alpha-MSH production, receptors, and influence on neopterin in a human monocyte/macrophage cell line.

alpha-Melanocyte-stimulating hormone (alpha-MSH), a tridecapeptide derived from pro-opiomelanocortin, has potent antiinflammatory activity in laboratory animals. alpha-MSH inhibits nitric oxide production by murine macrophages, an influence believed to reflect activation of an autocrine circuit in these cells, one that is based on production and release of alpha-MSH and subsequent stimulation of melanocortin receptors. We found that THP-1 cells, human monocytic cells, produced alpha-MSH; this production was increased by interleukin-6, tumor necrosis factor a, or concanavalin A. These cells also expressed the gene for the human alpha-MSH receptor MC1. Unlike murine macrophages, THP-1 cells produced little nitrite in response to interferon-gamma (IFN-gamma) and lipopolysaccharide, and a-MSH inhibited this production only slightly. However, production of neopterin, a presumed primate homologue of nitric oxide in lower animals, was increased in THP-1 cells stimulated with INF-gamma plus TNF-alpha and alpha-MSH significantly inhibited this production. The evidence indicates that an autocrine regulatory circuit based on alpha-MSH occurs in human monocyte/macrophages much as in murine macrophages. alpha-MSH-induced modulation of specific inflammatory mediators/cytotoxic agents appears to differ depending on the importance of the mediators in the myelomonocytic cells of different species.

Elevation of plasma ACTH concentration in rabbits made febrile by systemic injection of bacterial endotoxin.

This study was carried out to investigate the adrenocorticotropic hormone (ACTH) response in rabbits made febrile by systemic injection of lipopolysaccharide (LPS, Salmonella typhosa endotoxin). Intravenous (i.v.) injection of LPS (0.1 microgram/kg and 1.0 microgram/kg) increased rectal temperature (biphasic fever) and the plasma concentration of ACTH (ACTH response) in a dose-related manner. These responses were suppressed by pretreatment with indomethacin (20 mg/kg, subcutaneously). Intracerebroventricular (i.c.v.) administration of indomethacin (400 micrograms) had no effect on the ACTH response to LPS, although it significantly suppressed febrile response. Small increases in plasma concentration of ACTH and significant fevers followed i.c.v. administration of prostaglandin E2 (2 micrograms) or F2 alpha (2 micrograms). I.v. administration of corticotropin releasing factor (CRF) antagonist [alpha-helical CRF (9-41) (200 micrograms/kg)] partly suppressed the ACTH increase induced in plasma by i.v. LPS. These results suggest that prostaglandins synthesized outside the blood-brain barrier play an important role in the ACTH response and that the mechanism for induction of the ACTH response is not exactly the same as that for the febrile response, although prostaglandins are involved in both responses.

[Ventilation and continued positive-pressure respiration in resuscitation]. / La ventilazione a pressione positiva continua in rianimazione

Expiratory positive pressured used as a routine procedure in patients with healthy lungs and those with serious pulmonary alterations since 1973 is described. It has been found that CPPV offers effective opposition to the gradual desaturation of arterial blood in O2 encountered with IPPV.

[The use of althesin in endoscopy]. / Utilizzazione dell'Althesin nelle pratiche endoscopiche.

Althesin was used on account of its pharmacokinetic and pharmacodynamic properties and its high therapeutic index in a search for a narcotic drug displaying minimal interference with metabolic and functional parameters in the aged. Continuous perfusion of the anaesthetic proved an extremely flexible method bearing in mind the varying length of the operations concerned. Stress is laid on the need for clinical control, especially at the moment of induction to ensure that timely action can be taken in the event of complications.

[Electric stimulation of the heart : treatment indications and criteria for choosing of pacemakers. Contribution of the Ospedale Santa Croce in Cuneo]. / L'elettrostimolazione cardiaca: indicazioni al trattamento e criteri di scelta dei pace-makers. Contributo dell'Ospedale Santa Croce di Cuneo

The various types of emergency electrical heart stimulation for the short and medium terms or permanent, are reviewed along with choice criteria. The personal series represting 5 years experience at the Cuneo S. Croce Hospital is reported.

Central neurogenic antiinflammatory action of alpha-MSH: modulation of peripheral inflammation induced by cytokines and other mediators of inflammation.

The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) has potent antipyretic and antiinflammatory properties. When administered systemically, the naturally occurring molecule and its COOH-terminal tripeptide sequence inhibit inflammation induced by peripherally applied irritants and intradermal injections of mediators of inflammation such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha). We recently found that alpha-MSH can act solely within the brain to inhibit inflammation caused by a general irritant applied to the skin. This activity appears to be shared with salicylate drugs and the combined observations suggest the existence of descending neurogenic antiinflammatory signals capable of modulating inflammation in peripheral tissues. To improve our knowledge of the scope of this action of the peptide, alpha-MSH was injected into the cerebral ventricles (i.c.v.) of mice that had received intradermal injections in the ear of mediators of inflammation: IL-1 beta, IL-8, leukotriene B4, and platelet-activating factor. The centrally administered peptide inhibited the actions of all of these proinflammatory agents as determined from comparisons with measures of ear edema over time in control animals; this indicates that the central peptide can alter inflammation induced in the periphery by major mediators of inflammation. In tests confined to IL-1 beta, central administration of alpha-MSH(11-13) was also effective. These findings support the concept of a descending neurogenic antiinflammatory influence promoted by an action of alpha-MSH within the brain, an inhibitory influence that is not restricted to modulation of just one or a limited set of the mediators of inflammation.

Determination of vincamine in human plasma by high-performance liquid chromatography with ultraviolet detection.

A simple and rapid high-performance liquid chromatographic method was developed for the determination of vincamine in human plasma. Plasma samples were buffered at pH 9 and after extraction with tert.-butyl methyl ether back-extracted into 0.017 M orthophosphoric acid. Propranolol was used as the internal standard. An aliquot was injected on to a high-performance liquid chromatographic system using a C18 reversed-phase column and an acetonitrile-phosphate buffer containing triethylamine (30:70) as mobile phase. Detection was performed with an ultraviolet detector at 273 nm. The method had good accuracy and precision and the detection limit (0.3 ng/ml with a signal-to-noise ratio of 3:1) allowed the assessment of vincamine concentrations in plasma in pharmacokinetic studies on healthy human volunteers.

[Hypokalemic states in clinical practice. A case of severe hypokalemia combined with flaccid quadriplegia]. / Gli stti ipokaliemici in clinica. Presentazione di un caso di grave ipokaliemia con tetraparesi flaccida.

The biochemical data relating to the physiological distribution of potassium and its regulating factors in the normal human body are explained. Reference is then made to the clinical symptoms and aetiopathogenesis of hypokalaemia. A serious case coupled with flaccid quadriplegia in a 34-yr-old male is presented. Stress is laid on the usefulness of correct investigation of the history, and the fundamental resort to complete electrolytic screening in patients presenting with polyuria, polydipsia, arrhythmia and flaccid quadriplegia.

[Computerized tomography and conventional radiography in the diagnosis of destructive spondyloarthropathy. Our experience with 30 patients undergoing periodic hemodialysis]. / Tomografia computerizzata e radiografia tradizionale nella diagnosi della spondiloartropatia destruente. Nostra esperienza in 30 pazienti sottoposti a emodialisi periodica.

Thirty patients of both sexes (15 males and 15 females) with chronic renal failure who had under gone hemodialysis for 2-184 months (mean 45.1 months) were examined with conventional radiographs of the cervical spine and thin-layer CT of C4-C5-C6 to evaluate the radiographic patterns of destructive spondyloarthropathy. The radiographic patterns obtained with conventional and CT exams were compared with one another and with clinical (carpal tunnel syndrome) and biochemical data (alkaline phosphatase, parathormon, Ca, P, Ca/P, Al, beta 2-microglobulin). DSA (erosion and narrowing of the intervertebral space, collapse of the vertebral body and erosion of the vertebral plates) was recognized in 7 patients with conventional radiographs and in 11 patients with CT thanks to greater CT capabilities to recognize minimal osteolytic lesions of the vertebral body. All the patients with destructive spondyloarthropathy had personal and hemodialysis age higher than those without destructive spondyloarthropathy: 59.3 vs 57.7 years; 49 vs 39 months. Parathormon and alkaline phosphatase were increased while beta 2-microglobulin was normal. Only 2 patients with DSA had carpal tunnel syndrome. In conclusion, CT is a valuable technique for the diagnosis of destructive spondyloarthropathy but it must be performed only after conventional radiographs of the cervical spine or in the presence of clinical signs of destructive spondyloarthropathy (parathormon and beta 2-microglobulin increased, long-term hemodialysis).

The neuropeptide alpha-melanocyte-stimulating hormone inhibits experimental arthritis in rats.

alpha-Melanocyte-stimulating hormone (alpha-MSH) modulates inflammatory processes in models of acute inflammation and in models of sepsis/septic shock/adult respiratory-distress syndrome (ARDS). Because this neuropeptide inhibits actions of cytokines and other mediators of imflammation that are also believed to underlie aspects of chronic inflammation, tests were performed to compare the effects of repeated administration of the peptide with those of prednisolone and saline on the development of adjuvant arthritis in rats. alpha-MSH (50 micrograms), injected i.p. twice daily, markedly inhibited the clinical and histological signs of experimental arthritis and moderated the weight loss observed in control animals. Prednisolone (100 mg/kg), given twice per day, prevented development of arthritis but caused marked and progressive weight loss. The results confirm the potent anti-inflammatory influence of alpha-MSH, in this case in a model of chronic inflammation that has immune components.

Binding of anti-inflammatory alpha-melanocyte-stimulating-hormone peptides and proinflammatory cytokines to receptors on melanoma cells.

alpha-Melanocyte-stimulating hormone (alpha-MSH1-13), a peptide derived from proopiomelanocortin, has remarkable anti-inflammatory and antipyretic activities. This peptide and a tripeptide that forms the COOH-terminal portion of the molecule (alpha-MSH11-13; Lys Pro Val) inhibit inflammation when given centrally or peripherally. Because of the similarity in their actions, the tripeptide has been presumed to be the amino acid message sequence underlying the effects of alpha-MSH1-13. To test the possibility that the two peptides occupy the same receptors, competitive binding experiments were performed with B16 mouse melanoma cells that are known to have alpha-MSH1-13 receptors. In these experiments, alpha-MSH11-13 did not inhibit binding of a radiolabelled alpha-MSH1-13 analog. This finding suggests that alpha-MSH1-13 and alpha-MSH11-13 exert their anti-inflammatory/antipyretic/anticytokine effects via stimulation of separate receptors. Because alpha-MSH inhibits the effects of several cytokines including inflammation caused by interleukin (IL)-6 and IL-8, the capacity of these cytokines to compete for alpha-MSH binding sites was tested. There was no evidence that these proinflammatory cytokines bind to alpha-MSH receptors on murine melanoma cells. Although further tests with host cells involved in inflammation are required, the latter result is the first evidence that the mechanism of anticytokine action of alpha-MSH does not depend upon peptide/cytokine competition for binding sites.

[Percutaneous transluminal laser angioplasty. Initial clinical experience in 9 patients]. / L'angioplastica percutanea transluminale con laser. Iniziale esperienza clinica in 9 pazienti.

In this paper the authors report on a new technique--percutaneous transluminal laser angioplasty (PLR) which was performed on 9 patients with iliac and/or femoro-popliteal artery occlusion. All patients were males (mean age: 64.5 years) and had arterial occlusion (mean length: cm 12.5). PLR was performed with an argon laser (max power: 16 Watts). In 8 out of 9 patients (88.8%) a complete recanalization was obtained of the occluded arterial tract, without complications. In one case only (12.2%) there was an arterial wall perforation with unsatisfactory results. In our opinion, PLR has proven a simple methodology, which can be performed on any patient due to the very low incidence of severe complications and distal embolism. Moreover, PLR has quite low costs, and does not prevent eventual surgical/percutaneous interventions.

[Role of computed tomography in splenic blunt trauma]. / Il ruolo della Tomografia Computerizzata nei traumi chiusi della milza.

The CT scans of 18 patients (12 males and 6 females; mean age: 43.6 years) with splenic blunt trauma were reviewed. CT examinations had been made at different times after trauma. The CT images were grouped according to the time of examination and both structure and densitometry were evaluated in all lesions. In all cases CT findings were correlated with surgical and pathologic data. The patients were divided into two groups: group I included 11 subjects in whom CT had been performed within 48 hours following trauma and group II included 7 patients who had undergone CT at different times after trauma (3-13 days; mean: 6.5 days). All the lesions in group I exhibited blurred outlines, while the lesions in group II had clear-cut margins. The lesions in group I were always hyperdense while those in group II were hypodense. CT diagnosis was always in agreement with surgical findings. In conclusion, we confirm the value of CT in the examination of splenic lesions by blunt abdominal trauma. The evolution of splenic lesions is usually typical: CT yields useful information for injury evaluation and is therefore very important to plan treatment. We believe that CT should be performed as soon as possible, even on the basis of minor clinical and laboratory data.

[An analysis of a case series of 342 short-stature patients examined by the Tanner-Whitehouse 2 (TW2) method]. / Analisi della casistica di 342 pazienti con bassa statura esaminati con il metodo Tanner-Whitehouse 2 (TW2).

342 short-stature patients were examined to assess the agreement between anagraphic and bone ages. 190 men and 152 women (age range: 0 to 17.5 years) underwent conventional radiographs of the left wrist. The radiographs were studied with the TW2 method which provides an index of the skeletal maturity of short and long bones and a global index of the hand. The bone ages thus obtained were compared with anagraphic ages. Patients' statures were compared with their parents' ones. Finally, radiation exposures were evaluated. Anagraphic and bone ages were in agreement in 199 patients and in disagreement in 220. Three patients were adult. The short stature in 78 patients was in agreement with their parents' one, while 253 patients had at least one parent with normal stature. No comparison could be made in 11 patients. In conclusion, TW2 is a simple method to calculate bone age (in months and years) and to select the patients to submit to further examinations and to hormone therapy.

[Critical review of the diagnostic protocol in patients with head injury]. / Revisione critica del protocollo diagnostico nei pazienti con trauma cranico.

The results of a retrospective review of the conventional radiographs performed on head injury patients are reported. Skull radiography findings were compared with clinical symptoms and CT results, when CT was performed, to investigate the presence of intracranial lesions. The radiographs of 2,285 adult patients of both sexes were evaluated: skull fractures were observed in 21/2,285 patients (0.9%) only. CT was positive for an intracranial lesion in 18 of 21 patients (85.71%). Clinical symptoms were divided into three groups according to lesion severity and to neurologic impairment. 979 patients were asymptomatic and 1,306 were symptomatic: 1,114 patients were included in group I, their symptoms being nausea, vomit and loss of consciousness for less than ten minutes, 124 were included in group II (epistaxis and loss of consciousness for more than 10 minutes) and 68 were included in group III (coma and focal neurologic signs). All the patients in groups II and III and 30 patients in group I were submitted to CT--222 CT exams on the whole. Thirty-five patients in group III and 9 in group II had an intracranial lesion on CT, while CT findings were normal in all group-I patients. Thus, we conclude that the presence of a skull fracture is not always correlated with the presence of intracranial lesions. The latter are more likely to be correlated with clinical symptoms, especially coma and neurologic impairement. Therefore, the higher value is confirmed of the clinical examination than of conventional radiographs in head injury patients.

Antiinflammatory influences of alpha-MSH molecules: central neurogenic and peripheral actions.

alpha-Melanocyte-stimulating hormone (alpha-MSH1-13) and its COOH-terminal tripeptide alpha-MSH11-13 (Lys Pro Val) inhibit inflammation when administered systemically. Recent evidence indicates that alpha-MSH1-13 can likewise inhibit inflammation in the skin solely via an action within the brain. Because of the potential importance of this discovery to understanding the control of inflammation and because alpha-MSH molecules might be useful for treatment of inflammation, experiments were performed to learn more about the mechanisms of action of these peptides. In tests on inflammation induced in the mouse ear by intradermal injections of recombinant human interleukin-1 beta, alpha-MSH1-1-13 administered intracerebroventricularly effectively reduced inflammation. This effect of centrally administered alpha-MSH1-13 was inhibited by systemic injection of the nonspecific beta-adrenergic receptor blocker propranolol and by administration of a specific beta 2-adrenergic receptor antagonist; the effect was not altered by blockade of cholinergic, alpha-adrenergic, or beta 1-adrenergic receptors. In mice with inflammation induced in a hind paw and with the spinal cord transected, the antiinflammatory effect of centrally administered alpha-MSH1-13 was prevented, indicating that intact descending neuronal pathways are required for the antiinflammatory influence of the central peptide. Systemic injection of alpha-MSH1-13 in animals with spinal cord transection had a smaller and later antiinflammatory effect, which suggests that the molecule also has an action, albeit lesser, in the periphery. However, alpha-MSH11-13 injected intraperitoneally had marked antiinflammatory activity in animals with spinal cord transection.(ABSTRACT TRUNCATED AT 250 WORDS)

Blunt trauma of the spleen: the delayed rupture in computed tomography.

We retrospectively reviewed CT scans of 18 patients (12 males and 6 females; mean age: 43.6 years) with the diagnosis of blunt splenic trauma. All patients underwent CT at different times after the trauma. The cases were divided into 2 groups: according to the time at which the CT was performed, the 1st group consisted of 11 patients scanned within 48 h after the trauma; the 2nd group consisted of 7 patients studied with CT at variable times after the traumatic event (mean time: 6.5 days; range 3-13 days). All lesions in the 1st group (11 patients) had indistinct margins, while lesions of patients in the 2nd group (7 patients) always showed clean-cut and regular edges. Early lesions were always hyperdense, late ones hypodense. CT diagnosis always matched the surgeon's diagnosis. We can confirm the diagnostic value of CT of splenic lesions in blunt abdominal traumas.

Treatment of Helicobacter pylori and Chlamydia pneumoniae infections decreases fibrinogen plasma level in patients with ischemic heart disease.

BACKGROUND: Chronic Chlamydia pneumoniae and Helicobacter pylori infections could be a risk factor for ischemic heart disease (IHD), possibly by increasing fibrinogen levels. The aim of our study was to evaluate changes in fibrinogen level in patients with IHD and H pylori and/or C pneumoniae positivity randomly assigned to antibiotic treatment. METHODS AND RESULTS: Eighty-four patients with chronic IHD, H pylori and/or C pneumoniae antibodies, and normal acute-phase reactants were randomly assigned to treatment or no treatment. Treatment consisted of omeprazole, clarithromycin, and tinidazole in H pylori-positive patients and clarithromycin alone in C pneumoniae-positive patients. The effect of treatment and other baseline variables on fibrinogen levels, determined at 6 months, was evaluated by multivariate analysis. Treatment significantly reduced fibrinogen level at 6 months in the overall study population and in the groups of patients divided according to H pylori or C pneumoniae positivity. In the 43 treated patients, mean (+/-SD) basal fibrinogen was 3.65+/-0.58 g/L, and mean final fibrinogen was 3. 09+/-0.52 g/dL (P<0.001), whereas in the 41 untreated patients, mean basal and final fibrinogen levels were 3.45+/-0.70 and 3.61+/-0.71 g/L, respectively. The largest decrease was observed in patients with both infections. Fibrinogen changes were also significantly and negatively correlated with age. CONCLUSIONS: Our data suggest that a short, safe, and effective course of antibiotic therapy might be suggested as a means of interacting with an "emerging" risk factor.