Giuseppe Moscati: a man, a physician and a scientist.

The life of Giuseppe Moscati (1880-1927) as a man, as a physician and as a scientist may be framed within the cultural climate of Positivism, which spread over the last years of the 19th century and the beginning of the 20th Century. His activity contributed to patients' care improvement; in addition to meticulous drug regimens, he also prescribed a methodology of spiritual care, involving meditation and self-control as part of an holistic approach to healthcare. Our review deals with his published researches, highlighting the innovative findings on the juvenile diabetes treatment and extensive clinical changes consequent upon nephritis.

The long road to the use of microscope in clinical medicine in vivo: from early pioneering proposals to the modern perspectives of optical biopsy.

For a long period the scientists did not recognized the potentialities of the compound microscope in medicine. Only few scientists recognized the potentialities of the microscope for the medicine; among them G. Campani who proposed the utilization of his microscope to investigate the skin lesions directly on the patient.

Cancer-associated genodermatoses: skin neoplasms as clues to hereditary tumor syndromes.

Characteristic skin neoplasms are associated with a large number of hereditary tumor syndromes and their knowledge and early detection may facilitate the diagnosis of the underlying malignancies. We will review the clinical and dermatopathological aspects of cutaneous and visceral lesions and the recent progresses in understanding the etiology, pathogenesis and therapies of selected tumor syndromes. The skin neoplasms we chose to consider are multiple neurofibromas in neurofibromatosis, cylindromas and trichoepitheliomas in Broke-Spiegler syndrome, sebaceous tumors and keratoacanthomas in Muir-Torre syndrome, Gardner fibromas in Gardner syndrome, multiple basal cell carcinomas in nevoid basal cell carcinoma (Gorlin) syndrome, multiple tricholemmomas in Cowden syndrome, multiple fibrofolliculomas in Birt-Hogg-Dubé syndrome and multiple leiomyomas in hereditary leiomyomatosis and renal cell cancer.

Electron microscope study on a transmissible cytotoxic factor isolated from cerebrospinal fluid of neurological patients: analysis of its structure and of its effects on various types of cell cultures.

Aims: In previous studies, the present group showed that a factor, present in the cerebrospinal fluid of seven neuro-patients, was capable of inducing cell damages on cell cultures of epithelial cells (Vero), glial cells (DG54-MG) and human primary lymphocytes. The cytotoxicity, once induced, could be transmitted to fresh cell cultures using crude preparations obtained from the cytotoxic cell cultures.

Methods And Results: The present electron microscope study describes in detail the pathological changes occurring in the previously assayed cultured cell types, and for the first time in human fibroblasts, as a consequence of the treatment with crude cytotoxic preparation.

The diagnostic reliability of urinary cytology: a retrospective study.

The aim of this study was twofold. The first aim was to estimate the diagnostic reliability of urinary cytology for detection and management of urothelial neoplasms by using a specific preserving fluid for sample collection, and the liquid-based thin layer method for specimen preparation, the estimate was based on the correlation between the cytological findings of 10,000 non-hospitalized patients, and their histological diagnoses. A second aim was to compare the reliability of two instruments for thin-layer preparation, i.

AFM and FTIR spectroscopy investigation of the inverted hexagonal phase of cardiolipin.

Atomic force microscopy (AFM) and FTIR spectroscopy techniques have been exploited to investigate the inverted hexagonal phase (H(II)) of cardiolipin obtained by dehydration of a phospholipid water dispersion on a solid support. The characteristic cylinders of the H(II) phase have been imaged by AFM and the effects of different preparation conditions (temperature and the presence of chemicals) on the structural parameters and on the presence of local nanoscale defects have been studied. It has been found that the measured repeat spacing of the H(II) cylinders decreases upon increase of temperature and addition of pentachlorophenol (PCP), a chemical which is known to affect the structure and function of lipid bilayers.

A period of convergence in the studies on muscle contraction and relaxation: the Ebashi's contribution.

The object of this paper is to trace the growth of a fundamental problem that for a decade hindered the development of several lines of muscle research: the molecular mechanism that allows and controls contraction and relaxation of muscle fiber. Emphasis is placed on the difficulties to be overcome; thus the paper records not only the achievements and successes, but also the unavoidable failure and disappointments. The account highlights the essential contribution of Setsuro Ebashi to find the solution of the problem.

Golgi's contribution to medicine.

The historical analysis of Golgi's research work reveals that his contribution to the progress of science is not confined to neurosciences and to cellular biology. In fact, Golgi was a passionate and a skillful student of medical problems, in particular of those posed by infectious diseases. Golgi approached these problems with a rigorous method of observation and experimentation with the aim of understanding the genesis of the symptoms and their significance for the progress of the disease.

Defects in ordered aggregates of cardiolipin visualized by atomic force microscopy.

The formation and the nature of defects in ordered aggregates of cardiolipin (tetra acyl diphosphatidylglycerol) supported on solid substrates have been investigated by atomic force microscopy (AFM). The experiments were performed on two model systems, i.e.

Oxidative stress in fibroblasts from patients with pseudoxanthoma elasticum: possible role in the pathogenesis of clinical manifestations.

Pseudoxanthoma elasticum (PXE) is a genetic disease characterized by calcification and fragmentation of elastic fibres of the skin, cardiovascular system and eye, caused by mutations of the ABCC6 gene, which encodes the membrane transporter MRP6. The pathogenesis of the lesions is unknown. Based on studies of similar clinical and histopathological damage present in haemolytic disorders, our working hypothesis is that PXE lesions may result from chronic oxidative stress occurring in PXE cells as a consequence of MRP6 deficiency.

Use of the fluorescent dye 10-N-nonyl acridine orange in quantitative and location assays of cardiolipin: a study on different experimental models.

The fluorescent dye 10-N-nonyl acridine orange (NAO) is extensively used for location and quantitative assays of cardiolipin in living cells on the assumption of its high specificity for cardiolipin; however, the limits and the mechanism of this specificity are not clear. Moreover, whether factors such as the membrane potential in mitochondria may limit the consistency of the results obtained by this method is open to discussion. The aim of this research was to investigate the effects of some experimental factors on the selective fluorescence of NAO in the presence of cardiolipin in artificial and natural membranes (mitochondria).

The sarcoplasmic reticulum: its discovery and rediscovery.

In 1902, Emilio Veratti made the most accurate description, by light microscopy, of a reticular structure in the sarcoplasm. However, this structure was almost lost to man's knowledge for more than 50 years and was rediscovered during the 1960s, following the introduction of electron microscopy. Since then, biochemistry, electron microscopy and electrophysiology have unravelled the crucial role of the sarcoplasmic reticulum in the control of muscle contraction.

Lipid oxidation deletes the nanodomain organization of artificial membranes.

Nanoscopic domains with different crystal structures have been induced in closed artificial membranes and have been directly imaged by atomic force microscopy at a spatial resolution better than 0.3 nm. These observations provide experimental evidence to the hydrophobic mismatching theory of lateral phase separation phenomena.

Short-term hypothermia activates hepatic mitochondrial sn-glycerol-3-phosphate dehydrogenase and thermogenic systems.

The contribution of the sn-glycerol-3-phosphate (G-3-P) shuttle in the control of energy metabolism is well established. It is also known that its activity may be modulated by hormones involved in thermogenesis, such as thyroid hormones or dehydroepiandrosterone and its metabolites, that act by inducing de novo synthesis of mitochondrial G-3-P dehydrogenase (mGPDH). However, little is known as to the factors that may influence the activity without enzyme induction.

Zidovudine-induced experimental myopathy: dual mechanism of mitochondrial damage.

Myopathy often complicates Zidovudine (AZT) treatment in patients with acquired immunodeficiency syndrome (AIDS). The pathogenesis of the myopathy is controversial, since clinical phenomena intrinsic to AIDS may interfere per se with the onset of the myopathy. In the present work we investigated the in vivo effect of AZT in an animal model species (rat) not susceptible to HIV infection.

Effect of cardiolipin on functional properties of isolated rat liver mitochondria.

The specific involvement of cardiolipin in modulating and/or controlling the activity of a number of mitochondrial carriers, enzymes and receptors is well documented; however, comparatively less understood is its role for the integrated functions of intact mitochondria. The aim of the present research was to get a better insight into this problem by investigating the effect of in vitro addition of cardiolipin on the properties of isolated liver mitochondria. The results obtained show that cardiolipin induces extensive structural and functional perturbations at the level of the inner mitochondrial membrane.

Atomic force microscopy observations of acyl chains in phospholipids.

The potential use of atomic force microscopy (AFM) to image the mode of assembly and to measure the corresponding lattice parameters of model systems consisting of ordered aggregates of cardiolipin molecules has been investigated. An unprecedented resolution of about 0.2 nm has been achieved on suitably prepared specimens.

Comparative studies of effects of dehydroepiandrosterone on rat and chicken liver.

1. An attempt to identify the cause of decrease of gain in body weight during dehydroepiandrosterone (DHEA) treatment was made comparing the effects of hormone treatment on chickens and rats. 2.

Interaction of carnitine with mitochondrial cardiolipin.

The physiological role of L-carnitine is to determine the transport of acyl-CoA through the mitochondrial membrane. However, some observations may also suggest a direct effect of the molecule per se on the physical properties of the membrane, most probably at the level of the binding site. This possibility has been investigated by studying the influence of adriamycin, a drug that binds to cardiolipin, on the effect of carnitine on isolated rat liver mitochondria.

Mitochondrial inner membrane permeability changes induced by octadecadienoic acid hydroperoxide. Role of mitochondrial GSH pool.

The effect of exogenous octadecadienoic acid hydroperoxide (HPODE) on the functional properties of inner membrane of isolated rat liver mitochondria, as evaluated by the measurement of the membrane potential (delta psi) has been studied. Very low concentrations of HPODE (1.5-4.

Changes in liver structure and function after short-term and long-term treatment of rats with dehydroepiandrosterone.

The effects on the liver of feeding a diet containing 0.2% dehydroepiandrosterone were studied after short (7 d) and long (100 d) periods of treatment in rats. The short-term treatment caused hypertrophy of the hepatocytes that, at the ultrastructural level, seemed to be due to proliferation of peroxisomes and (to a minor extent) of mitochondria.

The protecting effect of L-carnitine on Ca(2+)-loaded rat liver mitochondria.

It is shown that L-carnitine strongly increases the ability of rat liver mitochondria to respond to the train of Ca2+ additions by a transient stimulation of the State-4 respiration rate. Such an effect requires ATP and the L-carnitine efficiency strongly decreases when ATP is omitted. Oleate influences the mitochondria in a fashion opposite to that of L-carnitine.

A 31P-NMR study on the energy state of rat liver in an experimental model of chronic dietary iron overload.

31P-NMR spectroscopy of rat liver perchloric acid extracts was utilized to assess the hepatic energy state in an experimental model of chronic dietary iron overload. Oral administration of iron for a period of 65 days that induces a steady ten-fold increase in hepatic iron concentration causes a significant decrease in the hepatic ATP level not associated with appreciable modifications of ADP and Pi levels. The phosphorylation ratio appears on the average decreased.

[The role of malate in regulating the rate of mitochondrial respiration in vitro].

Depletion of endogenous malate by preincubation of mitochondria at 30 degrees C in substrate-free media sharply decreases the rate of citrate oxidation and inhibits mitochondrial respiration in the presence of pyruvate and alpha-ketoglutarate. Addition of catalytic amounts of endogenous malate and its production via succinate oxidation promote rapid oxidation of citrate and pyruvate in the mitochondria and abolishes the lag period with alpha-ketoglutarate Malate increases the rate of membrane potential generation after addition of citrate, pyruvate or alpha-ketoglutarate to mitochondrial suspensions. Studies with controlled malate concentrations revealed that the changes in malate concentrations observed in the mitochondria in the presence of gluconeogenesis-inducing hormones may be due to the influence of these hormones on mitochondrial oxidation.

Early mitochondrial disfunction in bromobenzene treated mice: a possible factor of liver injury.

The membrane potential of liver mitochondria isolated from bromobenzene treated mice was studied. Specifically, the efficiency of the energy-transducing mitochondrial membrane was measured during the phase between the occurrence of a massive loss of hepatic GSH, after 2-3 hr of bromobenzene intoxication, and the appearance of lipid peroxidation and cell death (12-15 hr after treatment). Partial uncoupling of oxidative phosphorylation was observed in mitochondria during the early period of intoxication (3-9 hr).