Proliferative vitreoretinopathy — is it anything more than wound healing at the wrong place?

Proliferative vitreoretinopathy (PVR) is a reactive process of the ocular tissue after perforating trauma, retinal detachment, and surgical manipulations. Although several studies, most of them experimental, have focused on the detection of specific etiologic factors in the development of PVR, there is compelling evidence that PVR is nothing more than a physiologic tissue repair process with undesirable consequences for the retina. Important features of PVR involving the role of platelets, mononuclear phagocytes, and fibroblasts parallel the chain of events observed in tissue repair elsewhere in the body. Numerous experimental models for PVR, originally designed to find specific stimuli for the generation of intraocular traction membrane formation, have shown that the process of PVR is the common pathway of the eye's reaction to vitreoretinal trauma of any kind. Accordingly, vitreoretinal surgeons could learn a lot from the work of other disciplines, e.g. surgery and dermatology, on wound healing, and the factors known to modify wound healing elsewhere in the body should be taken into consideration. The well-established impairment of tissue repair processes caused by medical treatment with corticosteroids and cytotoxic agents suggests a combined medical approach to PVR as an adjunct to surgical treatment, using refined methods of application and dosage. Steroids and cytotoxic drugs will influence the course of PVR by suppressing macrophage recruitment and the initial inflammatory reaction as well as the proliferative phase of wound healing with traction retinal detachment, respectively.     

Dental referral of drug addicts

Reasons for drug addicts' non-compliance to dental referral were investigated. Sixty-eight out of 83 addicts referred to the dentist were interviewed. Eighty-one percent intended to go, but only 42% did show up for their first appointment. Mean dental anxiety score (SDAI) was 23.6. An active referral of a non-anxious patient who visited the dentist in the past if in pain appeared least likely to fail. Dental care as an integral part of care for drug addicts is advocated.     

Dynamic interaction between Isp45 and mitochondrial hsp70 in the protein import system of the yeast mitochondrial inner membrane.

The protein import system of the yeast mitochondrial inner membrane includes at least three membrane proteins that presumably form a transmembrane channel as well as several chaperone proteins that mediate the import and refolding of precursor proteins. We show that one of the membrane proteins, Isp45, spans the mitochondrial inner membrane yet is extracted from this membrane at high pH. Solubilization of mitochondria with a nonionic detergent releases Isp45 as a complex with the chaperones mitochondrial hsp70 (mhsp70) and GrpEp. Both chaperones reversibly dissociate from Isp45 upon addition of ATP or adenosine 5'-[gamma-thio]triphosphate, suggesting that dissociation requires the binding of ATP. Control experiments indicate that the interaction between mhsp70 and Isp45 occurs in the intact mitochondria. We propose that Isp45 lines the inside of a proteinaceous channel across the inner membrane and that it is the membrane anchor for an ATP-driven "import motor" composed of mhsp70 and GrpEp. This arrangement is reminiscent of the protein transport systems of the yeast endoplasmic reticulum and the bacterial plasma membrane.     

Sex hormone receptor status of the dental pulp and lesions of pulpal origin

OBJECTIVE: The purpose of this study was to determine whether the dental pulp and lesions of pulpal origin (eg, pulp polyps, periapical granulomas, and periapical cysts) exhibit receptors for the sex steroid hormones estrogen, progesterone, and androgen. STUDY DESIGN: Staining for the receptors of the hormones estrogen, progesterone, and androgen was accomplished through use of available immunohistochemical detection techniques. Pulpal tissues were obtained from freshly extracted human third molars; the other tissues were obtained from the Oral and Maxillofacial Pathology Laboratory archives. Ten samples of each tissue were processed and immunostained for these specific receptors. RESULTS: Staining for estrogen and androgen receptors was essentially negative for all cell populations examined. However, positive progesterone receptor staining of varying degrees was noted in 8 of 10 pulpal specimens. Primarily, pulpal fibroblasts and odontoblasts exhibited positive immunoreactivity. CONCLUSIONS: The results of this study suggest that although the dental pulp may be a potential target tissue for progesterone, evidence is lacking with respect to the other sex steroid hormones.     

Helicobacter pylori products upregulate neutrophil superoxide anion production

Helicobacter pylori-neutrophil interactions may play a pathogenic role in H. pylori-induced gastritis and peptic ulcer disease. To understand these interactions, we explored the effects of H. pylori-derived products on neutrophil chemotaxis and superoxide anion production. H. pylori bacteria were cultured and supernatants fractionated. Neutrophil chemotactic activity was confirmed in the crude supernatants and in one fractionated peak corresponding to a previously described neutrophil chemotactic factor. H. pylori-derived crude supernatant, sonicate and all chromatography-derived peaks failed to directly stimulate neutrophil superoxide anion production. However, after pretreatment with sonicate, neutrophils demonstrated increased superoxide anion production (priming) following subsequent exposure to the secretagogue fmet-leu-phe. These results suggest that H. pylori products may attract neutrophils to the gastric mucosa without initially stimulating superoxide anion production or tissue injury. Oxygen radical-mediated gastric mucosal injury may subsequently result when these primed neutrophils undergo additional stimulation by as yet unidentified factors.     

Caspases as treatment targets in stroke and neurodegenerative diseases

Apoptosis is one of the most exciting and intensely investigated areas of biology and medicine today. Cysteine proteases called caspases serve as the executioners of apoptosis, a form of cell suicide. Hypoxic/ischemic cell death proceeds in part, by apoptosis, particularly within the periinfarct zone or ischemic penumbra. During ischemia, activated caspases dismantle the cell by cleaving multiple substrates including cytoskeletal proteins and enzymes essential for cell repair. Strategies that inhibit caspase activity block cell death in experimental models of mild ischemia, and preserve neurological function. The therapeutic window for caspase inhibition is substantially longer than for glutamate receptor antagonists, and treatment combinations with both classes of drugs decrease ischemic injury and expand the treatment window synergistically. Hence, the caspases are now recognized as novel therapeutic targets for central nervous system diseases in which cell death is prominent. This article will review the evidence and the potential importance of caspase inhibition to cerebral ischemia and briefly summarize an emerging body of data implicating caspases in cell death accompanying neurodegenerative disorders.     

Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway

In view of mounting evidence that the suprachiasmatic nucleus (SCN) is directly involved in the setting of sensitivity of the adrenal cortex to ACTH, the present study investigated possible anatomical and functional connections between SCN and adrenal. Transneuronal virus tracing from the adrenal revealed first order labelling in neurons in the intermedio-lateral column of the spinal cord that were shown to receive an input from oxytocin fibres and subsequently second-order labelling in neurons of the autonomic division of the paraventricular nucleus. The latter neurons were shown to receive an input from vasopressin or vasoactive intestinal peptide (VIP) containing SCN efferents. The true character of this SCN input to second-order neurons was also demonstrated by the fact that third-order labelling was present within the SCN, vasopressin or VIP neurons. The functional presence of the SCN-adrenal connection was demonstrated by a light-induced fast decrease in plasma corticosterone that could not be attributed to a decrease in ACTH. Using intact and SCN-lesioned animals, the immediate decrease in plasma corticosterone was only observed in intact animals and only at the beginning of the dark period. This fast decrease of corticosterone was accompanied by constant basal levels of blood adrenaline and noradrenaline, and is proposed to be due to a direct inhibition of the neuronal output to the adrenal cortex by light-mediated activation of SCN neurons. As a consequence, it is proposed that the SCN utilizes neuronal pathways to spread its time of the day message, not only to the pineal, but also to other organs, including the adrenal, utilizing the autonomic nervous system.     

The economic impact of foot and mouth disease and its control in South-East Asia: a preliminary assessment with special reference to Thailand.

A pilot study of the economic impact of foot and mouth disease (FMD) in the countries and region of South-East Asia is described. Previous economic impact assessments are reviewed and summarised and a synthesis of these contributions is constructed. A framework for the future economic impact of the disease is then developed, incorporating analyses at the sectoral (production system), national and regional levels. Data requirements for such studies are also identified. Integrated epidemiological and economic models for impact assessment were developed and applied to the case study country of Thailand. The models were used to evaluate the economic viability of FMD control programmes in the country. Scenarios evaluated include the effect of improving vaccination coverage and thus reducing productivity losses, and the effect of eventual eradication of the disease. The results indicate that economic returns to the high expenditures incurred in FMD control could be achieved in the short term if greater international trade in pork products was made possible and export prices higher than those in the domestic market could be attained. If FMD were to be eradicated from Thailand in 2010, the eradication would be economically viable, even without exports, with a predicted benefit-cost ratio of 3.73. With additional exports, the economic justification for control becomes much stronger with a benefit-cost ratio of up to 15:1 being achieved. If eradication is not achieved until 2020, returns remain positive without exports, but at a lower rate. The authors propose that the integrated epidemiological and economic models developed be applied to other countries of the region to gain a more accurate insight into the future benefits of FMD control and eradication in the region.     

Diode laser thermokeratoplasty – first clinical experience

Purpose: Pulsed holmium lasers are currently used to correct hyperopia by means of laser thermokeratoplasty (LTK). Series of μs laser pulses are applied with a high repetition rate to induce shrinkage of corneal collagen fibers. The pulsed energy application results in intrastromal temperature peaks of up to 200 °C. A continuously emitting laser diode can – as we demonstrated recently in an invivo study on minipigs – be used for LTK and may be of advantage because the temperature rise is more steady. The aim of this study was to examine the safety, amount, and stability of hyperopic correction of diode LTK on blind human eyes. Methods: We used a laserdiode that was set to continuously emit light at λ = 1.854 μm/μ_a = 1.04 mm^–1(group I, n = 4) or 1.87 μm/μ_a = 1.92 mm^–1 (group II, n = 4). Radiation energy was 100 to 150 mW for 10 s per coagulation. Eight coagulations on a single ring (group I) and 16 coagulations on a double ring (group II) diameter were applied in the cornea concentric to the entrance pupil by means of a vacuum-fixed application mask (group I = conjunctival fixation; group II = corneal fixation) and a handpiece with a focusing optic. Preoperatively as well as 1 week, 1, 2, 3, 6 12 and 18 months postoperative ophthalmologic controls were performed and the corneal refractive power was measured. Results: In group I initial refractive changes of up to + 4.9 D were achieved (1 week postoperative). However, due to the great penetration depth of the laser irradiation, large endothelial defects resulted beneath the stromal coagulations. In group II an initial refractive change of up to + 6.8 D was achieved and as a result of the reduced penetration depth, the endothelial cell damage was much reduced. Partial regression of the refractive effect occured in all subjects, which continued in higher refractive changes during the 2^nd postoperative year. The refractive effect at 12 months was + 0.6 to + 1.5 D in group I and + 0.9 to + 5.7 D in group II. At 12 months the induced astigmatism was 0.5 to 2.2 D in group I and 0.3 to 1.6 D in group II. No serious adverse effects were noticed. Conclusion: A continously emitting laser diode working at a wavelength of 1.87 μm can be used to correct hyperopia by means of LTK safely and effectively. Regression occurs predominantly in the first 6 postoperative months. Further studies must be conducted to determine the importance of patient inherent parameters such as age in establishing a nomogram.