Best clinical practice guidance for treating deep carious lesions in primary teeth: an EAPD policy document.

PURPOSE: The European Academy of Paediatric Dentistry (EAPD) has developed this best clinical practice guidance to help clinicians manage deep carious lesions in primary teeth. METHODS: Three expert groups conducted systematic reviews of the relevant literature. The topics were: (1) conventional techniques (2) Minimal Intervention Dentistry (MID) and (3) materials. Workshops were held during the corresponding EAPD interim seminar in Oslo in April 2021. Several clinical based recommendations and statements were agreed upon, and gaps in our knowledge were identified. RESULTS: There is strong evidence that indirect pulp capping and pulpotomy techniques, and 38% Silver Diamine Fluoride are shown to be effective for the management of caries in the primary dentition. Due to the strict criteria, it is not possible to give clear recommendations on which materials are most appropriate for restoring primary teeth with deep carious lesions. Atraumatic Restorative Technique (ART) is not suitable for multi-surface caries, and Pre-formed Metal Crowns (PMCs) using the Hall technique reduce patient discomfort. GIC and RMGIC seem to be more favourable given the lower annual failure rate compared to HVGIC and MRGIC. Glass carbomer cannot be recommended due to inferior marginal adaptation and fractures. Compomers, hybrid composite resins and bulk-fill composite resins demonstrated similar values for annual failure rates. CONCLUSION: The management of deep carious lesions in primary teeth can be challenging and must consider the patient's compliance, operator skills, materials and costs. There is a clear need to increase the use of MID techniques in managing carious primary teeth as a mainstream rather than a compromise option.

Minimal intervention dentistry for managing carious lesions into dentine in primary teeth: an umbrella review.

PURPOSE: This umbrella review systematically appraised published systematic reviews on Minimal Intervention Dentistry interventions carried out to manage dentine carious primary teeth to determine how best to translate the available evidence into practice, and to provide recommendations for what requires further research. METHOD: An experienced information specialist searched MEDLINE, Embase, Cochrane Database of Systematic Reviews, Epistemonikos, Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, and the NIHR Journals Library. In addition, the PROSPERO database was searched to identify forthcoming systematic reviews. Searches were built around the following four concepts: primary teeth AND caries/carious lesion AND Minimal Intervention Dentistry AND systematic review/meta-analysis. Searches were restricted to English language, systematic reviews with/without meta-analyses published between January 2000 and August 2020. Two reviewers independently screened all titles and abstracts. Interventions included involved no dentine carious tissue removal (fissure sealants, resin infiltration, topical application of 38% Silver Diamine Fluoride, and Hall Technique), non-restorative caries control, and selective removal of carious tissue involving both stepwise excavation and atraumatic restorative treatment. Systematic reviews were selected, data extracted, and risk of bias assessed using ROBIS by two independent reviewers. Studies overlap was calculated using corrected covered area. RESULTS: Eighteen systematic reviews were included in total; 8 assessed the caries arresting effects of 38% Silver Demine Fluoride (SDF), 1 on the Hall Technique (HT), 1 on selective removal of carious tissue, and eight investigated interventions using atraumatic restorative treatment (ART). Included systematic reviews were published between 2006 and 2020, covering a defined time frame of included randomised controlled trials ranging from 1969 to 2018. Systematic reviews assessed the sealing efficacy of fissure sealants and resin infiltration in carious primary teeth were excluded due to pooled data reporting on caries arrest in both enamel and outer third of dentine with the majority of these carious lesions being limited to enamel. Therefore, fissure sealants and resin infiltration are not recommended for the management of dentinal caries lesions in primary teeth. Topical application of 38% SDF showed a significant caries arrest effect in primary teeth (p < 0.05), and its success rate in arresting dental caries increased when it was applied twice (range between 53 and 91%) rather than once a year (range between 31 and 79%). Data on HT were limited and revealed that preformed metal crowns placed using the HT were likely to reduce discomfort at time of treatment, the risk of major failure (pulp treatment or extraction needed) and pain compared to conventional restorations. Selective removal of carious tissue particularly in deep carious lesions has significantly reduced the risk of pulp exposure (77% and 69% risk reduction with one-step selective caries removal and stepwise excavation, respectively). ART showed higher success rate when placed in single surface compared to multi-surface cavities (86% and 48.7-88%, respectively, over 3 years follow-up). CONCLUSION: Minimal Intervention Dentistry techniques, namely 38% SDF, HT, selective removal of carious tissue, and ART for single surface cavity, appear to be effective in arresting the progress of dentinal caries in primary teeth when compared to no treatment, or conventional restorations. There is clear need to increase the emphasis on considering these techniques for managing carious primary teeth as a mainstream option rather than a compromise option in circumstances where the conventional approach is not possible due to cooperation or cost.

The clinical efficacy of pentoxifylline and l-glutamine on ischemia and reperfusion injury in cattle with displaced abomasum: a longitudinal study.

This study aimed to assess the clinical efficacy of pentoxifylline (PTX) and L-glutamine (L-Gln) treatment on ischemia and reperfusion (I/R) injury in the abomasal tissue, acute phase response (APR), oxidative stress (OS), cytokine response, hemostatic, and coagulation disorders in the 96-h period before and after surgery in displaced abomasum (DA) cases. The study sample consisted of 48 dairy cows with DA that were categorized into four groups as group S (Sham group) (9 Left displaced abomasum (LDA)+3 Right displaced abomasum (RDA), group P (PTX) (10 LDA+2 RDA), group G (L-Gln) (10 LDA+2 RDA), and group P+G (PTX+L-Gln) (10 LDA+2 RDA). Acute-phase protein (Haptoglobin), oxidative stress indicators (malondialdehyde, nitric oxide, and glutathione), cytokines (tumor necrosis factor (TNF)-α and interleukin-1ß (IL-1ß), coagulation factors (D-Dimer, Antithrombin (ATIII), Thrombin-antithrombin complex, Plasminogen activator inhibitor-1), and enzyme activities (lactate dehydrogenase, gamma- -glutamyl transferase, sorbitol dehydrogenase, glutamate dehydrogenase, adenosine deaminase, myeloperoxidase, and creatine phosphokinase) in blood serum samples and coagulometric analyses of blood plasma were performed in samples taken before the operation and at 30 and 60 min and 2, 5, 10, 24, 48, 72, and 96 h after the operation. In DA cases, while post-operative treatment procedures with PTX and L-Gln were effective in decreasing APR and OS, these were ineffective in prohibiting the inflammatory response coordinated by cytokines. For the treatment and prevention of I/R injury in the DA cases, PTX and L-Gln procedures hold promise with their effects on APR, OS, and hemostatic dysfunction. Additional treatment procedures are required for the suppression of inflammatory response, and the effectiveness of preconditioning treatment may be evaluated.

Mechanical reduction in intracanal Enterococcus faecalis when using three different single-file systems: an ex vivo comparative study.

AIM: To evaluate the bacterial reduction achieved by WaveOne Gold (Dentsply Sirona Endodontics, Ballaigues, Switzerland), Hyflex EDM (Coltene-Whaledent, Altstätten, Switzerland), and XP-endo Shaper (FKG Dentaire SA, La Chaux-de-Fonds, Switzerland) in canals infected with Enterococcus faecalis. The null hypothesis (H0 ) was that there would be no difference amongst the NiTi systems in reducing the root canal bacterial load. METHODOLOGY: Seventy-four mandibular premolar teeth with straight and round root canals were selected. Sixty-two root canals were contaminated with E. faecalis for 4 weeks and subjected to mechanical preparation with one of three single-file NiTi rotary systems (WaveOne Gold, Hyflex EDM, and XP Endo Shaper). Twelve non-contaminated root canals were used as negative controls. Bacterial samples were collected with sterile paper points (Dentsply Sirona Endodontics) before and after rotary instrumentation to quantify the bacterial load. Five roots from each instrumentation group were evaluated topographically from the coronal, middle and apical thirds by SEM. The bacterial reduction was calculated and analysed statistically by the Kruskal-Wallis and Dunn post hoc tests, all at 5% significance. RESULTS: The samples taken before instrumentation showed approximately 9.64 log CFU bacterial load. Instrumentation with the Hyflex EDM and XP-endo Shaper resulted in significantly greater bacterial reduction than those with WaveOne Gold (P = 0.00). All specimens had bacterial growth. SEM images supported the CFU/mL data. Thick and dense debris was observed in WaveOne Gold samples. Instrumentation resulted in the disruption of the biofilm-like structure, and both areas of clean and open dentinal tubules and areas with thick debris were observed in Hyflex EDM and XP-endo Shaper samples. CONCLUSIONS: Instrumentation in straight and round canals of premolar teeth with the Hyflex EDM and XP-endo Shaper resulted in significantly greater bacterial reduction than WaveOne Gold. No instrumentation system rendered root canals completely free from bacteria.

The evaluation of hemostatic dysfunction and disseminated intravascular coagulation in dairy cows with abomasal displacement.

Disseminated intravascular coagulation (DIC) is a complex, dynamic and hemostatic disorder which develops secondarily to a disease characterized with an imbalance in the pro-coagulant and anti-coagulant components of hemostasis. The aim of the study is to evaluate hemostatic dysfunc- tion and the DIC syndrome in cattle with displaced abomasum (DA), with using the hematologic analyses and an extensive coagulation profile in the 96 hour-period including before and after surgery. The animal material of the study consisted of 12 dairy cows diagnosed with displaced abomasum (9 LDA and 3 RDA without volvulus) in the 2-4 week period after parturation and with no other post-partum disease. In dairy cows diagnosed with DA, hematological, coagulomet- ric (PT, APTT, Fibrinogen) and coagulation factor analyses [D-Dimer, TAT (thrombin-anti- thrombin complex), ATIII (antithrombin III), PAI-1 (plazminogen activator inhibitor-1] were performed in blood samples obtained before the operation as well as 30 minutes, 60 minutes and 2, 5, 10, 24, 48, 72 and 96 hours after the operation. In the DA cases, abnormalities were found in 6 of the 8 coagulation parameters. In the LDA and RDA groups, prolonged PT (sec), PT (INR) and APTT, hypofibrinogenemia, an increase in serum D-Dimer concentration at 72 and 96 hours after the operation and an increase in serum ATIII concentrations before and 30, 60 minutes and 2, 5, 72 and 96 hours after the operation was found (p⟨0.05). Hemostatic dysfunction and the risk of DIC developing in DA cases and continuing in the post-operative period was determined.

Reporting and Methodological Quality of Randomised Controlled Trials in Vascular and Endovascular Surgery.

BACKGROUND: Randomised controlled trials (RCTs) are subject to bias if they lack methodological quality. Moreover, optimal and transparent reporting of RCT findings aids their critical appraisal and interpretation. OBJECTIVES: The aim of this study was to ascertain whether the methodological and reporting quality of RCTs in vascular and endovascular surgery is improving. METHODS: The most recent 75 and oldest 75 RCTs published in leading journals over a 10-year period (2003-2012) were identified. The reporting quality and methodological quality data of the old and new RCTs were extracted and compared. The former was analysed using the Consolidated Standards of Reporting Trials (CONSORT) statement, the latter with the Scottish Intercollegiate Guidelines Network (SIGN) checklist. RESULTS: Reporting quality measured by CONSORT was better in the new studies than in the old studies (0.68 [95% CI, 0.66-0.7] vs. 0.60 [95% CI, 0.58-0.62], p < .001); however, both new and old studies had similar methodological quality measured by SIGN (0.9 [IQR 0.1] vs. .09 [IQR: 0.2], p = .787). Unlike clinical items, the methodological items of the CONSORT statement were not well reported in old and new RCTs. More trials in the new group were endovascular related (33.33% vs. 17.33%, p = .038) and industry sponsored (28% vs. 6.67%, p = .001). CONCLUSIONS: Despite some progress, there remains room for improvement in the reporting quality of RCTs in vascular and endovascular surgery. The methodological quality of recent RCTs is similar to that of trials performed >10 years ago.

Acute-phase proteins, oxidative stress and enzyme activities of blood serum and peritoneal fluid in cattle with abomasal displacement.

BACKGROUND: Blood serum and peritoneal fluid acute-phase proteins, oxidative stress indicators, and some enzymes could be used for evaluation of abomasal tissue damage because of displacement in displaced abomasum (DA) cases. OBJECTIVES: The aim of this study was to investigate the concentrations of acute-phase proteins, oxidative stress indicators, and activities of enzymes in blood serum and peritoneal fluid in cattle with right displaced abomasum (RDA) and left displaced abomasum (LDA) and in healthy cows. ANIMALS: A total of 60 Holstein Friesian cows in early lactation were used, 31 with left and 9 with right displaced abomasum without volvulus diagnosis and no other postpartum disease, and 20 healthy cows as a control. MATERIALS AND METHODS: DA diagnosis in dairy cows consisted of physical examination, laboratory, and specific DA tests. Acute-phase proteins, oxidative stress indicators, and enzyme activities were measured in blood serum and peritoneal fluid. RESULTS: In the RDA group, serum haptoglobin (HPG), serum amyloid A (SAA), malondialdehyde (MDA), adenosine deaminase (ADA), myeleperoxidase (MPO), aspartate aminotransferase (AST), creatine kinase (CK, creatine kinase-MB (CK-MB), and gamma-glutamyl transferase (GGT) activity increased significantly, and serum HPG, MDA, ADA, and AST concentrations increased significantly in the LDA group (P < .05). Peritoneal fluid HPG, MDA, ADA, MPO, ALP, GGT, and LDH concentrations increased significantly, whereas NO concentrations reduced significantly in the RDA group, and HPG, MDA, ADA, and TP concentrations increased significantly, whereas concentrations of NO reduced significantly in the LDA group (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: There are acute-phase responses, oxidative stress, and abomasal tissue damage because of displacement in DA cases. Especially, HPG, MDA, ADA, and MPO concentrations can provide specific information to help in understanding these changes.

Odontoblast-like cell numbers and reparative dentine thickness after direct pulp capping with platelet-rich plasma and enamel matrix derivative: a histomorphometric evaluation.

AIM: To collect quantitative information about the numbers of odontoblast-like cells and reparative dentine thickness after direct pulp capping with platelet-rich plasma (PRP) and enamel matrix derivative (EMD). METHODOLOGY: The experiment was conducted on 36 Wistar albino rats and a total of 144 incisor teeth. Calcium hydroxide, mineral trioxide aggregate, PRP and EMD were applied as direct capping agents on the pulps of 96 incisors (n = 24). Positive and negative control groups were created on the remaining 48 incisors. The teeth were extracted on the 7th and 28th days. After routine histological preparation, cross-sections were stained with haematoxylin and eosin. The numbers of the odontoblast-like cells were measured histomorphometrically on day 7 and day 28. The thickness of the reparative dentine was also measured. The number of odontoblast-like cells was also measured beneath the dentine bridge. The normal distribution of all data was tested with the Mann-Whitney U test. The statistical differences between groups were analysed using the Kruskal-Wallis test. RESULTS: The mean number of odontoblast-like cells increased between day 7 and 28 following pulp exposure (P > 0.01) in all groups except for the EMD group (P < 0.01), when compared with both the experimental and negative control groups (P < 0.01). Reparative dentine formation was observed in all groups of teeth (P > 0.01). CONCLUSIONS: Reparative dentine formation was observed, but with no significant difference between the groups. Odontoblast-like cells were observed in association with the outcome of pulps capped with PRP and EMD. PRP and EMD are possible capping agents that influence the thickness of reparative dentine formation.

Retinoic acid receptor-α signalling antagonizes both intracellular and extracellular amyloid-ß production and prevents neuronal cell death caused by amyloid-ß.

Alzheimer's disease (AD) is characterized by amyloid-ß (Aß) deposition in the brain, neuronal cell loss and cognitive decline. We show here that retinoic acid receptor (RAR)α signalling in vitro can prevent both intracellular and extracellular Aß accumulation. RARα signalling increases the expression of a disintegrin and metalloprotease 10, an α-secretase that processes the amyloid precursor protein into the non-amyloidic pathway, thus reducing Aß production. We also show that RARα agonists are neuroprotective, as they prevent Aß-induced neuronal cell death in cortical cultures. If RARα agonists are given to the Tg2576 mouse, the normal Aß production in their brains is suppressed. In contrast, neither RARß nor γ-agonists affect Aß production or Aß-mediated neuronal cell death. Therefore, RARα agonists have therapeutic potential for the treatment of AD.

Radiculomegaly of permanent canines: report of endodontic treatment in OFCD syndrome.

AIM: To present a case describing the endodontic treatment of a permanent canine with radiculomegaly and to draw the attention of the endodontic community to this rare anomaly. SUMMARY: Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked dominant syndrome characterized by canine teeth with extremely large roots (radiculomegaly), dental abnormalities, congenital cataracts, dysmorphic facial features and congenital heart disease. The diagnosis of this syndrome is difficult. Unique and specific symptoms, which can be diagnosed by an endodontist or a general dentist, are present in the dental, skeletal, ocular and cardiac structures. Worldwide, only 20 cases of this syndrome have been reported to date. The patient presented in this study was a 17-years-old girl with a mandibular right canine (47.5mm) tooth with two canals. KEY LEARNING POINTS: • Clinicians should be aware of anatomical variations in cases with OFCD syndrome. • Root canal treatment in such cases is challenging. • In general, the majority of mandibular canines have one root and root canal, but 15% may have two canals, and a smaller number may have two distinct roots.

Retinoid induction of alveolar regeneration: from mice to man?

The use of retinoids to induce human lung regeneration is under investigation in a number of studies in patients with chronic obstructive pulmonary disease (COPD). Retinoic acid (RA) has complex pleiotropic functions during vertebrate patterning and development and can induce regeneration in a number of different organ systems. Studies of retinoid signalling during lung development might provide a molecular basis to explain pharmacological induction of alveolar regeneration in adult models of lung disease. In this review the role of endogenous RA signalling during alveologenesis is explored and data suggesting that a number of exogenous retinoids can induce regeneration in the adult lung are discussed. Current controversies in this area are highlighted and a hypothesis of lung regeneration is put forward. Understanding the cellular and molecular mechanisms of induction of regeneration will be central for effective translation into patients with lung disease and may reveal novel insights into the pathogenesis of alveolar disease and senescence.

Radiographic technical quality of root fillings performed by dental students in Turkey.

AIM: To evaluate the radiographic technical quality of root fillings performed by undergraduate students at a dentistry faculty in Turkey. METHODOLOGY: A random sample of 2000 records of patients who received dental treatment at the Faculty of Dentistry, University of Gazi between 2000 and 2003 was investigated. The final sample consisted of 1,893 root-filled teeth with 3,692 root canals in 1,654 dental patients. For each root-filled tooth, at least three periapical radiographs were examined: preoperative, working length determination and postoperative. The length, density and taper of root fillings were recorded. The length of root fillings was recorded as adequate, short or overfilled. Density of root fillings was recorded as adequate or inadequate. Taper of root fillings was recorded as adequate or inadequate. Results were evaluated statistically using one-way analysis of variance (anova) and chi-square analysis. RESULTS: Sixty-nine per cent, 53.2% and 68.3% of root fillings had adequate length, density and taper, respectively; only 33% of teeth fulfilled these three criteria at the same time. The relationship between the length, density and taper of the root filling and the presence of canal curvature was statistically significant (P < 0.001). There was no significant difference between maxillary and mandibular teeth according to the adequacy of the root fillings. The highest percentage of adequate root fillings was found in maxillary canines (51.5%). CONCLUSIONS: The percentage of adequate root fillings performed by undergraduate students was only 33%.

Retinoic acid induces alveolar regeneration in the adult mouse lung.

Recent data suggests that exogenous retinoic acid (RA) can induce alveolar regeneration in a mouse and a rat model of experimental emphysema and disrupted alveolar development. This may be because RA is required during normal alveolar development and the subsequent provision of RA reawakens the gene cascades used during development. Here, additional evidence that RA is required during alveologenesis in the mouse is provided by showing that disulphiram disrupts this process. A further model of disrupted alveolar development using dexamethasone administered postnatally is then described, and it is further shown that RA administered to these adult mice restores the lung architecture to normal. Alveolar regeneration with retinoic acid may therefore be an important novel therapeutic approach to the treatment of respiratory diseases characterised by a reduced gas-exchanging surface area, such as bronchopulmonary dysplasia and emphysema.

The role of retinoic acid in the morphogenesis of the neural tube.

We have examined the role of the signalling molecule, retinoic acid, in the process of neurulation and the subsequent growth and differentiation of the central nervous system using quail embryos that have developed in the absence of retinoic acid. Such retinoic acid-free embryos undergo abnormal neural tube formation in terms of its shape and structure, but the embryos do not display spina bifida or exencephaly. The neural tubes have a wider floor plate, a thicker roof plate and a different dorsoventral shape. Phalloidin staining and electron microscopy revealed alterations in the actin filaments and the junctional complexes of the cell layer lining the lumen. Initially the neural tubes proliferated at the same rate as normal, but later the proliferation rate declined drastically and neuronal differentiation was highly deficient. There were very few motoneurons extending neurites into the periphery, and within the neural tube axon trajectories were chaotic. These results reveal several functions for retinoic acid in the morphogenesis and growth of the neural tube, many of which can be explained by defective notochord signalling, but they do not suggest that this molecule plays a role in neural tube closure.

Too much of a good thing: retinoic acid as an endogenous regulator of neural differentiation and exogenous teratogen.

Retinoic acid (RA) is essential for both embryonic and adult growth, activating gene transcription via specific nuclear receptors. It is generated, via a retinaldehyde intermediate, from retinol (vitamin A). RA levels require precise regulation by controlled synthesis and catabolism, and when RA concentrations deviate from normal, in either direction, abnormal growth and development occurs. This review describes: (i) how the pattern of RA metabolic enzymes controls the actions of RA; and (ii) the type of abnormalities that result when this pattern breaks down. Examples are given of RA control of the anterior/posterior axis of the hindbrain, the dorsal/ventral axis of the spinal cord, as well as certain sex-specific segments of the spinal cord, using varied animal models including mouse, quail and mosquitofish. These functions are highly sensitive to abnormal changes in RA concentration. In rodents, the control of neural patterning and differentiation are disrupted when RA concentrations are lowered, whereas inappropriately high concentrations of RA result in abnormal development of cerebellum and hindbrain nuclei. The latter parallels the malformations seen in the human embryo exposed to RA due to treatment of the mother with the acne drug Accutane (13-cis RA) and, in cases where the child survives beyond birth, a particular set of behavioural anomalies can be described. Even the adult brain may be susceptible to an imbalance of RA, particularly the hippocampus. This report shows how the properties of RA as a neural induction agent and organizer of segmentation can explain the consequences of RA depletion and overexpression.

Blood and colostrum/milk serum gamma-glutamyltransferase activity as a predictor of passive transfer status in lambs.

The importance of blood and colostrum/milk serum gamma-glutamyl transferase (gamma-GT) enzyme activity was evaluated to assess passive transfer status in healthy lambs. Thirty Akkaraman sheep (3-6 years old) were used which had normal pregnancy period and the same conditions, and the age of the lambs ranged between 0 and 15 days. Blood and colostrum/milk samples were collected from sheep and lambs after birth, before suckling (0) and after on 1st, 3rd, 7th and 15th days. Serum immunoglobulin G (IgG) concentration was determined by the use of Single Radial Immunodiffusion method. Serum gamma-GT activity was measured, using a commercially available kit in blood and colostrum/milk samples. Correlations were carried out between immunoglobulin and gamma-GT levels. Regression models (simple and multiple) were calculated with significant data. Linear correlation was determined between colostrum/milk gamma-GT activity and IgG concentrations and between serum gamma-GT activity and IgG concentrations in lambs on the 0 day. (r: 0.607, P: 0.001), 1st (r: 0.768, P: 0.001) and the 3rd (r: 0.603, P: 0.001) days and on the 1st (r: 0.637, P: 0.001) and 3rd (r: 0.478, P: 0.012) days in the experiment, respectively. Multivariate regression models were developed to estimate sample IgG concentration. Serum and colostrum/milk IgG concentration could be predicted using the formula: lamb serum IgG = 825 + 0.688 (lamb gamma-GT) + 52 (days); colostrum/milk IgG = 832 + 0.505 (colostrum/milk gamma-GT) - 167 (days). The regression models were moderately accurate in predicting serum IgG concentration (R2 = 0.51) and colostrum/milk IgG concentration (R2 = 0.55). Test sensitivity and positive predictive values for serum gamma-GT enzyme activity were found to be 96 and 100% and for colostrum/milk gamma-GT enzyme activity were found to be 100 and 68% to prediction IgG concentration. Serum and colostrum/milk gamma-GT activity can be used to assess passive transfer status of lambs. Along with this, regression models used to calculate serum and colostrum/milk gamma-GT activities found to be useful to estimate sample IgG concentration. The use of serum and colostrum/milk gamma-GT enzyme activity was found useful especially after birth on the 0, 1st and 3rd days.

A role for retinoic acid in regulating the regeneration of deer antlers.

Deer antlers are the only mammalian organs that can be repeatedly regenerated; each year, these complex structures are shed and then regrow to be used for display and fighting. To date, the molecular mechanisms controlling antler regeneration are not well understood. Vitamin A and its derivatives, retinoic acids, play important roles in embryonic skeletal development. Here, we provide several lines of evidence consistent with retinoids playing a functional role in controlling cellular differentiation during bone formation in the regenerating antler. Three receptors (alpha, beta, gamma) for both the retinoic acid receptor (RAR) and retinoid X receptor (RXR) families show distinct patterns of expression in the growing antler tip, the site of endochondral ossification. RAR alpha and RXR beta are expressed in skin ("velvet") and the underlying perichondrium. In cartilage, which is vascularised, RXR beta is specifically expressed in chondrocytes, which express type II collagen, and RAR alpha in perivascular cells, which also express type I collagen, a marker of the osteoblast phenotype. High-performance liquid chromatography analysis shows significant amounts of Vitamin A (retinol) in antler tissues at all stages of differentiation. The metabolites all-trans-RA and 4-oxo-RA are found in skin, perichondrium, cartilage, bone, and periosteum. The RXR ligand, 9-cis-RA, is found in perichondrium, mineralised cartilage, and bone. To further define sites of RA synthesis in antler, we immunolocalised retinaldehyde dehydrogenase type 2 (RALDH-2), a major retinoic acid-generating enzyme. RALDH-2 is expressed in the skin and perichondrium and in perivascular cells in cartilage, although chondroprogenitors and chondrocytes express very low levels. At sites of bone formation, differentiated osteoblasts which express the bone-specific protein osteocalcin express high levels of RALDH2. The effect of RA on antler cell differentiation was studied in vitro; all-trans-RA inhibits expression of the chondrocyte phenotype, an effect that is blocked by addition of the RAR antagonist Ro41-5253. In monolayer cultures of mesenchymal progenitor cells, all-trans-RA increases the expression of alkaline phosphatase, a marker of the osteoblastic phenotype. In summary, this study has shown that antler tissues contain endogenous retinoids, including 9-cis RA, and the enzyme RALDH2 that generates RA. Sites of RA synthesis in antler correspond closely with the localisation of cells which express receptors for these ligands and which respond to the effects of RA.

Clinical efficacy of florfenicol in the treatment of calf respiratory tract infections.

This paper reports on a study of the aetiology of calf pneumonia and the clinical efficacy of florfenicol, a new antibiotic in Turkey. Twenty-seven weaned and unweaned calves (13 males and 14 females) between 1 and 16 months of age brought to the clinics of Selçuk University, Faculty of Veterinary Science. Broncho-alveolar lavage (BAL) fluid samples were taken from the animals diagnosed to have upper respiratory tract infection associated with bronchitis (N=2), bronchitis (N=5), bronchopneumonia (N=4), pneumonia (N=3), pleuropneumonia (N=11), bronchopneumonia plus pulmonary oedema (N=2) based on the results of the clinical and laboratory examinations. Then microbiological isolation and antibiotic culturing were performed. The animals were treated with 1 ml/15 kg (20 mg/kg) florfenicol (Nuflor, DIF) twice within 48 hours via intramuscular injection. At the end of the treatment, 23 of the weaned and unweaned calves were completely healed, 1 calf had died and 3 calves showed no healing. The results of BAL samples and microbiological examinations of the 3 calves that did not respond to the treatment indicated that these cases were affected by mixed infections of yeasts, fungi, and bacteria. Widespread pleuropneumonia was observed. According to the results of the microbiological examination of the BAL samples, Mannheimia (Pasteurella) haemolytica had the highest isolation rate (25%) compared with the other isolated bacteria, namely, Klebsiella pneumonia (20%), Actinomyces pyogenes (15%), beta-hemolytic streptococci. (10%), Staphylococcus spp. (5%), and E. coli (5%). The study also revealed fungi [Penicillum spp. (5%) and Aspergillus spp. (5%)] and two calves (10%) had a yeast infection.. We conclude that florfenicol has a high bacteriological and clinical efficacy (100% and 96% respectively) in the treatment of calf respiratory tract diseases.

Role and distribution of retinoic acid during CNS development.

Retinoic acid (RA), the biologically active derivative of vitamin A, induces a variety of embryonal carcinoma and neuroblastoma cell lines to differentiate into neurons. The molecular events underlying this process are reviewed with a view to determining whether these data can lead to a better understanding of the normal process of neuronal differentiation during development. Several transcription factors, intracellular signaling molecules, cytoplasmic proteins, and extracellular molecules are shown to be necessary and sufficient for RA-induced differentiation. The evidence that RA is an endogenous component of the developing central nervous system (CNS) is then reviewed, data which include high-pressure liquid chromotography (HPLC) measurements, reporter systems and the distribution of the enzymes that synthesize RA. The latter is particularly relevant to whether RA signals in a paracrine fashion on adjacent tissues or whether it acts in an autocrine manner on cells that synthesize it. It seems that a paracrine system may operate to begin early patterning events within the developing CNS from adjacent somites and later within the CNS itself to induce subsets of neurons. The distribution of retinoid-binding proteins, retinoid receptors, and RA-synthesizing enzymes is described as well as the effects of knockouts of these genes. Finally, the effects of a deficiency and an excess of RA on the developing CNS are described from the point of view of patterning the CNS, where it seems that the hindbrain is the most susceptible part of the CNS to altered levels of RA or RA receptors and also from the point of view of neuronal differentiation where, as in the case of embryonal carcinoma (EC) cells, RA promotes neuronal differentiation. The crucial roles played by certain genes, particularly the Hox genes in RA-induced patterning processes, are also emphasized.

The distribution of retinaldehyde dehydrogenase-2 in rat and human orodental tissues.

Retinoic acid is an important signalling molecule in embryological development and continues to be important in the adult animal because it modulates growth and differentiation in many epithelial tissues. The distribution of the enzyme retinaldehyde dehydrogenase-2 (RALDH 2), which is involved in the synthesis of retinoic acid, was studied using immunocytochemical techniques in: (1) the developing orodental region of rats aged between 15 days in utero and 6 months; and (2) in archival human autopsy material consisting of abdominal skin and mucosa from various regions of the mouth. In developing tooth germs, RALDH 2 was absent in the enamel organ and dental papilla, its presence only being noted at the periphery of the dental follicle adjacent to parts of the developing alveolar crypt. In adult teeth, the presence of RALDH 2 was limited to blood vessels in the periodontal ligament. In embryos, the connective tissue beneath the nasal epithelium and the meninges stained strongly positively for RALDH 2, as did the connective tissue beneath nasal epithelium in an adult rat. Both keratinized and non-keratinized human oral epithelia and abdominal skin stained positively for RALDH 2. Staining was present throughout the stratified epithelium, except in the keratinized layer and in the basal layer associated with the dorsal surface of the tongue. In addition, the adnexia as well as the ductal lining of mucous glands stained positively for RALDH 2.