Effect of the NSAID flurbiprofen on remodelling after periodontal surgery

The aim of the present experiment was to assess the effect of the administration of the NSAID flurbiprofen (Froben®) on tissue healing after periodontal surgery. Sites from patients with the same treatment modality (modified Widman flap) but receiving a placebo drug and sites within each patient not exposed to surgery served as controls. Nineteen patients suffering from moderate to severe periodontal disease were recruited and they signed informed consent forms. These patients required periodontal surgery as assessed at the periodontal re-evaluation. The sites chosen for the study were all diagnosed with PPD ≥ 5 mm and were bleeding on probing. During the healing phase 10 patients received 50 mg Froben® 3 times per day for 30 d whereas 9 patients received a placebo drug. Two sites with PPD ≥ 5 mm after initial therapy and bleeding on probing served as surgical sites, whereas 2 similar sites were not exposed to surgery. The study design was set up double-blind. The radiographic examination consisted of 2–4 standardized vertical bitewings obtained at the periodontal re-evaluation (BL) at 1, 3 and 6 months post-surgically for digital subtraction and computer assisted densitometric image analysis (CADIA). The regions of interest analysed were mesial or distal crestal sites. Minimal remodelling activity was observed radiographically after periodontal surgery in both patient groups. There were no statistically significant differences between the four groups of sites regarding the mean changes in density when analysing the pairs of radiographs 0–1, 0–3, 0–6 months. A frequency analysis was performed to list the number of sites with different ranges of density change. No differences in the distributions of the numbers of sites were observed when comparing the 4 site groups (Kolmogorov-Smirnov, p > 0.05). A significant reduction of the probing pocket depth and a significant amount of clinical attachment gain was noted at the surgically treated sites irrespective of whether the patients had used flurbiprofen or placebo. Whereas the pathways leading to bone resorption in periodontally diseased sites have been shown, in other studies, to be influenced by NSAID, the results of the present study could not justify general administration of Froben® for the purpose of reduction of bone resorption after periodontal surgical procedures in patients with adult periodontitis.     

Effect of erythropoietin on blood pressure and on the vascular endothelial ET-1/ETB receptor system

BACKGROUND: Recombinant human erythropoietin (rhEPO) increases blood pressure (BP) and the vascular production of endothelin-1 in renal failure rats. This study was designed to investigate the effect of rhEPO on BP and on the ET-1/ET(B)R system in rats with normal renal function. To further characterize the effect of rhEPO on the ET-1/ET(B)R system, we also studied heterozygous (+/-) ET(B)R knockout (KO) mice. METHODS: The animals received either the vehicle or rhEPO (100 U/kg subcutaneously three times per week). ET(B)R(+/-) mice were compared with ET(A)R(+/-) and wild-type (WT) mice. In rats, the ET(B)R mRNA expression was assessed in blood vessels as well as the vascular ET(B)R density using immunohistochemistry. In mice, ET-1 concentration was measured in the thoracic aorta. RESULTS: RhEPO administration increased hematocrit levels in all treated animals. This therapy had no effect on BP in normal rats, but it did increase vascular and renal cortex ET(B)R mRNA expression. Immunohistochemistry confirmed that the ET(B)R density was increased in blood vessel endothelium in these normal rats. In contrast, rhEPO increased BP in ET(B)R(+/-) mice and this pressor effect was associated with higher ET-1 concentrations in the thoracic aorta. CONCLUSIONS: RhEPO exerts a pleotropic effect on the endothelial ET-1/ET(B)R system. The increase in endothelial ET(B)R expression may contribute to maintaining normal BP during rhEPO administration in normal animals. Conversely, conditions with deficient ET(B)R expression, such as in ET(B)R(+/-) mice, may lead to hypertension while receiving the same therapy.     

Increased Acid Sphingomyelinase Activity in Peripheral Blood Cells of Acutely Intoxicated Patients With Alcohol Dependence

Background:  Acid sphingomyelinase (ASM; EC 3.1.4.12) hydrolyses membrane sphingomyelin into the bioactive lipid ceramide and is thus involved in different cellular processes such as differentiation, immunity, or cell death. Activation of ASM has been reported in particular in conjunction with the cellular stress response to several external stimuli, and increased ASM activity was observed in a variety of human diseases. Ethanol-induced activation of ASM has been observed in different cell culture systems, thus raising the question about the effect of alcohol intoxication in human subjects on ASM activity in vivo.
Methods:  We determined ASM activity in peripheral blood mononucleated cells of 27 patients suffering from alcohol dependence. Patients were classified according to their blood alcohol concentration at admission, and ASM activity was determined repeatedly from all patients during alcohol withdrawal.
Results:  Acutely intoxicated patients displayed significantly higher ASM activity than patients in early abstinence (Mann–Whitney U test: Z  = − 2.6, p  = 0.009). ASM activity declined in acutely intoxicated patients to normal values with the transition from the intoxicated state to early abstinence (Wilcoxon test: Z  = −2.7, p  = 0.007). At the end of withdrawal, ASM activity was significantly increased again compared to the early phase of abstinence in both patient groups (Wilcoxon test: Z  = −2.691, p  = 0.007 and Z  = −2.275, p  = 0.023, respectively).
Conclusions:  Alcohol-induced activation of ASM occurs in human subjects and might be responsible for deleterious effects of ethanol intoxication. Chronic alcohol abuse may induce deregulation of sphingomyelin metabolism in general, and this impairment may cause side effects during withdrawal from alcohol.     

Liver transplantation for fulminant hepatic failure in infancy: A single center experience

Abstract:  FHF is characterized by a high percentage of unknown causes leading to acute liver failure and furthermore by an increased morbidity and mortality prior to and post-Ltx. In different transplant centers, the reasons leading to FHF differ significantly as well as outcome. We report our single center experience with 30 pediatric patients receiving a liver transplant for FHF, out of a total of 83 children presenting with FHF. The time to transfer patients to the transplant center after the diagnosis of FHF was long, with a median of 14 days (Ltx group) and 12 days (controls), respectively. In nearly half of the patients (n = 14) in the Ltx group, we were not able to establish an exact diagnosis prior to Ltx: 50% suffered from encephalopathy, and 13 patients were treated in the intensive care unit prior to transplant. Because of the availability of different surgical techniques, all children received a timely transplant [split (n = 18), living donor (n = 9), whole organ (n = 2), and reduced liver (n = 1)]. Patient survival was 93.4%, and graft survival was 83.4% for at least one yr follow-up. Severe complications following Ltx included three cases with aplastic anemia and one child suffering from systemic mitochondrial depletion syndrome. The survival of patients treated medically was 83%. We conclude that a strong focus should be made on early referral to a specialized center and on improvement of diagnostic tools to timely detect the underlying reason for FHF. Results following Ltx for FHF are good.     

Hypothyroidism in neonates post-iodinated contrast media: a systematic review

Aim: To determine if neonates exposed to iodinated contrast media are at risk of hypothyroidism. Methods: A systematic review was conducted by searching electronic databases (e.g. MEDLINE), contacting experts and scanning reference lists. Studies examining the effects of contrast media on neonatal thyroid function were included. Two reviewers independently screened the literature and assessed the risk of bias, while one reviewer abstracted data. Results: Eleven studies were included; nine studies directly examined the risk of hypothyroidism (n = 182 neonates exposed to contrast media). All were highly affected by bias. In the three studies including term infants, one showed a trend towards increased thyroid‐stimulating hormone (TSH) and decreased free thyroxine (FT4) among exposed groups. Six of 72 (8.3%) term infants exposed were treated for hypothyroidism. In studies of premature infants, there was a trend towards increased TSH (n = 3/7 studies), lower total thyroxine (n = 1), decreased triidothyronine and FT4 (n = 3) and hypothyroidism (n = 5). Twenty of 110 (18.2%) premature infants exposed were treated for hypothyroidism. Conclusion: Hospitalized neonates exposed to iodinated contrast media are at risk for abnormal thyroid function and development of hypothyroidism. Premature infants might be at increased risk. Well‐controlled studies are required to replicate our findings because the included studies were highly affected by bias.     

Ehlers-Danlos syndrome type IV caused by Gly400Glu, Gly595Cys and Glyl003Asp substitutions in collagen III: clinical features, biochemical screening, and molecular confirmation

Three patients with Ehlers-Danlos syndrome type IV (EDS IV) and biochemical evidence of structural defects in collagen III were investigated for mutations within the collagen III gene ( COL3A1 ). Single strand conformation polymorphism analysis of α1(III) cDNA indicated the presence of different heterozygous sequence changes in each of the patients. Nucleotide sequencing revealed mutations leading to the substitution of glycine 400 with glutamic acid, glycine 595 with cysteine, and glycine 1003 with aspartic acid. EDS IV is a life-threatening disorder which, as the clinical histories of our patients and their families show, still often escapes diagnosis. Biochemical and molecular studies can clarify the diagnosis and help provide appropriate management and counselling.     

Humoral immune response to the capsid components of recombinant adenoviruses: Routes of immunization modulate virus-induced Ig subclass shifts

This study examines in detail the capsid-specific humoral immune response of BALB/c mice after one single injection of a replication-defective adenovirus. Two routes of immunization, intravenous (i.v.) and intraperitoneal (i.p.), were compared for the response induced against the adenovirus particle and the three major components of the viral capsid, hexon, penton base, and fiber. A single immunization with the replication-defective adenovirus induces a long and persistent humoral response specific for the virus. However, the molecular components of the viral capsid are differentially recognized depending on the route of immunization. The sera from mice immunized i.p. recognized only the hexon protein and a preferential switch to the IgG2a subclass was obtained which remained stable 100 days post-immunization. The sera obtained from mice immunized i.v. gave a more complex response. At the beginning of the response, an isotype bias toward the IgG2a subclass was observed, but the isotype distribution changed during the whole period of the response. Neutralizing activity was maximum 45 days after immunization by both routes, and no activity was detectable after 3 months. However, the i.v. serum displayed a higher neutralizing activity than the i.p. serum. The IgM antiviral antibodies appeared to be an important component of the neutralizing activity, and the two routes of immunization do not induce the same IgG isotypes to neutralize viral infectivity. Extension of these findings to human gene therapy using recombinant adenoviruses may help to characterize the precise viral protein targets of neutralizing antibodies.     

Indirect Determination of Dichlorodiphenyltrichloroethane (DDT) After Dechlorination with Magnesium/Palladium Bimetallic Particles and Potentiometric Measurements

Determination of chlorine ions of pesticides was performed after dechlorination reaction using a palladium/magnesium system. Chlorine ions were quantified by potentiometry with ion-specific electrode. Rates of dechlorination of 100 μg of DDT as a function of reaction time and percent (wt/wt) of palladium deposited on the magnesium particles were determined. The best reaction conditions to DDT dechlorination were achieved with an acetone/water (1:1) solution and DDT reaction with a 0.27% (wt/wt) palladium/magnesium bimetallic system at room temperature for 10 min. The detection limit was of 0.24 μg/mL. This low cost method showed an efficiency of 92% in determining chlorine ions derived from DDT, it is fast, requiring no specialized laboratory equipment.     

Insulin-like factor 3 as a marker of testicular function in obese men

Objectives  Testicular function declines with obesity as a result of central and peripheral mechanisms, including a primary dysfunction of the Leydig cells. The levels of insulin-like factor 3 (INSL3), a sensitive marker of Leydig cell impairment, have never been evaluated in obese men. To better evaluate the hormonal function of the testis in obese men, we analysed their INSL3 plasma levels and compared them with the obesity status and the other reproductive hormones.
Design  Cross-sectional study.
Patients  Thirty-one obese men [body mass index (BMI) >30 kg/m²) aged 22–49 years and 64 age-matched nonobese men.
Measurements  Plasma concentrations of INSL3, testosterone (T), sex hormone-binding globulin (SHBG), oestradiol (E₂), LH, FSH. Free testosterone (FT) levels were calculated.
Results  Obese men had significantly lower plasma concentrations of total T, SHBG, FT and INSL3, and higher levels of E₂ with respect to nonobese men. LH and FSH values were not different from controls. In obese men, we found a significant negative correlation between BMI and INSL3, and a positive correlation between INSL3 and T. Only one (1/31, 3·2%) obese man had subnormal T levels. On the contrary, 10/31 (32·3%) obese men had low INSL3 values.
Conclusions  This study showed for the first time that INSL3 levels decrease with obesity, probably as a result of a primary dysfunction of the Leydig cells. INSL3 is a reliable marker of Leydig cell general impairment, whereas T mainly reflects the steroidogenic activity of these cells.