional dental implant loading protocols for unsplinted two-implant-supported mandibular overdentures. Data were extracted independently by two reviewers. The Cochrane tool was used to assess the quality of included studies. A meta-analysis was performed. Eight RCTs were identified, seven of which were included; one trial was excluded because related outcomes were not measured. Four of the seven studies were considered to have a high risk of bias and three an unclear risk. Meta-analysis revealed no difference between immediate versus conventional or early versus conventional implant loading protocols regarding implant failure (risk difference (RD) -0.02, 95% confidence interval (CI) -0.13 to 0.10; RD 0.09, 95% CI -0.03 to 0.20) or marginal bone loss (mean difference (MD) 0.09, 95% CI -0.10 to 0.28; MD -0.05, 95% CI -0.12 to 0.02) for implants supporting mandibular overdentures. These findings should be interpreted with great caution given the serious numerical limitations of the studies included.

Activities of cyclooxygenases, and levels of prostaglandins E2 and F2alpha, in fetopathy associated with experimental diabetic gestation.

AIM: The present study investigated the cyclooxygenase (COX) pathway to elucidate any changes that may be involved in the mechanism(s) underlying diabetic fetopathy. METHODS: Diabetes was induced in female rats (n=12) by two successive daily injections of 55 mg/kg streptozotocin, while control animals (n=10) were injected with a buffer solution; hyperglycaemia was confirmed by blood glucose levels greater than 11 mmol/L. The study female rats were made pregnant and, on day 15 of gestation, the rats were sacrificed, and the fetuses, placentas and membranes dissected out of the uterine horns. Following morphological examination, the fetuses, placentas and membranes were homogenized, and used to measure COX activities and prostaglandin (PG) E(2) and PGF(2alpha) levels. RESULTS: Fetuses from diabetic mothers exhibited significantly (P<0.05) shorter crown-to-rump lengths, lower body weights and heavier placental weights. The activity of COX-1 in the fetuses, placentas and membranes from diabetic mothers represented a small percentage of total COX activity compared with that of COX-2. The presence of a COX-1 inhibitor in the control and diabetic rats was investigated and found to be negative. The activity of COX-2 in malformed fetuses from diabetic mothers was significantly lower (P<0.05) compared with non-malformed fetuses from control and diabetic mothers. The mean level of PGE(2) in fetuses from diabetic mothers was significantly (P<0.05) lower than that in controls. In contrast, the biggest increases in PGF(2alpha) were observed in the malformed diabetic fetuses, placentas and membranes. CONCLUSION: The increased production of PGF(2alpha) probably proceeds, at least in part, independently of the COX pathway and via the isoprostane route. However, it is unclear whether the relatively high levels of PGF(2alpha) are causally related to, or simply coincidental with, fetal malformation.

Relationship between level of circulating modified LDL and the extent of coronary artery disease in type 2 diabetic patients.

The impact of diabetes on health is due almost entirely to a series of complications that characterise the disease. It is associated with an increased incidence of macrovascular complications including coronary artery disease (CAD). The aim of the present study is to evaluate the possible relationship between the circulating levels of the modified derivatives of low-density lipoprotein (LDL) and the development of angiopathy in type 2 diabetic patients with CAD. The status of the antioxidant defences and the role of supplementation with antioxidant combinations are also studied in these patients. The study was conducted on three groups: group I (controls); group II (type 2 diabetic patients without complications--CAD[-]); and group III (including type 2 diabetic patients with stable CAD - CAD[+]). Patients in group III received adjunct treatment of antioxidant tablets for three months. The results of the present study clearly indicated that there was excessive exposure to oxidative stress in diabetic patients. The increase in free radicals was coupled with disturbance in free radical scavengers, particularly the glutathione system. The disturbance was more prominent in CAD(+) patients. The study has shown alteration in the lipid profile in diabetic groups, where the oxidised LDL (ox-LDL) levels were significantly higher than in control subjects. Diabetics with CAD had higher levels of ox-LDL than did patients without CAD. The intima/media thickness (IMT) of the carotid artery was within clinically accepted normal values if the ox-LDL level was below 100-110 u/L. Once the ox-LDL exceeded this range, IMT increased sharply with the increase in plasma ox-LDL. It seems that the level of ox-LDL should be kept below an upper limit of the 100-110 u/L range in order to avoid the serious atherosclerotic effects of this factor. The results demonstrate that plasma levels of ox-LDL correlate with the extent of coronary artery disease in type 2 diabetic patients and suggest that elevated levels of ox-LDL, can serve as an independent and significant predictor for future cardiac events in type 2 diabetic patients with CAD.

Modulation of the antioxidant defence in different developmental stages of Schistosoma mansoni by praziquantel and artemether.

Human schistosomiasis is a chronic and debilitating parasitic disease caused by parasitic trematode worms (schistosomes). Praziquantel (PZQ) is the drug of choice as it is active against all Schistosoma species, can be administered easily, has high cure and egg reduction rates, with no or only mild side effects. Rapid re-infection following treatment and the concerns about PZQ resistance has led to the search for new drugs to treat schistosomiasis. Significant progress has been made with artemisinin derivatives (e.g., artemether [ART]) that are used for chemoprophylaxis. This present study aims to look at the effects of ART and PZQ on the antioxidant defence of immature (three-week-old) and mature (six-week-old) stages of S. mansoni. The possible development of time- or concentration-dependent changes in oxidative stress is assessed by incubation with different sublethal drug concentrations (50, 75, 100 ng/mL for both ART and PZQ) and different time periods (one and three hours). The results indicated a time- and concentration-dependent depletion of glutathione (GSH), which was greater in the immature worms after incubation with ART. On addition of ART to the incubation medium of mature and immature worms, elevation in lipid peroxidation (TBARS) level was observed, which was time- and concentration-dependent, and more prominent in the immature schistosomes. Addition of PZQ to the incubation medium containing the immature schistosomes did not have a significant effect on TBARS level, except after three hours' incubation with the highest concentration used; however, a significant rise was seen in the mature worms. The PZQ had no effect on the activities of superoxide dismutase (SOD), glutathione peroxidase (tGPx, sGPx and nGPx) and glutathione transferase (GST) in mature or immature worms. While ART induced SOD activity in mature worms, it induced tGPx, nGPx and GST activities in a time- and concentration-dependent manner in both mature and immature worms. Activation was more prominent in the immature schistosomes. The results of the present study indicate that the immature schistosomes are more prone to oxidative killing, which probably participates in the mechanism of antischistosomal action of ART against the immature stage of S. mansoni. The results suggest that the mechanism of schistosomicidal action of PZQ is probably not substantially dependent on oxidative stress or oxidative killing.

Embryopathy in experimental diabetic gestation: assessment of oxidative stress and antioxidant defence.

Maternal diabetes is associated with an increased rate of congenital fetal anomaly. In the present study, diabetes was induced by streptozotocin in female rats one week prior to conception and the embryos were examined during organogenesis. Experimental diabetes is associated with over-production of free radicals and disturbed antioxidant defence, particularly in malformed embryos. Oxidative stress is demonstrated by increased MDA accumulation and reduced glutathione levels. Despite large differences in the reduced/oxidised glutathione ratios during organogenesis in the control, diabetic non-malformed and malformed embryo groups, the half-cell redox potential was constant for each group during the experimental period. Calculated redox potentials indicated that although embryo cells from the control and diabetic mother groups were of the same chronological age, the stages of development were different. Increased oxidative stress in rat embryos was associated with increased glutathione peroxidases and glutathione-S-transferase activity. This may, in part, provide an explanation for the observed accumulation of oxidised glutathione in malformed embryos. Moreover, decreased levels of vitamin C and selenium were observed. Increased oxidative stress and perturbations in antioxidant defence contribute to the high incidence of congenital anomalies in experimental diabetic gestation.

Embryopathy in experimental diabetic gestation: assessment of PGE2 level, gene expression of cyclooxygenases and apoptosis.

The causes of, and predisposing conditions for, increased congenital anomalies in embryos of experimental diabetic gestation are not fully identified. In the present study, some possible factors involved in diabetes-induced embryopathy are explored. The concentration of PGE2, the gene expression of cyclooxygenases (COX-1 and COX-2) and level of apoptosis (measured by caspase-3 activity) are assessed during organogenesis in the embryos of streptozotocin-induced diabetic rats. The concentrations of PGE2 in the embryos of diabetic rats were lower than controls, with the lowest values in malformed embryos and their associated membranes (yolk sacs). The pattern of change in PGE2 was similar in the embryos of the control and diabetic groups, which showed a steady decline between days 9 and 11 of gestation. These changes in PGE2 were accompanied by a small decrease in COX-1 expression in all embryos and associated membranes during the same gestational period. Expression of COX-2, which was below normal in diabetic embryos, decreased between days 9 and 11 of gestation in all groups. In the membranes of non-malformed embryos, COX-2 expression peaked on day 10 of gestation. It was found that there was little or no detectable COX-2 expression in the membranes of malformed embryos on day 9 of gestation and although its expression was detectable on the following days it was much lower than in the other groups. Caspase-3 activity increased substantially between days 9 and 11 of gestation. Embryos from the experimentally diabetic group showed higher activity than did controls, with the largest increases in the malformed embryos. It would appear that COX-2 expression and PGE2 concentration (in both embryo and associated membranes) play a significant role in organ formation. The data presented here suggest that an unhealthy placenta may be instrumental in the development of malformed embryos.

In vitro effect of low concentrations of oltipraz on the antioxidant defence of mouse hepatocytes and Schistosoma mansoni worms.

The direct effects of oltipraz (OPZ) on mouse hepatocytes and Schistosoma mansoni worms are studied in vitro at a concentration range of 5-25 micromol/L following one- and three-hour incubations. Oxidative stress is reflected by increases in malondialdehyde (MDA), representing the end products of lipid peroxidation, and depletion of glutathione (GSH), representing protective thiol groups. Activities of glutathione peroxidase isoenzymes, GST and GR as components of antioxidative defence are also determined. The opposite effects of low concentrations of OPZ on mammalian hepatocytes and S. mansoni worms were confirmed. In incubation with S. mansoni, addition of OPZ resulted in significantly increased production of MDA, together with depletion of GSH, both of which were time- and OPZ concentration-dependent. In incubation with mouse hepatocytes, however, there was little change in MDA concentrations, and a gradual increase in GSH levels, both of which were time- and concentration-dependent. Addition of OPZ to the incubation media also affected the activities of antioxidant enzymes. Although total GPx activity increased in both mammalian hepatocyte and S. mansoni experiments, the opposite was noted with the selenium-dependent isoenzyme. While there was a gradual increase in sGPx in hepatocytes, there was a time- and concentration-dependent inhibition in the worm isoenzyme. Contrasting results were also obtained with GR. While increased activity was obtained with the enzyme from mouse hepatocytes, the worm enzyme was inhibited, especially at the upper end of the OPZ concentration range and also following longer periods of incubation. The increase in GST activity followed the same qualitative pattern in both hepatocytes and schistosomes. Therefore, OPZ given in doses that maintain a serum concentration in the range 5-25 micromol/L induces biochemical changes in mouse hepatocytes that could be utilised for chemo-preventive purposes and prevention of oxidative damage. However, progressive oxidative damage to S. mansoni worms occurred despite some protective biochemical changes.

Nitric oxide generation by peripheral blood cells in chronic renal failure.

Nitric oxide (NO), a labile free radical synthesised from L-arginine by the action of nitric oxide synthase (NOS), is said to be implicated in uraemic complications, such as infection and a tendency to bleed. In this study of NO production by peripheral blood cells, an increased level is seen in platelets from uraemic patients (both non-dialysed and haemodialysed) and a decreased level in leucocytes (neutrophils and monocytes). A negative correlation was noted between blood urea level and inducible NO in neutrophils and monocytes in uraemic patients not on dialysis. In contrast, haemodialysis appears to lead to an increase in inducible NO production in neutrophils and monocytes. Plasma NO levels were significantly increased in uraemic patients, compared with normal controls, and hemodialysis led to further increases. Superoxide dismutase (SOD) activity was significantly reduced in platelets, neutrophils and monocytes in the uraemic group. It is concluded that increased NO production by platelets may contribute to the bleeding tendency observed in uraemia, and high urea concentrations may contribute to the regulation of inducible NO production in leucocytes.

Antioxidants as adjuvant therapy in rheumatoid disease. A preliminary study.

The aim of the present study was to assess the therapeutic value of adding a high dose of vitamin E or an antioxidant combination to the treatment regimen of the rheumatoid disease. The study was carried out on 30 patients with rheumatoid disease diagnosed according to the criteria of American Rheumatism Association (ARA), subvided into three equal groups. Patients in group I received a standard treatment of intramuscular methotrexate (CAS 59-05-2; 12.5 mg/week), oral sulphasalazine (CAS 599-79-1; 0.5 g b.i.d.) and indometacin (CAS 53-86-1; 100 mg suppository at bed-time). In group II the patients received the standard treatment plus a combination of antioxidants. Patients in group III received a high dose of vitamin E (400 mg t.i.d.) in addition to the standard treatment. The disease state was evaluated using Ritchle's articular score index and the duration of morning stiffness. Laboratory evaluations included the rheumatoid factor, erythrocyte sedimentation rate (ESR), plasma levels of vitamin E and malonedialdehyde (MDA), and the activity of glutathione peroxidase (GPx). In the group receiving the standard regimen, the patients started to feel tangible improvement by the end of the second month. With adjuvant therapy of either the antioxidant combination or a high dose of vitamin E the symptoms of arthritis were better controlled from the first month. By the end of the second month, the values of the three monitoring tests were significantly decreased indicating better control of the disease. The percentage increase in the activity of GPx was highest in patients taking the antioxidant combination and least in those taking the standard treatment. The decrease in plasma MDA followed the same pattern. With adjuvant therapy, the vitamin E level in plasma increased with the duration of treatment. The results obtained in the present study are encouraging. The clinical improvement and the shift in the disease indices towards normal make the use of antioxidants as adjuvant therapy in rheumatoid disease worth pursuing.

Effect of selenium supplementation on the activities of glutathione metabolizing enzymes in human hepatoma Hep G2 cell line.

Cell culture is an important tool for studying injury to cells exposed to oxidative stress. The human hepatoblastoma derived Hep G2 cells retain their morphology and most of their function in culture and are therefore widely used as an in vitro model of human hepatocytes. Conventional cell culture media are deficient in selenium, which is essential for activation of glutathione peroxidase (GPx), a key enzyme in the defense against oxidative stress. Supplementation of the culture media with 1 microM sodium selenite increased the activities of total GPx by threefold and the selenium-dependent GPx by fourfold as compared to cells cultured in control media. The non-selenium-dependent GPx activity was unchanged. The activities of the other glutathione (GSH)-related enzymes were practically unchanged despite a tendency toward elevation. The activities of oxidized glutathione (GSSG) reductase and catalase increased by 22.4 and 27.4%, respectively. These relatively small increases did not carry statistical significance. Supplementation of tissue culture media with selenium may prove important, particularly for cell protection against oxidative stress.

Detection of circulating E/S antigens in the sera of patients with fascioliasis by IELISA: a tool of serodiagnosis and assessment of cure.

An IELISA was developed to evaluate the performance of Fasciola E/S antigens in diagnosis and cure assessment of human Fasciola infection. Twenty patients with acute (prepatent) fascioliasis and another 20 with patent infection were enrolled in the study. Patients were treated with TCZ and followed at 1, 3 and 6 months after therapy. At inspection, the sensitivity of the test to diagnose prepatent cases was 100% compared to 70% for patent infections. There was a gradual decrease of antigenaemia over the follow-up period in acute cases. In chronic cases antigen disappeared from 13 cases (65%) at 1 month; this proportion did not change at 3 or 6 months.

Changes in the defense against free radicals in the liver and plasma of the dog during hypoxia and/or halothane anaesthesia.

Defenses against free radicals were evaluated in the dog under different conditions of ventilation. Changes in the levels of reduced glutathione (GSH), alpha-tocopherol (vitamin E), ascorbic acid (vitamin C) and the lipid peroxidation end-products, estimated as malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), were studied in serial liver biopsies from dogs ventilated with either oxygen, halothane and oxygen, hypoxic gas mixture of 8% oxygen and 92% nitrogen or halothane under hypoxic conditions. Simultaneous determination of GSH, vitamin E and MDA were carried out in the plasma. The results showed time-dependent depletion of GSH and vitamin E in liver and plasma and vitamin C in the liver. This was accompanied by a simultaneous increase in the levels of MDA. The magnitude of the change was in the following order: halothane and hypoxia > hypoxia > halothane and oxygen > oxygen. The greatest depletion was observed for vitamin E and the least for vitamin C. The rise in the level of MDA in plasma was much higher than in the liver tissue. Hypoxia resulted in inhibition of liver SOD activity. It seems that increased production of free radicals under hypoxic conditions may have overwhelmed the anti-oxidant defenses in the liver. In addition, the much higher level of MDA in plasma, as compared to liver tissue, may indicate that MDA could have originated in tissues or organs other than the liver and leaked into the blood, indicating possible damage in other locations in the body.

Evaluation of Fasciola excretory-secretory (E/S) product in diagnosis of acute human fasciolosis by IgM ELISA.

Diagnosis of fasciolosis in the acute phase depends on a sensitive and accurate serological test. The present study is an evaluation of the efficacy of excretory-secretory Fasciola gigantica adult worm antigen by IgM ELISA. Thirty eight patients with acute fasciolosis and 14 in the chronic phase together with 23 patients with different parasitic infections were introduced in the study. Seventeen healthy, parasite free individuals, were served as controls. A crude excretory-secretory antigen and its fractions I and II (obtained by gel filtration chromatography on Sephadex G-200) were tested. The crude antigen revealed 100% sensitivity, 94% specificity and 98% accuracy at the cut off level of 0.3 in acute infection. It gave positive results in 77% of chronic cases. Cross reactions with Schistosoma and Toxoplasma were negligible. A significant positive correlation between IHA titres and ELISA O.D. readings was observed. Fractions I and II proved of no diagnostic significance. The test system F. gigantica E/S product by IgM ELISA is highly recommended for diagnosis of acute fasciolosis.

Molecular weight determination of Fasciola antigens specific for diagnosis of acute fascioliasis.

Acute human fascioliasis depends in its diagnosis on detecting specific antibodies in the sera of patients. It was observed that both somatic fraction I and crude E/S products of adult Fasciola gigantica worm gave sensitive and specific results. Using IgM ELISA, the cut off O.D was 0.6 and 0.3 nm. and the accuracy was 93% and 98% for the two antigens respectively. Determination of the molecular weight of these two antigens was undertaken by SDS-PAGE. The molecular weight of the somatic fraction I ranged from 17.5 to 43.9 kd, that of the crude E/S products ranged from 12.5 to 14.7 kd. These results were compored with those of previous works performed on antigens of F. hepatica.