Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

Abdominal wall reconstruction after open management of the septic abdomen

The increasing popularity of open management of the septic abdomen has generated a challenge that the surgeon is forced to face more frequently. The typical presentation is that of a patient with a full-thickness abdominal wall defect occurring after a protracted, severe illness. The various methods of reconstruction of the abdominal wall are reviewed and evaluated. The reconstruction should only be attempted once intra-abdominal sepsis is controlled, re-exploration of the peritoneal cavity is no longer necessary and organ support is discontinued. Although various methods of reconstruction are described, the recommended technique consists of either medial advancement of the rectus abdominis muscle or direct application of split-thickness skin grafts. Mid-line abdominal defects may also be repaired with tensor fasciae latae or rectus femoris flaps.     

Nitric oxide synthase inhibitor,nitro-iminoethyl-L-ornithine,reduces ischemia-reperfusion injury in rabbit skeletal muscle

Nitric oxide (NO), originally identified as the mediator of endothelial-dependent relaxation of vascular smooth muscle, is now known to also have cytotoxic effects under certain conditions. Thus, we have investigated the effects of inhibition of NO synthesis on ischemia/reperfusion injury in the rabbit rectus femoris muscle. Three and a half hours of ischemia and 24 hours of reperfusion resulted in a 56% loss of viability. In muscles receiving an infusion of the nitric oxide synthase inhibitor, L-NIO (30 μM), the loss of viability was reduced to 15%. Post-ischemic blood flow was increased in muscles receiving a saline infusion, whereas there was a marked decrease in blood flow for at least the first 60 minutes of reperfusion in muscles treated with L-NIO (30 μM). The increase in myeloperoxidase levels (indicative of neutrophil accumulation) following 24 hours of reperfusion was attenuated with L-NIO infusion by approximately 50% and the reperfusion-induced edema was also attenuated in L-NIO treated muscle. These findings suggest that endogenous NO production during ischemia/reperfusion injury may be deleterious to muscle survival. © 1994 Wiley-Liss, Inc.     

Central nervous system and cardiac manifestations of hydrochlorothiazide overdosage; treatment with hemodialysis

A patient with end-stage renal failure inadvertently received high-dose hydrochlorothiazide as treatment for hypertension, resulting in CNS and cardiac toxicity. These toxic manifestations were successfully treated with hemodialysis. A hydrochlorothiazide dialysance of 62.5 mL/min was demonstrated. The possibility of hydrochlorothiazide toxicity should be considered in any patient with renal insufficiency who exhibits unexplained arrhythmias or symptoms related to the CNS.     

Comparative distribution and excretion of carboplatin and cisplatin in mice

Summary The comparative distribution and excretion of Carboplatin (cis-diammine-1,1-cyclobutane dicarboxylate platinum II, CBDCA, JM8) and cisplatin have been investigated in Balb C^- mice following i.v. administration of the maximally tolerated doses (MTDs) of the compounds. Although the concentrations of platinum in the plasma and tissues during the -phase were much higher for Carboplatin than for cisplatin, reflecting the difference in the doses used (4 vs 80 mg/kg), the tissue-to-plasma ratios were similar. During the -phase (1–10 days), however, both the platinum concentrations and the ratios were found to be similar for most tissues when cisplatin and Carboplatin were compared. The platinum concentrations and the tissue-to-plasma ratios of the spleen, brain, muscle, testes, ovary and bile, on the other hand, were consistently higher (two- to sixfold) after Carboplatin than after cisplatin. The highest ratios (>20) were found in the kidney, liver, spleen (after Carboplatin only) and skin at 6 days after treatment. Comparison of the two compounds showed that the half-lives of platinum in the plasma and tissues during both the - and -phases were similar, except for the spleen, in which a nine-fold greater t 1/2 was recorded for Carboplatin than for cisplatin. The main route of excretion for the two complexes is via the kidneys, with 52% of cisplatin and 93% of Carboplatin being excreted during the first 3 days. The major part of this, however, is excreted within the 1st day. These results indicate that, although there are quantitative differences, the distribution and excretion profiles are similar for Carboplatin and cisplatin.     

Effect of biomaterial properties on bone healing in a rabbit tooth extraction socket model

In this work we sought to understand the effect of biomaterial properties upon healing bone tissue. We hypothesized that a hydrophilic polymer gel implanted into a bone tissue defect would impede the healing process owing to the biomaterial's prevention of protein adsorption and thus cell adhesion. To test this hypothesis, healing bone was investigated within a rabbit incisor extraction socket, a subcritical size bone defect that resists significant soft tissue invasion by virtue of its conformity. After removal of the incisor teeth, one tooth socket was left as an empty control, one was filled with crosslinked polymer networks formed from the hydrophobic polymer poly(propylene fumarate) (PPF), and one was filled with a hydrogel formed from the hydrophilic oligomer oligo(poly(ethylene glycol) fumarate) (OPF). At five different times (4 days as well as 1, 2, 4, and 8 weeks), jaw bone specimens containing the tooth sockets were removed. We analyzed bone healing by histomorphometrical analysis of hematoxylin and eosin stained sections as well as immunohistochemically stained sections. The proposed hypothesis, that a hydrophilic material would hinder bone healing, was supported by the histomorphometrical results. In addition, the immunohistochemical results reflect molecular signaling indicative of the early invasion of platelets, the vascularization of wound-healing tissue, the differentiation of migrating progenitor cells, and the formation and remodeling of bone tissue. Finally, the results emphasize the need to consider biomaterial properties and their differing effects upon endogenous growth factors, and thus bone healing, during the development of tissue engineering devices.     

Rules for the classification of younger children with nonverbal learning disabilities and basic phonological processing disabilities.

Rules for the classification of Nonverbal Learning Disabilities (NLD) and Basic Phonological Processing Disabilities (BPPD) that had been generated and tested on older children (ages 9-15) were applied to younger children (ages 7-8). The goal was to evaluate the applicability of these classification rules for a younger population with NLD and BPPD, and to make revisions if necessary. These rules were used to differentiate these two subtypes of learning disabilities using levels and patterns of performance on motor/psychomotor, tactile/perceptual, visual-spatial, auditory-perceptual, problem solving, and language measures. An experienced child-clinical neuropsychologist classified each child. Only those children who received a classification of NLD or BPPD by the neuropsychologist and those who met criteria for definite or probable NLD and BPPD as defined by the rules were used in this study. Revisions were made to these rules for younger children. Revised rules allow for their use as a source of information to assist a clinician in deciding whether a comprehensive neuropsychological evaluation would be valuable. They may also be useful for research purposes.