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The importance of atmospheric odors for homing pigeon navigation was tested using birds from a loft located in Savannah, GA, in the southeastern United States. When released from a familiar training site, control pigeons and pigeons given intranasal injections of zinc sulfate to produce anosmia both displayed good homeward orientation and homed quickly. When released from three unfamiliar release sites, in contrast, control birds tended to orient southeast, while zinc sulfate-treated birds were more likely to fly northwest. More importantly, while the majority of control pigeons returned to the home loft, few of the zinc sulfate-treated birds returned. The good performance of both groups from the familiar site indicates that zinc sulfate treatment does not impair the general motor ability or motivation of homing pigeons. Therefore, the observed impairment in homing success of the zinc sulfate-treated pigeons from the unfamiliar locations presumably reflects an impaired ability to use atmospheric odors to navigate home. As such, the data support the hypothesis that successful homing pigeon navigation is based on the perception of atmospheric odors and that olfactory navigation is the primary mechanism used by pigeons over a broad range of geographic areas to approximate their relative position with respect to home from unfamiliar locations.

Besides functional estrogen receptors, the presence of signalling cell surface binding sites for 17beta-estradiol (17betaE2) has been reported in osteoblast- and osteoclast-like cells, suggesting that 17betaE2 may influence bone remodelling by a dual mechanism of action: to affect gene expression mediated by the nuclear activity of the steroid-receptor complex, and to initiate rapid responses triggered by a signal-generating receptor on the cell surface. Recently, we demonstrated that the human pre-osteoclastic cell line FLG 29.1 bears functional estrogen receptors. In this study we examined FLG 29.1 cells for the presence of cell surface binding sites for 17betaE2, and whether 17betaE2 could elicit cell signalling. Using a cell-impermeant and fluorescent estrogen conjugate, 17beta-estradiol-6-carboxymethyloxime-bovine serum albumin-fluorescein isothiocyanate, we demonstrated the presence of specific plasma membrane binding sites for 17betaE2. Stimulation of FLG 29.1 cells with low (1 nM) and high (1 microM) doses of 17betaE2 induced a prompt and significant (P < 0.05) increase of cellular pH, as measured in single cells using an image analysis system. In addition, both cAMP and cGMP were significantly increased by 17betaE2 with a dose-dependent response. Finally, a rapid increase of intracellular calcium ion concentration [Ca2+] was also induced by 1 nM 17betaE2, as measured in single cells using an image analysis system. Our findings strongly suggest a non-genomic action of 17betaE2 on osteoclast precursors.

The aims of medical therapy in chronic pancreatitis are mainly to relieve the recurrent pain and to correct any malabsorption secondary to digestive insufficiency resulting from deficient exocrine pancreatic function. The treatment of the pain initially involves the use of dietary measures and analgesic drugs. The results of the use of pancreatic extracts and somatostatin reported in the literature are controversial, as are those of coeliac plexus block. Of unquestionable efficacy, at least in the short to medium term, are surgical decompression interventions in patients, with pain refractory to these measures and who present significant dilation of Wirsung's duct at ERCP. Endoscopic decompression constitutes an alternative to surgical decompression. In view of the transitory results of endoscopic decompression, which, in any event, should be implemented only by endoscopists possessing the necessary experience and expertise, the use of this technique may perhaps be targeted at carefully selected patients to be submitted to surgical decompression. As far as maldigestion is concerned, which occurs only when the pancreatic functional deficit reaches 90% or more, replacement therapy with pancreatic extracts must be resorted to. Multi-Unit Dose preparations are to be preferred, consisting in gastro-protected microspheres measuring not more than 2 mm in diameter and containing high doses of lipase, since at least 30,000 I.U. of lipase are required in the post-prandial phase for reasonably satisfactory correction of the steatorrhoea. Should this fail to prove effective, it is good policy to add antisecretory drugs (H2-antagonists, proton-pump inhibitors).

Non-organic dyspepsia, although not frequently reported, is still a disorder which is difficult to classify in nosographic and physiopathological terms, a fact which inevitably influences the indications for its treatment. Non-pharmacological treatment of non-organic dyspepsia includes changes in dietary and behavioural habits which, even if established on empirical grounds, play a far from ancillary role. When considered appropriate, pharmacological treatment must be formulated solely on the basis of controlled clinical trials vs placebo given the well-known significance of the placebo effect in this and other so-called "functional" diseases. The therapeutic strategies which are most subject to verification are based on the one hand on the neutralisation or inhibition of gastric acid secretion and, on the other, on the improvement of gastrointestinal motility. Surprisingly, the widely used antacid drugs are among those which have been less well studied and show the lowest efficacy. Among the anti-secretory drugs, pirenzepine is approximately 25% more effective than placebo. H2-antagonists, the drugs which have been most closely studied both in terms of the number of trials and the size of the sample populations studied, produce contradictory results. However, a meta-analysis of the trials shows an overall 18% improvement in efficacy compared to placebo. The overall results of studies on prokinetic compounds are "good" in meta-analytical terms, with an improved efficacy of 50% compared to placebo. This is not necessarily due to the superiority of prokinetic compared to anti-secretory drugs and can be explained by the reduced placebo effect in trials using prokinetic drugs or a greater presence in the latter of dyspepsia which is physiopathologically correlated to motor discord. Among the future drugs still being studied, it is particularly worth mentioning fedotozine, a specific K opioid receptor agonist which appears to have provided extremely interesting results in preliminary studies. The role of barrier drugs, such as sucralfate and colloidal bismuth, continues to remain unclear and in particular the latter might be of increased use if evidence of a relationship between Helicobacter pylori and non-organic dyspepsia were reinforced; this relationship may in fact not exist in all dyspeptic patients but only in a subgroup. Lastly, the problem of the duration of pharmacological treatment still remains unsolved, as do the questions of whether longterm treatment should be conceived once acute symptoms have disappeared and whether it is possible to hypothesise differentiated pharmacological treatment depending on the clinical variants of functional dyspepsia which have been defined with greater attention over the course of the past decade.

Using a clonal line of bovine parathyroid endothelial cells (BPE-1) we defined the presence on these cells of a histamine H2 receptor and characterized its pharmacological properties. Interaction of histamine with its receptor induced an increase of cAMP accumulation in a dose- and time-dependent fashion. This effect appears unique for parathyroid endothelial cells, in fact, clonal parathyroid epithelial cells did not exhibit a similar response. No effect of histamine was observed on BPE-1 cell proliferation.

Using a coculture system, we have recently demonstrated that insulin-like growth factor I (IGF-I) is a mediator of preosteoclastic cell migration toward bone-derived endothelial cells. To better characterize the mechanisms of IGF-I action on preosteoclastic cells we evaluated the expression of type I IGFs receptor in the human leukemic cell line, FLG 29.1, which differentiates toward the osteoclastic phenotype following phorbol ester (TPA) treatment. Scatchard analysis of 125I-labeled IGF-I to FLG 29.1 cells revealed the presence of a single high affinity binding site in both untreated and TPA-treated cells with a similar Kd value (0.3 +/- 0.2 nmol/L and 0.4 +/- 0.1 nmol/L, respectively). In untreated cells, IGF-I binding capacity (1.43 +/- 0.41 fmol/10(6) cells) was significantly (p < 0.05) lower than in TPA-treated cells (2.62 +/- 0.87 fmol/10(6) cells). Competition analyses and crosslinking studies revealed the presence of type I IGF receptor both in untreated and TPA-treated cells. Northern analysis demonstrated that mRNA for IGF-I receptor was expressed by both untreated and TPA-treated FLG 29.1 cells. In addition, FLG 29.1 cells released in the conditioned medium IGFBP-2 and IGFBP-4, whose expression was increased by TPA treatment as demonstrated by ligand and immunoblot analyses. The previous observations of chemotactic action of IGF-I on FLG 29.1 cells was confirmed by ultrastructural observations. Indeed, these cells revealed a marked migratory activity in response to nanomolar concentrations of IGF-I. In addition, the IGF-I receptor alpha IR-3 antiserum inhibited the IGF-I-induced FLG 29.1 cell's migratory activity. These findings clearly show that type IIGF receptor is expressed by osteoclast precursors and that IGF-I induces migration of these through the binding to type I IGF receptors. Binding proteins expressed by osteoclast precursors may play an autocrine role in modulating the IGF-I bioeffects.

Pigeons were made anosmic by unilateral treatment of their olfactory mucosa with a zinc sulphate solution and by plugging the contralateral nostril. In a series of releases at unfamiliar sites, 55&shy;79 km from the home loft, the experimental birds' homing behaviour was compared with that of two control groups: unmanipulated control birds, and birds subjected to unilateral zinc sulphate treatment and equipped with an ipsilateral nasal plug. The experimental pigeons exhibited homing behaviour &shy; in terms of both homeward initial orientation and homing performance &shy; significantly poorer than that of both unmanipulated and treated control pigeons. In addition, the homing behaviour of the treated controls turned out to be only slightly, and not significantly, poorer than that of the unmanipulated birds. The results show that the impaired homing capabilities of the zinc-sulphate-treated birds are due to the lack of navigational information and not to non-specific brain damage caused by the experimental treatment.

Background: Succinylcholine is contraindicated in "open eye" surgery because it raises intraocular pressure. High dose vecuronium reduces onset time for orothracheal intubation. The objective of the study was to evaluate clinical efficacy of high dose vecuronium (0.2 and 0.3 mg/kg) and its effects on intraocular pressure for its use in "open eye" emergency surgery., Design: Randomized, prospective, clinical trial., Setting: Eye clinic of University of Florence., Patients: 40 patients scheduled for vitrectomy, excluding any drug action on IOP, subdivided into two groups: the first (20 patients) had 0.2 mg/kg vecuronium at the induction of anaesthesia, the second (20 patients) 0.3 mg/kg. ANAESTHESIA: Premedication: atropine 0.01 mg/kg. Preinduction: fentanyl 3 micrograms/kg. Induction: thiopentone 4 mg/kg+ after 1 minute) vecuronium. Orotracheal intubation after 90"., Measures: IOP was obtained by applanation tonometry in three time: T0 = preinduction; T1 = 50" after thiopentone; T2 = 50" after vecuronium. Systodiatolic pressure was obtained at the same time. Neuromuscular function was evaluated by vocals cord relaxation and by clinical evaluation of response to ulnar nerve stimulation (by train of four)., Statistic: "t"-Student., Main Results and Conclusions: No modification of IOP and systodiastolic pressure was caused by administration of vecuronium; no statistic differences are between T1 and T2 values. All patients were intubated after 90" vecuronium administration; the vocal cord relaxation was maxima in all the patients. High dose vecuronium seems to be useful in "open eye" emergency surgery when succinylcholine is contraindicated.

Osteoblasts are involved in the bone resorption process by regulating osteoclast maturation and activity. In order to elucidate the mechanisms underlying osteoblast/preosteoclast cell interactions, we developed an in vitro model of co-cultured human clonal cell lines of osteoclast precursors (FLG 29.1) and osteoblastic cells (Saos-2), and evaluated the migratory, adhesive, cytochemical, morphological, and biochemical properties of the co-cultured cells. In Boyden chemotactic chambers, FLG 29.1 cells exhibited a marked migratory response toward the Saos-2 cells. Moreover, they preferentially adhered to the osteoblastic monolayer. Direct co-culture of the two cell types induced: (1) positive staining for tartrate-resistant acid phosphatase in FLG 29.1 cells; (2) a decrease of the alkaline phosphatase activity expressed by Saos-2 cells; (3) the appearance of typical ultrastructural features of mature osteoclasts in FLG 29.1 cells; (4) the release into the culture medium of granulocyte-macrophage colony stimulating factor. The addition of parathyroid hormone to the co-culture further potentiated the differentiation of the preosteoclasts, the cells tending to fuse into large multinucleated elements. These in vitro interactions between osteoblasts and osteoclast precursors offer a new model for studying the mechanisms that control osteoclastogenesis in bone tissue.

LY 139478, the hydrochloride salt of LY 117018, is a member of the nonsteroidal antiestrogens, benzothiophene derivatives, described to be full estrogen agonists in bone acting via an estrogen receptor-mediated mechanism. However, the cellular actions of these compounds on bone remodelling need to be established. To investigate the "in vitro" properties of LY 139478 on osteoclast precursors, the human pre-osteoclastic cell line FLG 29.1 was examined for evidence of bioeffects of this compound. Binding studies with tritiated 17 beta-estradiol (17 beta E2) demonstrated that the relative potency of LY 139478 in inhibiting estrogen binding to its receptor was equal to that of 17 beta E2. Significant (p < 0.05) dose-dependent inhibition of cell growth was induced by LY 139478 at 10 nM, 100 nM and 1 microM. Calcitonin-induced cAMP accumulation was significantly increased by low (1 pM) and high (1 microM) doses of both 17 beta E2 and the compound with a dose-dependent response. Differently than estrogen, LY 139478 at high dose significantly reduced IL-6 release by these cells. In addition, pharmacological doses of both 17 beta E2 and LY 139478 activated apoptotic cell death. These findings show that the benzothiophene-derived LY 139478 acts directly on the human pre-osteoclastic cell line FLG 29.1 as an estrogen agonist.

The primary biological effect of the estrogen estradiol-17 beta (17 beta E2) on bone is to decrease bone resorption. However, whether 17 beta E2 affects osteoclast differentiation or function directly or through its action on osteoblasts is unclear. To investigate this question we examined the human preosteoclastic cell line FLG 29.1 for evidence of functional estrogen receptors (ERs). Southern blotting of reverse transcription-PCR amplification products with a 32P-labeled cDNA probe for the human ER mRNA demonstrated that FLG 29.1 cells express ER mRNA. Binding of [3H]17 beta E2 to nuclear ERs was steroid specific with approximately 400 saturable, high affinity (Kd approximately 1 nM) binding sites per cell nucleus. Nuclear ERs covalently labeled with [3H]tamoxifen aziridine showed an apparent molecular weight of 65,000 by SDS/PAGE and Western blotting with the D75 monoclonal antibody to human ER. Pretreatment of cells with 0.1, 1.0, or 10 nM 17 beta E2 induced a dose- and time-dependent specific binding of progesterone to FGL 29.1 cells, and stimulation of the cells with 10 nM and 100 nM 17 beta E2 significantly (P < 0.05) reduced cell proliferation. Transcriptional activity of the ER gene was detected by transient transfection of cells with the pERE-BLCAT plasmid containing the estrogen response element for the vitellogenin A2 gene and the bacterial chloramphenicol acetyltransferase reporter gene. Treatment of FLG 29.1 cells with 10 nM 17 beta E2 increased chloroamphenicol acetyltransferase expression from 5- to 29-fold compared to controls. These observations suggest a potential role for estrogen in osteoclastogenesis.

Estrogen replacement therapy is effective in the prevention of postmenopausal osteoporosis, and a direct action of 17-beta-estradiol (17 beta E2) on osteoblastic and osteoclastic cells has been demonstrated. The inhibition of bone resorption by ipriflavone (IP), an isoflavone derivative devoid of estrogenic properties but active in potentiating the effects of estrogen on bone tissue, has been shown in in vitro and in vivo studies and confirmed by clinical data. To investigate the molecular mechanisms that underlie IP effect, we studied the possible interactions of IP and its four main in vivo metabolites (I, II, III, and V) with the estrogen receptor (ER) in the human preosteoclastic cell line FLG 29.1, whose growth and function are modulated by the compound. In parallel experiments, the human breast cancer cell line MCF7 was also analyzed. IP binding sites were demonstrated in the nuclear fraction of FLG 29.1 cells. 17 beta E2 and other steroid compounds failed to displace IP binding to intact FLG 29.1 cells. Similarly, IP and metabolites I, III, and V were not able to displace 17 beta E2 binding to intact MCF7 cells, whereas metabolite II showed an IC50 of 61 nM. 17 beta E2 binding to FLG 29.1 cells was increased after preincubation with metabolites I, III, and V. IP and its metabolites did not induce ER-dependent gene expression in FLG 29.1 and MCF7 cells transfected with a reporter gene and an estrogen response element (ERE).(ABSTRACT TRUNCATED AT 250 WORDS)

The role of vascularization in the process of bone resorption has not been clarified. The interactions between vascular endothelium and osteoclast progenitors were analyzed using clonal cell lines of bone-derived endothelial and preosteoclastic cells. Insulin-like growth factor I is a major chemotactic stimulator of preosteoclastic cell migration mediated by bone endothelial cells. Osteoclast precursors rapidly adhered to bone endothelial monolayers. This phenomenon appeared to be cell-specific and mediated through the binding of vitronectin and fibronectin receptors to fibronectin. In addition, direct contact with bone endothelial cells induced osteoclast progenitors to differentiate into more mature elements, with the tendency to cluster together to form large multinucleated cells. These findings demonstrated specific in vitro interactions between bone endothelial cells and osteoclast progenitors, offering a new model for understanding the molecular mechanisms which direct the processes of osteoclast recruitment and ontogeny.

A direction recorder, which can be carried by a flying bird on its back, has been used for the first time on a wild species. The device can detect and record the direction in which a bird is heading during flight. Cory's shearwaters (Calonectris diomedea) were moved from their nesting colony to five different sites and fitted with direction recorders, and four homing flight paths were obtained. Our data show that the displaced birds were able to assume and maintain a homeward course soon after release over large areas of open sea, completely devoid of guiding features; topographical elements are, therefore, not necessary for correct orientation.

Chronic gastritis may favour the development of gastric cancer more as a condition than as precancerous lesion. Since, in most cases, it is pathologically correlated with Helicobacter pylori infection, it is reasonable to postulate at least an indirect role for this organism in the pathogenesis of gastric cancer. H. pylori, however, is only one of the risk factors involved, in that additional factors (excess salt, cigarette smoking, deficiency of foodstuffs with an antioxidizing effect) may facilitate the malignant transformation of chronic atrophic gastritis into intestinal-type gastric cancer. Gastric carcinogenesis therefore presents itself as a multifactorial, multistage process, furthered by the occurrence of precancerous lesions which are usually interrelated (type-III intestinal metaplasia, severe dysplasia) and by functional alterations such as achlorhydria, which, though it is not enough in itself to cause gastric cancer, promotes abnormal intragastric bacterial development, a condition which may be followed by abnormal intragastric formation of cancerogenous nitroso compounds. The existence of a close correlation between both gastric cancer and H. pylori infection and low socio-economic and hygienic status of the population lends further strength to the hypothesis that an "H. pylori factor" is involved in gastric carcinogenesis. Consequently, to reduce the risk of gastric cancer, various strategies have been devised to prevent H. pylori infection (improvement in socio-environmental conditions, anti-H. pylori vaccine) and/or to eradicate the organism (by means of therapeutic regimens including antimicrobial agents, which, however, can be implemented only in patients who have not developed diffuse atrophy and/or dysplasia, in whom H. pylori may no longer be detectable). Definitive proof of the real extent of the relationship between H. pylori and gastric cancer and of the efficacy of therapeutic and preventive measures can be provided only by controlled trials in populations with a high prevalence of chronic non-atrophic gastritis which are difficult to organize.

Ipriflavone, a synthetic isoflavone derivative, reduces bone resorption by inhibiting osteoclasts activity. In order to evaluate the role of Ipriflavone on osteoclast growth and differentiation, we tested Ipriflavone and its four "in vivo" main metabolites (Metabolites I, II, III, and V) on a clonal population of human osteoclast precursor cells (FLG 29.1). Pharmacological doses of Ipriflavone and Metabolite III were able to inhibit cell proliferation and interleukin 6 release. In co-cultures of FLG 29.1 cells and osteoblastic (Saos-2) cells Ipriflavone at 1 microM dose inhibited the adhesion of FLG 29.1 cells to the osteoblastic monolayer and reduced the immunocytochemical reaction of the vitronectin receptor. Binding studies with tritiated Ipriflavone showed the presence of a single specific binding site, wtih a Kd of about 70 nM and a binding capacity of 8 fmol/10(6) cells. These results demonstrate a direct effect of Ipriflavone and of Metabolite III on the human osteoclast precursor cell line FLG 29.1.

A case of spermatic cord liposarcoma is reviewed. Radical orchiectomy is an adequate form of treatment while retroperitoneal lymphadenectomy and adjunctive radiotherapy or chemotherapy appear to be controversial. A close follow-up is mandatory to detect early relapses or distant metastasis.

Recent clinical and toxicological studies have investigated the mineralcorticoid-like and hypertensive effects of liquorice, and we therefore set out to identify the active component responsible for these effects. We conducted a 30-day comparative analysis of glycyrrhizin and 18 beta-glycyrrhetinic acid and found that the latter causes significant variations both in systolic blood pressure and in the excretion in the urine of Ca++. The effects were fully reversible on suspension of treatment.

It is now widely accepted that insulin-like growth factor-I (IGF-I) has a local regulatory role in bone remodeling. IGF-I has also been demonstrated to regulate proliferation of bone-derived endothelial cells. Such studies suggest a role of IGF-I in skeletal angiogenesis. Using BBE cells, a bovine bone endothelial cell line, we characterized the kinetics and chemical properties of IGF-I receptors and examined the effect of IGF-I on bone endothelium migration. Two classes of binding sites with high affinity for IGF-I were detected by binding experiments on bone endothelial cells. Both competition analyses and cross-linking studies revealed the presence of type I IGF receptor in bone endothelial cells. Moreover, these cells produced and released authentic IGF-I into the medium, as evidenced by radioimmunoassay analyses of gel-filtered conditioned media. Both IGF-I binding capacity and release decreased either with increases in cell number or after treatment with 17 beta-estradiol (17 beta E2) and parathyroid hormone (PTH). Both hormones also inhibited chemotactic responses of bone endothelial cells to IGF-I. Taken together, these results strongly suggest that IGF-I, a growth factor that promotes the proliferation of various bone cell types, also induces growth and chemotactic responses in bone endothelium acting through the type I IGF receptor. This may be part of a generalized response of bone cells to IGF-I that facilitates cell migration.

Objective: The reflex response to orotracheal intubation provokes an increase of arterial pressure accompanied by an increase of chorioides volume and a consequent ocular hypertone. There are several methods to reduce the reflex response due to intubation. One of the most effective is topical anaesthesia of larynx and trachea. Experiments were directed to evaluate the efficacy of topical anaesthesia to reduce the intraocular hypertone due to orotracheal intubation., Design: A prospective randomized mask study was conduct on patients undergoing ophthalmologic (anterior segment) surgery at the Eye Clinic of Florence University., Methods: Intraocular pressure was measured by a Goldman tonometer at four times: T0 = basal, T1 = 2' minutes after induction of general anaesthesia, T2 = 2' minutes after laryngoscopy, T3 = 2' minutes after orotracheal intubation. At the same moments, systolic blood pressure, heart rate, rate pressure pro duct were measured. Patients were randomly divided in two groups: Group L (n = 10) in which was evaluated the efficacy of laryngotracheal topical spray of lidocaine 4% (2 ml) and Group F (n = 10) in which saline was used instead of anesthetic. The filling of the LTA kit (Abbott) was made by a person not involved in the experiments., Data Analysis: Student's t test for unpaired data., Results: Topical anaesthesia reduces the increase of intraocular pressure, hypertension and rate pressure product due to intubation. The intraocular pressure reduces to 13% less than basal value in Group L and increase to 50% more than basal value in Group F., Conclusion: The topical anaesthesia of larynx and trachea is effective to reduce the intraocular hypertension due to the reflex response evoked by orotracheal intubation.

The effects of Glycyrrhiza glabra L. extract, glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids on the mutagenicity of the ethyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, and ribose-lysine Maillard model systems were investigated by using the Salmonella/microsome reversion assay. The protocol used allowed us to detect desmutagenic and antimutagenic activity and to avoid false positive results due to toxicity. For all the compounds tested, no desmutagenic activity was observed against ethyl methanesulfonate and N-methyl-N'-nitro-N-nitrosoguanidine; only Glycyrrhiza glabra extract showed antimutagenic activity against ethyl methanesulfonate. On using the ribose-lysine mutagenic browning mixture, the desmutagenic activities of the Glycyrrhiza glabra extract, glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids were observed. 18 beta-Glycyrrhetinic acid was the most active compound. Glycyrrhiza glabra extract also exhibited antimutagenic activity against ribose-lysine.

We report a case of sacral chordoma with numerous skin metastases. Histologically they show the typical 'physaliform cells' expressing simultaneously cytokeratin, S-100 protein, epithelial membrane antigen and vimentin immunoreactivity.

A number of studies have demonstrated the pivotal role of collagen molecules in modulating cell growth and differentiation. In order to analyze the direct effects of collagen type I on the osteoblastic phenotype, we have devised an in vitro culture system for studying the interactions between bovine collagen type I and Saos-2 cells, a human osteoblastic cell line. Saos-2 cells were cultured both on top of collagen-coated culture dishes as well as inside a three-dimensional collagen network. Plating on dishes treated with collagen induced maximal adhesion of Saos-2 cells after 24-hour incubation. Cells cultured on collagen gel matrix expressed about 2.5-fold more alkaline phosphatase when compared with untreated plastic dishes. On collagen-coated dishes the responsiveness of Saos-2 cells to parathyroid hormone was decreased, whereas no modifications were observed in the effect of vasoactive intestinal peptide on these cells. Using a microfluorimetric measurement of DNA, an increase of proliferation was observed in Saos-2 cells cultured on collagen gel. Saos-2 cells were also able to colonize collagen sponges and in this three-dimensional network they were able to synthesize osteocalcin, as assessed both by immunocytochemistry and radioimmunoassay. In this study we have demonstrated that bovine collagen type I exhibits favorable effects on attachment and functional and growth activities of a human osteoblastic cell line, encouraging its use as a bone graft material.

In view of the pharmacological interest in phenolic substances, we have determined the total amount of anthocyanins and polyphenols present in the berries of several cultivars of Ribes, Rubus, and Vaccinium genera. The in vitro antiradical activity of the crude extracts on chemically-generated superoxide radicals as well as the inhibitory activity towards the enzyme xanthine oxidase were studied. All the crude extracts examined showed a remarkably high activity towards chemically-generated superoxide radicals. The activities were greater than those expected on the basis of the quantities of anthocyanins and polyphenols present in the samples. Furthermore, the extracts showed a certain inhibitory activity towards xanthine oxidase. Ribes nigrum extracts exhibit the highest activity, being the richest in both anthocyanins and polyphenols. On the other hand, Ribes rubrum extracts seem to contain more active substances than the other crude extracts.

An HPTLC method is described for the simultaneous determination of glycyrrhizinic acid tripotassium salt (3K-G), 18 alpha- and 18 beta-glycyrrhetinic acid (18 alpha-GA, 18 beta-GA) in rat plasma, after oral administration of 3K-G (30 mg/kg once a day for 30 days). Systolic pressure and the volume of urine excreted in 24 hours were recorded during this period to observe any drug-induced effects.

The relationship between Helicobacter pylori (HP) and gastric ulcer therapy is examined by analyzing both the data that suggest that eradication of HP renders the gastric mucosa less susceptible to development of gastric ulcer as well as the substantial body of evidence that does not support this contention. The results reported in clinical trials with colloidal bismuth citrate, antimicrobial agents (furazolidone), and combinations of anti-ulcer and antimicrobial agents (H2-antagonist+cefixime, H2-antagonist+metronidazole) are reviewed. Also analyzed is the relationship between HP eradication and ulcer recurrence. Only one study is available on this aspect, and the limited evidence it provides in favour of a prophylactic effect of eradication therapy is not entirely convincing. The authors conclude that there is no reasonable case for the dogmatic assumption that eradication of HP facilitates either acute healing or long-term prophylaxis of gastric ulcer, though certain subgroups of gastric ulcer patients may benefit from eradication therapy.

Protective effects of ipriflavone, an isoflavone derivative, in osteoporosis are believed to be caused by the inhibitory action on bone resorption. A direct effect of ipriflavone on bone formation is as yet unknown. Ipriflavone and four of its metabolites (I, II, III, and V) were examined for their effects on parathyroid hormone response, collagen synthesis, alkaline phosphatase activity, and cell proliferation in a clonal cell population of rat osteoblastic cells. Pretreatment of osteoblasts with high concentrations of ipriflavone for 48 h significantly inhibited the cAMP response to parathyroid hormone, producing a shift in the dose-response curve; at lower concentrations metabolites II and III potentiated the cAMP accumulation induced by low doses of parathyroid hormone. The 48 h treatment with metabolite V at the 1 nM dose significantly stimulated collagen synthesis in osteoblastic cells. Ipriflavone and metabolite I showed a biphasic stimulatory action on the alkaline phosphatase activity of osteoblasts, with a maximal effect at the 0.1 and 1 nM doses, respectively. A similar biphasic response was observed with ipriflavone and metabolite I on osteoblastic cell growth, with a maximal effect at the 0.1 nM concentration. These results suggest a direct role of ipriflavone in modulating the synthetic and growth properties of osteoblast-like cells.

According to the traditional view gastric acid and pepsin are a sine qua non for ulcer development. Acid suppression, however, is far from being the only successful therapeutic approach, and similar healing rates are achieved by drugs with substantially different mechanisms of action--antacids, H2-antagonists, antimuscarinics, cytoprotective and site-protective agents--thus denoting a multifactorial pathogenesis. Even with the antisecretory compounds, the relationship between gastric acid and ulcer healing gives rise to perplexity: antacids prove effective at widely varying doses; pirenzipine and H2-blockers, which are clinically equieffective, differ considerably in antisecretory efficacy; H2-antagonist studies on early vs late postprandial dosing yield contradictory clinical results; morning and bedtime single administrations of H2-antagonists prove equiactive on ulcer healing, leading to a reappraisal of the alleged importance of nocturnal acidity. Ulcer sealants such as colloidal bismuth and sucralfate prove as effective as H2-antagonists despite their total lack of antisecretory activity, thereby apparently undermining the primary pathogenetic role of acid. However, with the spectacular 100% healing rates achieved by the protonpump blocker, omeprazole, the wheel has come full circle, and gastric acid appears to re-emerge as a primary element in pathogenesis. Specific therapy, based on the predominant pathogenetic factor involved, is likely to be a feasible proposition, but, at present, remains little more than a remote possibility.

The Authors report 28 cases of scrotal traumas evaluated during a period of 5 years on an amount of 1.100 scrotal echography: 5 patients with severe scrotal trauma are investigated with echography within 2 hours while the others between 1 and 6 days. Some cases of overlooked trauma were studied some months later. In their experience the authors underline the importance of echography in early diagnosis of scrotal contents lesions which need a surgical exploration and those which allow a medical treatment. Also ultrasound investigation is important in evaluating and in the follow-up the scrotal content lesions caused by trauma.

The Authors report 3 cases of penile trauma observed in a period of 6 months. The patients were studied by penile echography and cavernosography. In this series+ echotomography resulted more accurate than cavernosography which gave always negative results.

Genotoxic properties of essential oils from Anthemis nobilis L., Artemisia dracunculus L., Salvia officinalis L., Salvia sclarea L., Satureja hortensis L., Satureja montana L., Thymus capitatus L., Thymus citriodorus Schreb., Thymus vulgaris L., Citrus bergamia Risso, were studied with Bacillus subtilis rec-assay and Salmonella/microsome reversion assay. The essential oil of Artemisia dracunculus L. "Piemontese" turned out to be active in the rec-assay but not in the Salmonella test. DNA-damaging activity was demonstrated to be due to the estragol component of the oil. Advantages of the combined use of these two short-term microbial assays in genotoxic studies are discussed.

Less attention has been devoted to the effects of antisecretory agents on pepsin secretion than to those on gastric acid secretion, particularly in human subjects. Moreover, comparison of the various trials is far from being simple and straightforward owing to the fact that the studies available present substantial variability in terms of types of subjects (controls, DU patients), gastric secretion (basal, stimulated), type of stimulation (pentagastrin, histamine, insulin, meals, sham feeding) antisecretory drug administration route (oral, i.v.) and considered parameters (concentration, output). This review of the published data reveals that all antisecretory agents reduce pepsin output, regardless of their sometimes very different mechanism of action. Despite this, there are differences in antisecretory effects according to the agent used to stimulate gastric secretion. Even within a single drug class (H2-antagonists, prostaglandins) there may be differences depending on the potency of the compound used.

In an attempt to explain apparent differences in the pigeon homing behaviour over different regions, some experiments with anosmatic birds have been repeated on German birds. The poor initial orientation in either controls or experimentals in many single experiments and in pooled data was an insufficient basis for the evaluation of the influence of olfactory deprivation on homeward directedness. Homing success, however, was significantly worse in experimentals than in controls, which confirmed the result of impaired homing ability of anosmatic pigeons.

After a brief examination of the recent literature on plasma cell leukemia, the Authors describe the clinical features and the ultrastructural findings of the peripheral blood plasma cells, examined with transmission (T.E.M.) and scanning (S.E.M.) electron microscopes, of two patients with acute plasma cell leukemia. Both of them had a previous history of myeloma. T.E.M. confirmed the diagnostic value of the asynchronous plasma cells, and S.E.M. showed the characteristic microvilli and blebs, previously observed.