ABSTRACT Microstructural and biomolecular preservation is reported in fossils as old as the Triassic. Such preservation suggests unusual taphonomic conditions. We collected fragments of fossil whale bone from silty, tuffaceous, and diatomaceous rocks of the middle-upper Miocene portion of the Pisco Formation. The whale fossils within the region are generally well-preserved and mostly articulated, including some specimens with in situ baleen. Due to the depositional setting associated with the preservation of these fossils, they could be expected to be favorable candidates for the preservation of cellular microstructures and/or original biomolecules. To test this hypothesis, fossil whale bone fragments were subjected to microscopic analysis and EDTA-mediated demineralization to release extractable materials. Microscopy of partially demineralized fossil bones revealed quartz-permineralized osteocyte-like and vessel-like structures. Protein assay (micro-Bicinchoninic Acid Assay) of the supernatants obtained from demineralized fossils yielded 12 to 19.5 μg of protein per gram of bone. MALDI-TOF analysis of the extracted protein demonstrated the presence of approximately 5 kD molecules in one fossil sample, consistent with the presence of highly fragmented polypeptides. An LC-MS/MS analysis of the fragmentation pattern of the tryptic digest of extracted protein was performed. However, attempted protein identification was unsuccessful. Nevertheless, this study first documents the microstructural preservation with some silicification of the fossil whale bones of the Pisco Formation, and then quantifies extractable protein from these bones. It adds to the growing body of reports of microstructural and organic preservation in fossils.

INTRODUCTION:Traditional pulp regeneration procedures that use a blood clot as a scaffold have produced histologic evidence of bone, cementum, and connective tissue growth within the root. Platelet-rich plasma (PRP) is a bioactive scaffold containing growth factors that enhance wound healing.AIM:The aim of this study was to histologically compare the tissues generated when PRP or a blood clot is placed into teeth with preexisting necrotic pulps and periapical lesions.METHODS:Twenty-four canine teeth from 6 immature ferrets were used. Two ferrets served as positive controls. Sixteen experimental canine teeth from 4 ferrets were infected, debrided, treated with a triple antibiotic paste, and randomly distributed to the following groups: group 1 (blood clot/Gelfoam), group 2 (PRP), and group 3 (no scaffold). At 3 months, the ferrets were sacrificed, and the tissues were evaluated histologically. Data were analyzed by using the Fisher exact test (P < .05).RESULTS:In 3 of 6 teeth in the PRP group, 2 of 6 teeth in the blood clot group, and 1 of 4 teeth in the no scaffold group, an ingrowth of hard tissues was observed in the apical third of the roots. When using PRP or a blood clot as a scaffold, we found significantly more apical narrowing and hard tissue deposition in comparison to not using a scaffold (P < .05).CONCLUSIONS:The use of PRP or blood clots as scaffolds results in the ingrowth of bone-like, cementum-like, and connective tissue in the apical third of the roots at inconsistent rates.

INTRODUCTION:A growing body of evidence is demonstrating the possibility for regeneration of tissues within the pulp space and continued root development in teeth with necrotic pulps and open apices. There are areas of research related to regenerative endodontics that need to be investigated in an animal model. The purpose of this study was to investigate ferret cuspid teeth as a model to investigate factors involved in regenerative endodontics. METHODS:Six young male ferrets between the ages of 36-133 days were used in this investigation. Each animal was anesthetized and perfused with 10% buffered formalin. Block sections including the mandibular and maxillary cuspid teeth and their surrounding periapical tissues were obtained, radiographed, decalcified, sectioned, and stained with hematoxylin-eosin to determine various stages of apical closure in these teeth. RESULTS:The permanent mandibular and maxillary cuspid teeth with open apices erupted approximately 50 days after birth. Initial signs of closure of the apical foramen in these teeth were observed between 90-110 days. Complete apical closure was observed in the cuspid teeth when the animals were 133 days old. CONCLUSIONS:Based on the experiment, ferret cuspid teeth can be used to investigate various factors involved in regenerative endodontics that cannot be tested in human subjects. The most appropriate time to conduct the experiments would be when the ferrets are between the ages of 50 and 90 days.

Rediscovering psychoanalysis. Thinking and dreaming, learning and forgetting, by Thomas Ogden, London, Routledge, 2009, 168 pp., £22.99 (paperback) Over the last 30 years, the American psychoanalys...

Medical researchers exercise and delegate agency for making inferences or for making claims. In the biostatistical consultations discussed here, they encounter three key knowledge-producing agents in the "epistemic culture" (Knorr Cetina, 1999) of biostatistics: themselves, biostatistician and computer machinery. Who or what does what occurs amidst a "dance of agency" among the participants (Pickering, 1995). These interpretations provide support for recent reforms employing modeling approaches in science and mathematics instruction in K-16 settings.

This paper explores how we sometimes manage, and often fail, to communicate the 'feel' of live experience. Since poetry makes a craft and vocation of this pursuit, the writings of poets are brought to bear on the process. I introduce the idea of containing forms, using the term containment in its everyday sense. My argument, however, owes much to Winnicott, Stern and Bion, Winnicott's transitional object exemplifying an early containing structure, and Stern's 'attunement' suggesting ways that later containing structures might arise out of mother-infant dialogue. Bion's more specific notions of containment and transformation are not explored. Following Langer, I suggest that feeling is better communicated through presentational rather than discursive symbols, such forms being concrete, sensory, and isomorphic in some way to that which is being shared. With such presentational symbols, resonance and dialogue between forms are more important than explanatory meaning and some implications of this for therapeutic discourse are discussed.

The purpose of this study was to identify the hard tissue formed early in experimental pulp exposures capped with mineral trioxide aggregate (MTA) or bone morphogenetic protein (BMP)-7 using dentin sialoprotein (DSP) as a marker. The pulps of 35 maxillary first, second, and third molar teeth from 10 male rats were experimentally exposed. The pulps were capped with MTA alone as a pulp-capping agent and final restoration or with BMP-7 followed by restoration with MTA. Five teeth with class I occlusal preparations, no exposure, and no restoration served as positive controls. Five teeth that received pulp exposures and no restoration served as negative controls. Five untreated third molars served as additional controls. The animals were killed at 2 weeks. The specimens were prepared and evaluated histologically and with immunohistochemistry using polyclonal antibodies raised against rat DSP. Pulps capped with MTA formed hard tissue that demonstrated significantly more immunostaining for DSP compared with BMP-7 (p = 0.0031). MTA-capped pulps also showed significantly more complete bridge formation compared with BMP-7 (p = 0.0008). Pulps capped with BMP-7 demonstrated a hard tissue that was bone-like in appearance and devoid of DSP staining.

Purpose: The present study addresses the natural history ocular alignment in infantile esotropia that presents at 2 to 4 months of age. Methods: Eye alignment during the first 6 months of life was evaluated in two cohorts of healthy infants who initially had esotropia at 2 to 4 months of age; 80 infants were enrolled in a prospective study at the Retina Foundation of the Southwest (RFSW), and 41 infants were reviewed retrospectively as a pilot study for the Early Surgery for Congenital Esotropia (ESCET) multicenter trial. In addition, 79 of the 80 children in the RFSW cohort were reexamined at 4.5 years of age or older for ocular alignment and stereopsis. Results: Among infants who initially had constant esotropia ≥40 PD, 0 of 45 children in the RFSW cohort and 0 of 21 children in the ESCET cohort showed resolution to orthophoria. In addition, only 2 infants showed a reduction in angle of deviation below 40 PD (one to 35 PD and one to 20 PD). Resolution to orthophoria was noted in a few infants who initially had small angle or variable angle esotropia. On follow-up at 4.5 years of age or greater, 91% of the children in the RFSW cohort had alignment within 8 PD of orthoposition and 30% had stereoacuity of 3000″ to 60″. Children who underwent surgical alignment at 6 months of age had a higher prevalence of coarse stereopsis than children who underwent alignment at 7 to 15 months of age. Conclusions: Taken together, these results suggest that infants who present at 2 to 4 months of age with constant esotropia of 40 PD or greater are valid candidates for surgical treatment. In addition, data from long-term follow-up support the hypothesis that early surgical alignment may promote the development of at least coarse stereopsis in these infants.

Rationale and Objectives. The authors' purpose was to define the stability and drug-carrying and drug-releasing capacity of ethiodized oil emulsions in the hepatic circulation.Methods. Emulsions prepared in various ratios of a nonionic contrast material containing doxorubicin to ethiodized oil were injected into the hepatic arteries of normal and tumor-bearing livers in rats or mice. In vivo microscopy was used to observe the dynamic distribution of the emulsions in the hepatic circulation.Results. A solution of less water mixed with more oil formed water-in-oil (w/o) phase emulsions, whereas less oil with more water formed oil-in-water (o/w) emulsions. The oil in the emulsions carried the water in the blood circulation. The w/o emulsions exhibited significantly higher carriage capacity and longer release time for the drug solution than did the o/w emulsions (P < .01).Conclusion. The delivery capacity of w/o emulsions is superior to that of o/w emulsions. Further studies about preparation methods and delivery capability of emulsions in the liver are warranted.

The simultaneous exposure of a biological system to a mixture of toxic substances may result in an ideal or nonideal combination of effects. In an extension of linear isobole theory, models are quantitatively developed to describe these combinations, in which the nature of the nonideal effect combination may or may not be a function of the magnitude of predicted response (as opposed to only the proportions of the substances in a mixture). The approach is tested using data on rat carcinogenesis, drug action, and aquatic toxicity of pesticides. In the cases examined, the models predict substantial deviation from ideal behavior even under low doses.

The use of natural products as a source of new agrochemicals and the procedures that can be undertaken to discover such compounds are reviewed using examples from both the literature and our own experiences. The commercial successes obtained to date show that natural products are a powerful source of new agrochemicals. The results from a survey of the views of the agrochemical industry of natural product work indicated a high level of interest, with 16 of the 19 companies that replied being involved in natural product work either through in-house or external programmes of work. Possible approaches to the key challenges of natural product work, for example choice of sources and screens, avoiding known metabolites and obtaining sufficient compound for biological evaluation, are discussed.

Three phosphinate salts (5), (6) and (7) were prepared as potential inhibitors of the enzyme pantothenate synthetase. The synthesis of compound (5) utilises a (diethoxymethyl)-protected phosphinate (8) as a new reagent for the formation of unsymmetrical phosphinic acids and esters. Initial P-alkylation of (8) followed by a selective deprotection sequence yields intermediate P-H phosphinates (16) and (21) which can be P-alkylated a second time. Enzyme assays have been performed with the target compound and the results are discussed.

Hepatic metastases rather than the primary neoplasm usually dictate the course of the disease and the patient's survival. For unresectable disease, intraarterial infusion of chemotherapy, embolization, and chemoembolization are viable alternatives. Intraarterial therapy for hepatic metastases is based on the dual blood supply of the normal liver (portal vein, 75%, and hepatic artery, 25%) and that of the tumors (hepatic artery, 90%). Intraarterial infusion delivers a higher concentration of chemotherapy, whereas chemoembolization adds ischemia and increased contact time with the tumor. Selective vascular occlusion for infusion, redistribution of the blood supply and pulsatile flow enhance the delivery of therapeutic agents to the liver.

Pyruvate dehydrogenase is already well known as a site of action of pesticides, although the compounds that act there are either nonspecific or rather weak inhibitors. In the present study a series of acyl phosphinates has been prepared as potential mechanism-based inhibitors of the enzyme. Some of these are very powerful inhibitors and are also herbicidal, and a substantial body of evidence is presented to support the view that susceptible plants die as a direct result of the enzyme inhibition. Further synthesis has led to the discovery that certain derivatives of the inhibitors (which are presumably converted to the parent phosphinate in vivo) are also good herbicides, and one of these (an acetal) has been extensively evaluated in the field. Although this compound appeared to have insufficient commercial potential, the results of the study encourage the view that biochemical design of agrochemicals will be successful.

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In an attempt to avoid toxic reactions of the eye as a complication of internal carotid arterial infusion of cisplatin, carmustine, or a combination of both for the treatment of brain tumors, a new Gore-Tex/Teflon coaxial catheter system has been used for supraclinoid placement. Catheter placement was successful in 14 of 16 attempts in eight patients. Two patients experienced eye pain and conjunctivitis--a result of the chemotherapeutic agent leaking through the Gore-Tex portion of the catheter at the infusion rate of 170 ml/h. No complications were noted as long as the infusion rate was maintained at 125 ml/h or lower.