Peripheral eosinophil counts correlate with nasal eosinophil counts in patients with rhinitis

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From modeling to remodeling of upper airways: Centrality of hyaluronan (hyaluronic acid).

After traumatic events (accidental or surgical), the respiratory tract activates specific and prolix repairing mechanisms which tend to claw back the primitive differentiated state. The attempt of reactivation of the normal tissue functions is called 'remodeling' and its aim is to reinstate the modeling mechanisms that existed before the damaging event or the pathology's establishment. Endoscopic sinus surgery represents the gold standard treatment for inflammatory, malformative, benign, and, in selected cases, malignant diseases. The surgical technique is commonly described as minimally invasive as the nostrils are used as an access route and therefore does not leave any external scars. Currently, the surgical procedures, even though minimally invasive regarding the way in, are in fact widely destructive towards the surgical target. The healing process and re-epithelialization will depend on the amount of bony tissue that has been exposed and it will be important to stratify the different surgical typologies in order to foresee the increasing difficulty of mucosal healing process. As far as upper inflammatory diseases are concerned, recent studies demonstrated how intranasal hyaluronic acid can positively regulate mucosal glands secretion and modulate inflammatory response, being a useful tool for the improvement of remodeling after endoscopic sinus surgery. Acid has shown to be able to regulate mucosal glands secretion and modulate the inflammatory response.

Evidence that protease activated receptor 2 expression is enhanced in human coronary atherosclerotic lesions.

AIM: To investigate protease activated receptor 2 (PAR-2) expression in human coronary atherosclerotic lesions because PAR-2 is involved in the modulation of inflammatory events and vascular function. METHODS: An immunohistochemical analysis was performed on serial arterial sections, using the following antibodies: MDA2, a murine monoclonal antibody against malondialdehyde lysine epitopes of oxidised low density lipoprotein (oxLDL); HAM-56, a monoclonal antibody against human macrophages/foam cells; B5, a rabbit polyclonal antibody against PAR-2; and SAM11, a mouse monoclonal antibody against human PAR-2. Sections containing at least one lesion showing substantial immunostaining were counted as positive, and results were expressed as per cent of all sections of the same artery. RESULTS: PAR-2 expression was enhanced in human coronary atherosclerotic lesions. This phenomenon correlated with an increase in oxLDL epitopes in the coronary artery. CONCLUSION: This study shows for the first time that PAR-2 expression is enhanced in human coronary atherosclerotic lesions, and suggests that PAR-2 dependent cellular trafficking may be one of the regulatory signalling responses to vascular injury. Further pharmacological studies will establish whether modulation (and in which direction) of PAR-2 represents a possible therapeutic target for controlling the vascular response to injury.

Microarray analysis: a novel research tool for cardiovascular scientists and physicians.

The massive increase in information on the human DNA sequence and the development of new technologies will have a profound impact on the diagnosis and treatment of cardiovascular diseases. The microarray is a micro-hybridisation based assay. The filter, called microchip or chip, is a special kind of membrane in which are spotted several thousands of oligonucleotides of cDNA fragments coding for known genes or expressed sequence tags. The resulting hybridisation signal on the chip is analysed by a fluorescent scanner and processed with a software package utilising the information on the oligonucleotide or cDNA map of the chip to generate a list of relative gene expression. Microarray technology can be used for many different purposes, most prominently to measure differential gene expression, variations in gene sequence (by analysing the genome of mutant phenotypes), or more recently, the entire binding site for transcription factors. Measurements of gene expression have the advantage of providing all available sequence information for any given experimental design and data interpretation in pursuit of biological understanding. This research tool will contribute to radically changing our understanding of cardiovascular diseases.

Protective role of nuclear factor kappa B against nitric oxide-induced apoptosis in J774 macrophages.

We investigated the role of constitutive transcription factor nuclear factor kappaB (NF-kappaB) in nitric oxide (NO)-mediated apoptosis in J774 macrophages. Our results show that NF-kappaB is present in untreated J774 cells in a form constitutively active. Incubation of cells with sodium nitroprusside (SNP) and S-nitroso-glutathione (GSNO), two NO-generating compounds, caused: (a) inhibition of constitutive NF-kappaB/DNA binding activity; (b) decrease of cell viability; (c) DNA fragmentation; (d) ApopTag positivity. Pyrrolidine dithiocarbamate (PDTC) and N-alpha-para-tosyl-L-lysine chloromethyl ketone (TLCK), two inhibitors of NF-kappaB activation, showed the same effects of both NO-generating compounds. Furthermore, SNP and GSNO as well as PDTC and TLCK significantly increased the cytoplasmic level of IkappaBalpha. All together these results demonstrate that constitutive NF-kappaB protects J774 macrophages from NO-induced apoptosis. Moreover, these findings show, for the first time, that NO-generating compounds may induce apoptosis in J774 macrophages by down-regulating constitutive NF-kappaB/DNA binding activity and suggest a novel mechanism by which NO induces apoptosis.

A standardized procedure for using human corpus cavernosum strips to evaluate drug activity.

The main problem of using human corpus cavernosum (HCC) tissue to perform bioassay is linked to its limited availability further complicated by the heterogeneous source of the tissues used. Here, we show that gender reassignment is a reliable source of human tissue without major ethical problems. Indeed, the entire corpus cavernosum is obtained from the surgery procedure, which allows creating a standardized procedure to prepare HCC strip. In addition, human tissue, if kept in the fridge in the condition described, does not loose its ability to contract to phenylephrine (PE; alpha agonist), angiotensin II (AG II) and KCl up to 4 days. Furthermore, once contracted with PE, HCC relaxes to acetylcholine (endothelium-dependent mechanism); sodium nitroprusside (endothelium-independent mechanism); cromakalim (CRK), a K(ATP) channel opener; or alprostadil, a synthetic PGE2 (ALPR). In conclusion, we have standardized a procedure that allows the use of HCC strips to evaluate drug activity and/or to study pathophysiological mechanisms with an intact functional human tissue up to 4 days from the surgery procedure.

Modulation of cytokine production in activated human monocytes by somatostatin.

The immunosuppressor effects of the widely distributed neuropeptide somatostatin were examined on purified peripheral blood human monocytes. Somatostatin, at concentrations thought to be physiologic (10(-10)-10(-7) M), regulated monocyte/macrophage responses to (LPS) stimulation, as reflected by interleukin production. In particular, somatostatin had direct inhibitory effects on TNF-alpha, IL-1 beta, and IL-6 secretion by LPS-activated monocytes, while the decrease on IL-8 synthesis was modulated mainly by the action of somatostatin on TNF-alpha and IL-1 beta. In fact, the addition of these two inflammatory cytokines to the monocyte culture medium was able to induce IL-8 expression, as demonstrated by mRNA analysis, also in presence of the neuropeptide. Although somatostatin affected IL-8 production in an indirect way, it suppressed directly the chemotactic response of neutrophils to IL-8. Finally, somatostatin downregulation of monocyte activation was confirmed by the decrease of HLA-DR expression on cell plasma membranes (52% versus 33%). Our results confirm that somatostatin exerts preferential effects on the suppression of immunoreactions by modulating cytokine production and activity.

Is there a correlation between osteoclastic activity and the action of calcitonin on macrophagic activity?

The formation of granulomas from a foreign body was studied by means of the subcutaneous implantation of cotton fragments in rats treated with salmon calcitonin or with just the diluent. The formation of granulomas was evaluated in optical microscopy, transmission and scanning electron microscopy (TEM and SEM, respectively). The cellular populations of the granuloma were immunophenotyped and flow analyzed in cytofluorometry (FACS = fluorescence-activated cell sorter). In the group treated with calcitonin, a lesser inflammatory effect of the cotton fragments was found compared to the group treated with only the diluent. These results indicate that, in addition to inhibiting bone resorption, salmon calcitonin has several important anti-inflammatory effects.

Mandibular lengthening by external distraction: an experimental study in the rabbit.

OBJECTIVE: To observe the development of bone at different times during the period of mandibular lengthening by external distraction using Ilizarov's transosseous osteosynthesis technique. MATERIALS AND METHODS: Fifteen rabbits, 2 to 3 kg in weight, were used for this experiment. The left side of the mandible was exposed and a corticotomy was performed with a water-cooled drill. After 12 hours, distraction was started and continued 1 mm per day for 2 weeks. Plain radiography and three-phase bone scan scintigraphy were performed on the 1st, 7th, and 14th postoperative days. The mandibles were then either removed for immediate histologic evaluation or after 2, 5, or 8 weeks of postdistraction fixation. RESULTS: Elongation of up to 11 mm was achieved. Radiographic and scintigraphic evaluation suggested a residual inflammation on the 7th day and definite ossification on the 14th day. Histologic observations of the distraction site showed a gradual change from an amorphous matrix to a fibrous matrix and, finally, an osseous-like tissue. CONCLUSION: Bone lengthening by gradual distraction is commonly used in tubular bones. To achieve mandibular lengthening it is necessary to resolve many problems. Morphologic, radiographic, scintigraphic, and histologic observations confirm that mandibular lengthening by external distraction is possible, with the formation of new bone tissue.

Macrophage activation induced by different carbon fiber-epoxy resin composites.

The activation of cells by interaction with solid surfaces is important in many settings, including the response of tissue to implanted materials. However, few comprehensive studies of both cell migration and activation have been performed so that the connection between these events and immunological activation against foreign material is not well understood. In the present study, synthesis and expression of Ia antigens by peritoneal exudate macrophages after implantation of different carbon fiber composites in the rat peritoneal cavity have been investigated in order to determine whether the type of material implanted affected the composition of Ia-bearing cells of the exudate. The results have confirmed the low level of expression of Ia on resident peritoneal macrophages; while we have found that macrophages, harvested after implantation, express a different amount of Ia related to the different cure cycles of the composite material used.

Rat peritoneal immune response to carbon fibre reinforced epoxy composite implants.

The aim of this paper was to evaluate the histocompatibility of differently cured carbon fibre reinforced epoxy composites, studying their potential to induce an intolerance reaction in neighbouring tissues after peritoneal implantation in the rat. According to the microscopic and scanning electron microscope findings, the inductive capacity to generate connective tissue and cellular reaction was greatest in the partially cured material compared to the fully cured material. In addition, only the partially cured material implants appeared totally coated by macrophages at various stages of activation. The differences in the cellular reactions and scar tissue deposition in the interstices of these two composites are probably related to the chemical surface properties rather than to the structural characteristics of the materials.

The structure and development of osteogenetic repair tissue according to Ilizarov Technique in man. Characterization of extracellular matrix.

Distraction osteogenesis by the method of Ilizarov has permitted the study of bone formation. This is an analysis of 64 human biopsies in patients who were undergoing tibial lengthening by the method of Ilizarov. After analysis by conventional and polarized light microscopy, four stages of bone formation were identified. Bone formation is of the direct type with no cartilaginous phase.

A retrovirus carrying the polyomavirus middle T gene induces acute thrombocythemic myeloproliferative disease in mice.

Mice inoculated with an artificially constructed retrovirus carrying the middle T gene of polyomavirus develop acute myeloproliferative disease with severe thrombotic and hemorrhagic disorder and impaired platelet function. The megakaryocytic lineage appears to be a target for polyoma-murine leukemia virus infection and middle T gene expression. This newly described disease represents a unique model system for studying disorders of the megakaryocytic lineage.

Synthesis of seminal ribonuclease in isolated lobules of bull seminal vesicles.

A procedure is described for preparing and maintaining in culture isolated lobules of bovine seminal vesicles, consisting of glandular acini, surrounded by little connective tissue and with free access to the external medium, in which secreted material can be collected. After 48 h in culture, the isolated lobules appeared indistinguishable, by morphological and biochemical criteria, from freshly isolated lobules. After much longer culture times about one third of the glandular cells were still capable of effective protein synthesis. Studying the biosynthesis of seminal ribonuclease with preparations of isolated lobules we found that the enzyme was synthesized and secreted; only the fully amidated isoenzyme was synthesized and secreted, indicating that production of the selectively deamidated isoenzymic forms occurred after secretion, newly synthesized protein was rapidly exported, indicating that the high levels of enzyme previously reported for the seminal vesicle tissue were essentially due to its content of stored secretion.

[End-to-side anastomosis made with a short circulatory interruption in the receiving vessel. Experimental model in the rat]. / Anastomose termino-latérale réalisée avec une brève interruption circulatoire du vaisseau receveur. Modèle expérimental chez le rat.

End to side microsurgical anastomoses between vessels of small calibre require interruption of blood flow of about 25-40 min. In terminal vascular beds this time may be incompatible with the cellular survival. The authors refer their experience in rats with a partly original experimental technique requiring less time of clamping the receiving vessel (about 3-4 min), as the main part of the anastomosis is performed between the wall of the donor vessel and the adventitia of the receiving vessel, without interruption of blood flow in this latter. Histological examinations, performed 21 days later, reveal a patency rate of 60%.

Transglutaminase-mediated modifications of the rat sperm surface in vitro.

Two transglutaminase-mediated modifications of the rat epididymal spermatozoon surface were demonstrated in vitro. Transglutaminase was effective in promoting the binding of spermidine to the sperm. Moreover, the enzyme, by reacting with one of the major proteins secreted by the rat seminal vesicle epithelium, produced a modified form of the protein with a higher molecular weight and the capability of binding to the sperm cells. A specific physiological role for the enzyme, bringing about modifications of the rat sperm surface in the seminal fluid environment, is suggested.

Location of 64K collagen producer chondrocytes in developing chicken embryo tibiae.

The synthesis of a new low-molecular-weight collagen by cultured chicken embryo chondrocytes has been recently demonstrated (Capasso et al., Exp. Cell Res. 142:197-206, 1982; Gibson et al., J. Cell Biol. 93:767-774, 1982; Schmid and Conrad, J. Biol. Chem. 257:12444-12450, 1982). In this paper we report results on the location of chondrocytes synthesizing this new collagen (64K collagen) in the developing chicken embryo. The 64K collagen is synthesized in very large amounts by cells concentrated at the diaphysis of 9-day-old and at the epiphysis of 17-day-old embryo tibiae. These regions are characterized by a remodeling of the cartilage matrix leading to the replacement of the cartilage with bone tissue; therefore, this collagen appears to be a marker of a specific developmental stage of chondrocytes. The origin of cells competent for the synthesis of the 64K collagen is also discussed.