Biomedical subjects

F Giorgi

Publications and source records attributed to F Giorgi.

At least 19 recordsLinked to original sources

PubMed2006

Identification of an isomer impurity in piperaquine drug substance.

A significant contaminant of the antimalarial drug piperaquine (1,3-bis-[4-(7-chloroquinolyl-4)-piperazinyl-1]propane) has been identified using liquid chromatography-mass spectrometry (LC-MS) and 2D NMR spectroscopy (1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC). The impurity was identified as the positional isomer 1-[(5-chloroquinolin-4)-piperazinyl]-3-[(7-chloroquinolin-4)-piperazinyl]propane. The impurity is formed because of contamination of batches of 4,7-dichloroquinoline (a precursor in the synthesis of piperaquine) with 4,5-dichloroquinoline. The amount of impurity (peak area impurity/peak area piperaquine using LC-UV at 347 nm) in old batches of piperaquine and in Artekin (the combination of dihydroartemisinin-piperaquine) ranged from 1.5 to 5%.

Antimalarials↗

PubMed2006

Extreme heat reduces and shifts United States premium wine production in the 21st century.

Premium wine production is limited to regions climatically conducive to growing grapes with balanced composition and varietal typicity. Three central climatic conditions are required: (i) adequate heat accumulation; (ii) low risk of severe frost damage; and (iii) the absence of extreme heat. Although wine production is possible in an extensive climatic range, the highest-quality wines require a delicate balance among these three conditions. Although historical and projected average temperature changes are known to influence global wine quality, the potential future response of wine-producing regions to spatially heterogeneous changes in extreme events is largely unknown. Here, by using a high-resolution regional climate model forced by the Intergovernmental Panel on Climate Change Special Report on Emission Scenarios A2 greenhouse gas emission scenario, we estimate that potential premium winegrape production area in the conterminous United States could decline by up to 81% by the late 21st century. While increases in heat accumulation will shift wine production to warmer climate varieties and/or lower-quality wines, and frost constraints will be reduced, increases in the frequency of extreme hot days (>35 degrees C) in the growing season are projected to eliminate winegrape production in many areas of the United States. Furthermore, grape and wine production will likely be restricted to a narrow West Coast region and the Northwest and Northeast, areas currently facing challenges related to excess moisture. Our results not only imply large changes for the premium wine industry, but also highlight the importance of incorporating fine-scale processes and extreme events in climate-change impact studies.

Agriculture↗

PubMed2006

Differential tissue expression of a calpastatin isoform in Xenopus embryos.

This study is aimed at demonstrating the role played by a calpastatin isoform (Xcalp3) in Xenopus embryos. A specific monoclonal antibody (mAb) was raised against a glutathione S-transferase (GST)-Xcalp3 fusion protein and characterized by immunoblotting and confocal fluorescence microscopy on stage 20-36 embryos. Under these conditions, calpastatin reactivity is associated with a major 110kDa protein fraction and preferentially expressed by notochord and somitic cells. In notochord cells, anti-calpastatin reactive sites were initially restricted to the luminal space of the vacuoles and later became diffused throughout the cytoplasm. In contrast, anti-calpastatin reactive sites in somitic cells were initially diffused throughout the cytoplasm and became restricted to a few intracellular granules in the later developmental stages. At the ultrastructural level, notochord cells appeared as flattened discs containing several vacuoles and numerous electron-dense granules. During transition from stages 26 to 32, electron-dense granules were gradually reduced in number as vacuoles enlarged in size and losed their calpastatin reactivity. Electron-dense granules were also present in myoblast cells and their number gradually reduced during development. To determine whether these observations bear any causal relationship to the calpain/calpastatin system, a number of Xenopus embryos were examined both ultrastructurally and histochemically following exposure to a specific calpain inhibitor (CI3). Under these conditions, Xenopus embryos exhibited an altered right-left symmetry and an abnormal axial shortening. In CI3-treated stage 32 embryos, notochord cells had a reduced vacuolar extension and exhibited at the same time an increase in granular content. The overall morphology of the somites was also distorted and myoblasts were altered both in shape and granular content. Based on these findings, it is concluded that the calpain/calpastatin may play an important role in the control of notochord elongation and somite differentiation during Xenopus embryogenesis.

Animals↗

PubMed2006

Viral particles of the endogenous retrovirus ZAM from Drosophila melanogaster use a pre-existing endosome/exosome pathway for transfer to the oocyte.

BACKGROUND: Retroviruses have evolved various mechanisms to optimize their transfer to new target cells via late endosomes. Here, we analyzed the transfer of ZAM, a retroelement from Drosophila melanogaster, from ovarian follicle cells to the oocyte at stage 9-10 of oogenesis, when an active yolk transfer is occurring between these two cell types. RESULTS: Combining genetic and microscopic approaches, we show that a functional secretory apparatus is required to tether ZAM to endosomal vesicles and to direct its transport to the apical side of follicle cells. There, ZAM egress requires an intact follicular epithelium communicating with the oocyte. When gap junctions are inhibited or yolk receptors mutated, ZAM particles fail to sort out the follicle cells. CONCLUSION: Overall, our results indicate that retrotransposons do not exclusively perform intracellular replication cycles but may usurp exosomal/endosomal traffic to be routed from one cell to another.

Animals↗

PubMed2006

P300-based brain computer interface: reliability and performance in healthy and paralysed participants.

OBJECTIVE: This study aimed to describe the use of the P300 event-related potential as a control signal in a brain computer interface (BCI) for healthy and paralysed participants. METHODS: The experimental device used the P300 wave to control the movement of an object on a graphical interface. Visual stimuli, consisting of four arrows (up, right, down, left) were randomly presented in peripheral positions on the screen. Participants were instructed to recognize only the arrow indicating a specific direction for an object to move. P300 epochs, synchronized with the stimulus, were analyzed on-line via Independent Component Analysis (ICA) with subsequent feature extraction and classification by using a neural network. RESULTS: We tested the reliability and the performance of the system in real-time. The system needed a short training period to allow task completion and reached good performance. Nonetheless, severely impaired patients had lower performance than healthy participants. CONCLUSIONS: The proposed system is effective for use with healthy participants, whereas further research is needed before it can be used with locked-in syndrome patients. SIGNIFICANCE: The P300-based BCI described can reliably control, in 'real time', the motion of a cursor on a graphical interface, and no time-consuming training is needed in order to test possible applications for motor-impaired patients.

Adult↗

PubMed2004

Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site.

The aim of this study was to assess the activity and toxicity of a platinum-based treatment on a group of patients with unknown primary tumours (UPTs). Patients with a diagnosis of UPT underwent a standard diagnostic procedure. Treatment was started within 2 weeks from diagnosis and consisted of carboplatin 400 mg m(-2) day 1, doxorubicin 50 mg m(-2) day 1, etoposide 100 mg m(-2) days 1-3, every 21 days. Response was evaluated after three courses and treatment continued in case of objective response (OR) or symptom control. A total of 102 patients were eligible. The median age was 59 years, sex male/female 54/48, histology was mainly adenocarcinoma or poorly differentiated carcinoma. Nodes, bone, liver and lung were the most frequently involved sites. In all, 79 patients received at least three courses of treatment; 26 patients received six courses or more. Six complete responses and 21 partial responses were observed, for a total of 27 of 102 ORs or 26.5% (95% confidence interval 18.2-36.1%). The median survival was 9 months and median progression-free survival was 4 months. Toxicity was moderate to severe, with 57.8% of patients experiencing grade III-IV haematological toxicity, mainly leucopenia. The regimen employed has shown activity in tumours of unknown primary site, but was associated with significant toxicity. Such toxicity may be considered unjustified, given the large proportion of patients with tumours not likely to respond. Efforts should therefore be addressed to identify predictors of response to chemotherapy, thus limiting aggressive treatment to those patients who could benefit from it.

Adult↗

PubMed2001

Reversible carnitine palmitoyltransferase inhibitors with broad chemical diversity as potential antidiabetic agents.

A series of carnitine related compounds of general formula XCH(2)CHZRCH(2)Y were evaluated as CPT I inhibitors in intact rat liver (L-CPT I) and heart mitochondria (M-CPT I). Derivative 27 (ZR = -HNSO(2)R, R = C(12), X = trimethylammonium, Y = carboxylate, (R) form) showed the highest activity (IC(50) = 0.7 microM) along with a good selectivity (M-CPT I/L-CPTI IC(50) ratio = 4.86). Diabetic db/db mice treated orally with 27 showed a significant reduction of serum glucose levels.

3-Hydroxybutyric Acid↗

PubMed2001

Cysteine proprotease colocalizes with vitellogenin in compound granules of the cockroach fat body.

A cysteine proprotease has been identified in developing embryos of the cockroach Blattella germanica and found to be a maternally encoded gene product that is transferred endocytically to the oocyte. The present study aims at establishing how this maternally derived proprotease is synthesized, packaged, and secreted during vitellogenesis. To this end, proprotease was localized immunocytochemically in the fat body of postmating females and its localization compared with that of vitellogenin over the same developmental periods. Fat bodies in cockroaches are comprised of two different cell types: trophocytes and bacteriocytes. Data show that proprotease and vitellogenin come to colocalize in compound granules of the fat body trophocytes. While synthesis of vitellogenin can be traced back to granules resulting from the coalescence of Golgi-derived vesicles in the trophocyte cytoplasm, proprotease appears to be localized predominantly on the cytolysosomes of both trophocytes and bacteriocytes. When probed with an anti-proprotease antiserum, bacteria are also positively labeled, regardless of whether they are segregated inside the cytolysosomes or free in the bacteriocyte cytoplasm. Since vitellogenin and proprotease colocalize within the same cell organelle, it is assumed that Golgi-derived vesicles, which contain vitellogenin, may fuse with cytolysosomes bearing proprotease to yield compound secretory granules. To account for the present observations, the origin and role of proprotease are discussed in relation to the turnover of bacteria in the fat body and to the requirements of endosymbiosis.

Animals↗

PubMed2001

Yolk granules are differentially acidified during embryo development in the stick insect Carausius morosus.

Newly laid eggs of stick insects comprise a unique fluid ooplasm that is gradually partitioned into a number of yolk granules by invasion of secondary vitellophages. This study aimed at establishing how yolk granules become acidified in the course of embryonic development. Data show that acidified yolk granules are rather scarce and randomly distributed in vitellophages of early embryos, while they tend to increase gradually in number as development proceeds to completion. Yolk granule acidification is progressively more inhibited in the presence of increasing concentrations of chloroquine, monensin and bafilomycin. A pro-protease was identified cytochemically and by immunoblotting in yolk extracts of progressively more advanced embryos. A specific monoclonal antibody raised against this pro-protease helped to demonstrate that it is gradually processed to yield a lower molecular weight polypeptide as development proceeds to completion. This latter polypeptide was identified as a protease using electrophoresis in polyacrylamide gels containing yolk extracts. Simultaneous administration of a fluorescent substrate for cysteine protease and an acidotropic probe produced superimposable labelling patterns, suggesting that only acidified yolk granules possess a proteolytic activity. On the other hand, yolk granules probed simultaneously for acidification and latent pro-protease yielded labelling patterns partially superimposed. Pro-protease labelling is gradually lost as yolk granules are progressively more acidified during development. Distinct labelling patterns were also obtained in vitellophages processed for the simultaneous detection of pro-protease and protease, suggesting that the two activities are expressed by different yolk granule populations, and that one is gradually converted into the other as time goes by.

Acids↗

PubMed2001

Serosa membrane plays a key role in transferring vitellin polypeptides to the perivitelline fluid in insect embryos.

In mid-embryogenesis, the stick insect Carausius morosus comes to be comprised of three distinct districts: the embryo proper, the yolk sac and the perivitelline fluid. A monolayered epithelium, the so-called serosa membrane, encloses the yolk sac and its content of vitellophages and large yolk granules. During embryonic development, the yolk sac declines gradually in protein concentration due to Vt polypeptides undergoing limited proteolysis to yield a number of Vt cleavage products of lower molecular weights. mAbs 1D1 and 5H11 are monoclonal antibodies raised against some of the Vt cleavage products generated by this process in the yolk sac. At the confocal microscope, antibody fluorescence is initially associated with a few yolk granules, while it is gradually displaced in the cytosolic spaces of the vitellophages. With the proceeding of embryonic development, label appears also in the serosa membrane in the form of clustered dots. At the ultrastructural level, gold particles are initially associated with the vitellophages that are labeled on a few yolk granules and in the cytosolic space flanking the yolk granules. Subsequently, the serosa cells become labeled on vesicles close to the yolk granules or just underneath the plasma membrane. Inside the serosa cells, label is also associated with granules budding from the Golgi apparatus, but never with the intercellular channels percolating the serosa membrane. These observations are interpreted as indicating that Vt cleavage products leak out from the yolk granules into the cytosolic spaces of the vitellophages and are eventually transferred to the perivitelline fluid via transcytosis through the serosa cells.

Animals↗

PubMed2001

Yolk utilization in stick insects entails the release of vitellin polypeptides into the perivitelline fluid.

This study investigates the developmental fate of vitellin (Vt) polypeptides generated by limited proteolysis in an insect embryo. To this end, a number of polyclonal (pAb) and monoclonal antibodies (mAb) were raised against the yolk sac and the perivitelline fluid of late embryos of the stick insect Carausius morosus. Two dimensional immuno gel electrophoresis and Western blotting demonstrate that polypeptides resulting from Vt processing are present both in the yolk sac and the perivitelline fluid. At the confocal microscope, different labelling patterns were detected in the ooplasm depending on the stage of development attained by the embryo. At early developmental stages, label is associated with large unsegmented portions of the fluid ooplasm. During embryonic development, the fluid ooplasm is gradually transformed into yolk granules by intervention of vitellophages. Prior to dorsal closure, the yolk sac is separated from the perivitelline fluid by interposition of serosa cells (the so called serosa membrane). Several mAbs raised against the perivitelline fluid react specifically with this membrane suggesting that the release of Vt polypeptides from the yolk sac occurs by intracellular transit through the serosa cells. By immunocytochemistry, gold label appears associated with the cell surface and a number of vacuoles of the serosa membrane. These data are interpreted as suggesting that Vt polypeptides resulting from limited proteolysis in stick insect embryos are not exhaustively degraded within the yolk sac, but are instead transferred transcytotically to the perivitelline fluid through the serosa membrane.

Animals↗

PubMed2000

Deriving a quantitative chirality measure from molecular similarity indices.

A versatile new method has been developed as a continuous symmetry measure for chiral compounds. The application of principal component analysis (PCA) to the complete N x N pairwise similarity matrices (electrostatic potential and shape indices) of a series of dihydropyridine calcium channel antagonists allowed to single out a chirality component and to compute a chirality score in terms of the between-enantiomers difference on the component value. The possibility to have chirality defined continuously at the series level could be of importance in eudismic analyses where the relative potency of two enantiomers is studied as well as in QSAR studies dealing with chiral molecules in order to improve the power of the generated models.

Calcium Channel Blockers↗

PubMed2000

Life cycle of an endogenous retrovirus, ZAM, in Drosophila melanogaster.

ZAM is an env-containing member of the gypsy family of retrotransposons that represents a possible retrovirus of invertebrates. In this paper, we traced ZAM mobilization to get information about a potential path a retroelement may take to reach the germ line of its host. In situ hybridization on whole-mount tissues and immunocytochemistry analyses with antibodies raised against ZAM Gag and Env proteins have shown that all components necessary to assemble ZAM viral particles, i.e., ZAM full-length RNAs and Gag and Env polypeptides, are coexpressed in a small set of follicle cells surrounding the oocyte. By electron microscopy, we have shown that ZAM viral particles are indeed detected in this somatic lineage of cells, which they leave and enter the closely apposed oocyte. Our data provide evidence that the vesicular traffic and yolk granules in the process of vitellogenesis play an important role in ZAM transfer to the oocyte. Our data support the possibility that vitellogenin transfer to the oocyte may help a retroelement pass to the germ line with no need of its envelope product.

Animals↗

PubMed1999

Case study of the effects of atmospheric aerosols and regional haze on agriculture: an opportunity to enhance crop yields in China through emission controls?

The effect of atmospheric aerosols and regional haze from air pollution on the yields of rice and winter wheat grown in China is assessed. The assessment is based on estimates of aerosol optical depths over China, the effect of these optical depths on the solar irradiance reaching the earth's surface, and the response of rice and winter wheat grown in Nanjing to the change in solar irradiance. Two sets of aerosol optical depths are presented: one based on a coupled, regional climate/air quality model simulation and the other inferred from solar radiation measurements made over a 12-year period at meteorological stations in China. The model-estimated optical depths are significantly smaller than those derived from observations, perhaps because of errors in one or both sets of optical depths or because the data from the meteorological stations has been affected by local pollution. Radiative transfer calculations using the smaller, model-estimated aerosol optical depths indicate that the so-called "direct effect" of regional haze results in an approximately 5-30% reduction in the solar irradiance reaching some of China's most productive agricultural regions. Crop-response model simulations suggest an approximately 1:1 relationship between a percentage increase (decrease) in total surface solar irradiance and a percentage increase (decrease) in the yields of rice and wheat. Collectively, these calculations suggest that regional haze in China is currently depressing optimal yields of approximately 70% of the crops grown in China by at least 5-30%. Reducing the severity of regional haze in China through air pollution control could potentially result in a significant increase in crop yields and help the nation meet its growing food demands in the coming decades.

Agriculture↗

PubMed1998

L-carnitine esters as "soft", broad-spectrum antimicrobial amphiphiles.

A new class of antimicrobial, "soft", quaternary ammonium l-carnitine esters, of the type (CH3)3N+-CH2-CHOCO(R1)-CH2-COO(R2) Cl-, has been designed, with R1 and R2 being in general long-chain alkyl substituents. The series shows good activity against a wide range of bacteria, yeasts, and fungi. Lipophilicity has been measured by RP-HPLC method to give the logarithm of the experimental capacity factor (log k'), and a quantitative relationship has been determined between log k' and the theoretical partition coefficient (CLOGP); also, bond-dipole descriptors have been introduced into calculations by accounting for polar moieties present within the apolar cores of the molecules, giving a more refined calculated capacity factor (log k'calcd). Finally the latter has been related to the antimicrobial activity (MIC values). The proposed models are predictive for the best broad-spectrum antimicrobial compound within the series.

Anti-Bacterial Agents↗

PubMed1998

QSAR models for discriminating between mutagenic and nonmutagenic aromatic and heteroaromatic amines.

In a previous article, we demonstrated that the structure-activity relationship model for the mutagenic potency of aromatic amines is different from that for discriminating between mutagens and nonmutagens. In this work, we present further analyses on the molecular determinants of the mutagenicity of aromatic amines. Based on the use of various methodological approaches, our results indicate that mutagenic activity is influenced by different molecular characteristics in different subclasses of aromatic amines. Thus, the general lesson of this article is that 1) in genetic toxicology, it is necessary to separately investigate the structure-activity relationships for discrimination between positive and negative chemicals, and the structure-activity relationships for the potency of the positive chemicals; 2) in structure-activity studies, it is necessary to investigate the degree of homogeneity (congenericity) of apparently similar chemicals in order to assess and describe the various mechanisms of action that may be elicited by the chemicals.

Amines↗

PubMed1998

Confocal scanning laser microscopy of the follicular epithelium in ovarioles of the stick insect Carausius morosus.

Ovarian follicles of the stick insect Carausius morosus were analyzed by confocal laser microscopy and immunocytochemistry with a view to studying cell polarity in the follicular epithelium. Such probes as anti-alpha-tubulin antibodies and Rh-phalloidin were employed to establish how the follicle cell cytoskeleton changes during ovarian development. Data show that alpha-tubulin prevails over the basal end, while F-actin appears more abundant along the apical end of the follicle cells. This finding was further corroborated by immunogold cytochemistry, showing that label along the basal end is primarily associated with microtubules, while that along the apical end is due to follicle cell microvilli interdigitating with the oocyte plasma membrane. A monoclonal antibody specifically raised against a vitellin polypeptide was used to investigate the role the follicular epithelium might play in relation to vitellogenin (Vg) uptake by the oocyte. Data show that under these conditions label is restricted to the intercellular channels of the follicular epithelium, thus providing further support to the notion that Vg enters the oocyte through the extracellular pathway leading from the basement lamina to the oocyte surface. By contrast, the use of a monoclonal antibody raised against a fat-body-derived protein of 85 kDa that is specifically sulfated within the follicle cells provides evidence for the existence of an alternative way of gaining access to the oocyte surface, that is by transcytosis through the follicular cell epithelium. These findings confirm our earlier observations on stick insect ovarioles whereby polarization in the follicular epithelium is primarily addressed to sustain a transcytotic vesicular traffic between opposite poles of the follicle cell of Vg toward the oocyte surface.

Animals↗

PubMed1998

A fat body derived protein is selectively sulfated in the stick insect ovary by transcytosis through the follicular epithelium.

With the onset of vitellogenesis, the follicular epithelium overlying the oocyte in stick insect ovarioles becomes highly polarized and patent by formation of wide intercellular spaces. The aim of the present study was to provide experimental support to the notion that the follicular epithelium in this insect species may be involved in transcytosis. Data demonstrate that the follicular epithelium carries out sulfo-conjugation of a 85 kDa fat body derived protein by allowing it ot transit from one cell pole to another. Along the basal end, follicle cells branch into a number of cytoplasmic finger-like projections. At the opposite end facing the oocyte they taper off into lance-head shapes. Different vesicular elements are evident at both these extremities. In vivo exposure to horseradish peroxidase shows that the vesicular elements present along the apical end provide an endocytic entry. In contrast, those present along the basal end are labeled with sodium [35S]-sulfate, suggesting that they may be exocytic vesicles containing a sulfo-conjugated secretory product. In vivo exposure to sodium [35S]-sulfate caused radioactivity to appear over the Golgi apparatus and some nearby vesicles of the follicle cell cytoplasm, including the exocytic vesicles. The intracellular pathway of the follicle cells was also examined by immunogold labeling using a monoclonal antibody raised against a 85 kDa fat body derived protein. Under these conditions, gold particles were consistently detected over the Golgi apparatus and the vesicular elements lying along both poles of the follicle cell membrane. Based on this evidence, it is concluded that follicular cells in stick insect ovarioles are endowed with the ability to undergo transcytosis by providing an endocytic entry along the apical end and by releasing exocytically a sulfo-conjugated 85 kDa protein along the baso-lateral domain of the follicle cell membrane.

Animals↗