High DeltaN p63 isoform expression favours recurrences in odontogenic keratocyst--odontogenic keratocystic tumour.
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Adolescent↗
Biomedical subjects
G Marucci
Publications and source records attributed to G Marucci.
Antiviral properties of deazaadenine nucleoside derivatives.
Viral infections have menaced human beings since time immemorial, and even today new viral strains that cause lethal diseases are being discovered with alarming frequency. One major example is HIV, the etiological agent of AIDS, which spread up in the last two decades. Very recently, other virus based diseases such as avian flu have spread fear around the world, and hemorrhagic fevers from central Africa serious threaten human health because of their very deadly effects. New antiviral agents are still greatly needed to counter these menaces. Many scientists are involved in this field of research, and many of the recently discovered effective antiviral compounds are nucleoside analogues. Among those derivatives, deazapurine nucleoside analogues have demonstrated potent inhibitory effect of viral replication. This review reports on recently generated data from preparing and testing deazapurine nucleoside derivatives as inhibitors in virus replication systems. Although most of the reported data have been produced in antiHIV, antiHCMV, and antiHSV biological testing, very recently other new important fields of application have been discovered, all in topical subjects of strong interest. In fact, deazapurine nucleosides have been found to be active as chemotherapeutics for some veterinary systemic viral infections, for which no antiviral drugs are licensed yet. Furthermore, they demonstrated efficacy in the inhibition of Hepatitis C virus replication. Finally, these compounds showed high potency as virucides against Ebola Virus, curing Ebola infected mice with a single dose administration.
Animals↗
[Mature cystic teratoma of the ovary with a small ganglioneuroma].
A case of ganglioneuroma arising within a cystic mature teratoma of the ovary in a 34-year-old woman is reported. Patient underwent right adnexectomy. The ovary was completely replaced by a bilocular cystic lesion, measuring 8 cm in diameter and filled with adipose tissue and pilosebaceous material. Microscopically the cyst was composed by a mature cystic teratoma containing skin with dermal appendages, fatty tissue and bronchial epithelium. Furthermore a nodule (0.5 cm in size) composed of mature ganglion cells, axons and Schwann cells, was identified. Ganglion cells were positive for NSE and synaptophysin, while Schwann cells stained positively with S100 protein and GFAP. To the best of our knowledgment this is the first reported cases of ganglioneuroma arisen within a cystic mature teratoma of the ovary.
Adult↗
Trichinella britovi etiological agent of sylvatic trichinellosis in the Republic of Guinea (West Africa) and a re-evaluation of geographical distribution for encapsulated species in Africa.
In West Africa, Trichinella infection was documented in humans and animals from Senegal in the 1960s, and the biological characters of one isolate showed a lower infectivity to domestic pigs and rodents when compared with that of a Trichinella spiralis pig isolate from Europe. To identify the Trichinella species present in West Africa, a survey was conducted in a total of 160 wild animals in the Republic of Guinea. Three Viverridae, one true civet (Viverra civetta) and two African palm civets (Nandinia binotata) from the Fouta Djallon Massif, Pilimini Subprefecture, were found positive by artificial digestion of muscle samples. Trichinella larvae from these three viverrids were identified as Trichinella britovi and no difference was detected in three examined sequences from these African isolates and the reference strain of T. britovi from Europe, indicating common ancestry, an historically continuous geographic distribution, and recent isolation for African and European populations. The detection of T. britovi in West Africa modifies our knowledge about the distribution of encapsulated species of Trichinella in Africa. Thus, Trichinella nelsoni is now considered to have a distribution limited to the Eastern part of the Afrotropical region from Kenya to South Africa. This provides a plausible explanation for the presence of Trichinella T8 in Namibia and South Africa, and further suggests that T. britovi could be the Trichinella species circulating among wild animals of Northern Africa.
Animals↗
Peripheral ameloblastoma with Merkel cells.
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Ameloblastoma↗
Trichinella pseudospiralis foci in Sweden.
In Sweden, the prevalence of Trichinella infection in domestic pigs has greatly decreased since the 1970s, with no reports in the past 4 years. However, infected wild animals continue to be found. The objective of the present study was to identify the species of Trichinella present in animals of Sweden, so as to contribute to the knowledge on the distribution area and hosts useful for the prevention and control of this zoonosis. In the period 1985-2003, Trichinella larvae were detected in the muscles of 81/1800 (4.5%) red foxes (Vulpes vulpes), 1/6 (16.7%) arctic fox (Alopex lagopus), 1/7 (14.3%) wolf (Canis lupus), 10/200 (5.0%) lynxes (Lynx lynx), 4/8000 (0.05%) wild boars (Sus scrofa), and 27/66 x 10(6) (0.000041%) domestic pigs. All four Trichinella species previously found in Europe were detected (Trichinella spiralis, T. nativa, T. britovi and T. pseudospiralis). The non-encapsulated species T. pseudospiralis was detected in three wild boars from Holo (Stockholm area) and in one lynx from Froso (Ostersund area), suggesting that this species is widespread in Sweden. These findings are consistent with those of a study from Finland, both for the unexpected presence of T. pseudospiralis infection and the presence of the same four Trichinella species, suggesting that this epidemiological situation is present in the entire Scandinavian region. The widespread diffusion of T. pseudospiralis in the Scandinavian region is also important in terms of it potential impact on public health, given that human infection can occur and the difficulties to detect it by the trichinelloscopic examination.
Animals↗
Trichinella papuae and Trichinella zimbabwensis induce infection in experimentally infected varans, caimans, pythons and turtles.
The discovery of Trichinella zimbabwensis in farm crocodiles of Zimbabwe has opened up a new frontier in the epidemiology of the Trichinella genus. The objective of the present study was to investigate the infectivity of encapsulated species (T. spiralis, T. nativa, T. britovi, T. murrelli and T. nelsoni) and non-encapsulated species (T. pseudospiralis, T. papuae and T. zimbabwensis) in caimans (Caiman crocodilus), varans (Varanus exanthematicus), pythons (Python molurus bivittatus) and turtles (Pelomedusa subrufa) raised at their natural temperature range (26-32 degrees C). Mice and chickens were used as controls. At 6 days post-infection (p.i.), adult worms were detected in the small intestine of reptiles infected with T. papuae and T. zimbabwensis, of chickens infected with T. pseudospiralis and of mice infected with all encapsulated and non-encapsulated species. At 60 days p.i., T. papuae and T. zimbabwensis adult worms were collected from the intestine of varans and caimans and larvae from muscles of the four reptile species, T. pseudospiralis larvae from muscles of chickens, and larvae of all Trichinella species from mouse muscles. The highest reproductive capacity index of both T. papuae and T. zimbabwensis was observed in varans. The results show that T. papuae and T. zimbabwensis are able to complete their entire life-cycle in both poikilothermic and homoiothermic animals.
Animals↗
Extraintestinal nematode infections of red foxes (Vulpes vulpes) in Hungary.
A survey was carried out to investigate the prevalence and worm burden of extraintestinal nematodes in 100 red foxes (Vulpes vulpes) of Hungary. The overall prevalence of nematode infections of the respiratory tract was 76%. Eucoleus aerophilus (Capillaria aerophila) was the predominant species (66%), followed by Crenosoma vulpis (24%), Eucoleus (Capillaria) böhmi (8%) and Angiostrongylus vasorum (5%). Pearsonema (Capillaria) plica was found in 52% of the urinary bladders. In 3% of the foxes, Trichinella britovi was present in muscle samples. The high prevalence of lungworms and P. plica and the fox colonisation in urban areas may enhance the prevalence of these nematode infections in domestic dogs and cats, and the flow of T. britovi from the sylvatic cycle to the domestic cycle, enhancing the risk of infections in humans.
Animals↗
Searching for cyclazosin analogues as alpha(1B)-adrenoceptor antagonists.
A series of quinazoline derivatives, 2-20, structurally related to the racemic alpha(1)-adrenoceptor antagonist cyclazosin (1), were synthesized and evaluated for their functional antagonism at alpha(1)- and alpha(2)-adrenoceptors and for their binding affinity at human cloned alpha(1a)-, alpha(1b)- and alpha(1d)-adrenoceptor subtypes. They displayed, like 1, preferential antagonism and selectivity for alpha(1) versus alpha(2)-adrenoceptors. Compounds 10, 13, and 18 showed high potency at alpha(1)-adrenoceptors similar to that of 1 (pK(B) values 8.47-8.89 versus 8.67), whereas 13 and 15 were endowed with the highest alpha(1)-adrenoceptor selectivity, only 3- to 4-fold lower than that of 1. In binding experiments, all of the compounds displayed an affinity practically similar to that found for 1, with the exception of 19 and 20 that were definitely less potent. The s-triazine analogue 18 was the most potent of the series with pK(i) values of 10.15 (alpha(1a)), 10.22 (alpha(1b)) and 10.40 (alpha(1d)), resulting 77-fold more potent than 1 at alpha(1a)-adrenoceptors. In addition, the majority of compounds, like prototype 1, showed the same trend of preferential affinity for alpha(1d)- and alpha(1b)-adrenoceptors that alpha(1a)-subtype. In conclusion, we identified compounds 2-5, 10, 12 and 13, bearing either an aliphatic- or an arylalkyl- or aryloxyalkyl-acyl function, with an interesting subtype-selectivity profile, which makes them suitable candidates for their resolution as enantiomers structurally related to (+)-cyclazosin.
Adrenergic alpha-1 Receptor Antagonists↗
Molecular identification of natural hybrids between Trichinella nativa and Trichinella T6 provides evidence of gene flow and ongoing genetic divergence.
To date, there are no data available on the population genetics of Trichinella due to the lack of genetic markers and the difficulty of working with such small parasites. In the Arctic region of North America and along the Rocky Mountains, there exist two genotypes of Trichinella, Trichinella nativa and Trichinella T6, respectively, which are well differentiated by biochemical and molecular characters. However, both are resistant to freezing, show other common biological characters (e.g. low or no infectivity to rodents and swine) and produce fertile F1 offspring upon interbreeding. To data, these two genotypes have been considered allopatric. In this study, we detected both genotypes in wolves of the same wolf packs in Alaska, suggesting sympatry. A single GTT trinucleotide present in the ITS-2 sequence of T. nativa but not in Trichinella T6 was used as a genetic marker to study gene flow for this character in both a murine infection model and in larvae from naturally-infected Alaskan wolves. Only F1 larvae originating from a cross between T. nativa male and Trichinella T6 female were able to produce F2 offspring. Larvae (F1) originating from a cross between Trichinella T6 male and T. nativa female were not reproductively viable. As expected, all F1 larvae showed a heterozygote pattern for the GTT character upon heteroduplex analysis; however, within the F2 population, the number of observed heterozygotes (n=52) was substantially higher than expected (n=39.08), as supported by the F(is) index, and was not in the Hardy-Weinberg equilibrium. Larvae from two of the 16 Trichinella positive Alaskan wolves, showed the Trichinella T6 pattern or the T. nativa/Trichinella T6 hybrid pattern. Our data demonstrate that T. nativa and Trichinella T6 live in sympatry at least in Alaskan wolves, where T. nativa occurs more frequently (69%) than Trichinella T6 (31%). One explanation for this phenomenon is that glacial periods may have caused a geographical relocation, colonisation and independent evolution of T. nativa within the Rocky Mountains, resulting in a bifurcation of the freeze-resistant genotype. Additional studies will be required to test this hypothesis.
Alaska↗
Fibrinogen storage disease without hypofibrinogenaemia associated with acute infection.
AIMS: The presence of ground glass hepatocytes in a liver biopsy may be related to different conditions, including fibrinogen storage disease. Three types of fibrinogen storage disease have been described, namely types I, II and III. Type I is an hereditary hypofibrinogenaemia genetically characterized by a mutant variant of the fibrinogen molecule designated as fibrinogen Brescia, consistent with a gamma284 Gly-->Arg mutation. Only rare cases of types II and III fibrinogen storage disease have been described. The purpose of the present paper is to describe two cases of fibrinogen storage disease without associated hypofibrinogenaemia, which appeared during acute infectious diseases. METHODS AND RESULTS: Both patients were female, aged 77 and 73 years, who developed high transaminases during an infectious disease. In each case blood coagulation tests were within the normal range, and despite clinical and laboratory investigations no possible cause for liver disease could be found. Liver biopsies were performed; in both cases weakly eosinophilic cytoplasmic inclusions were observed. Using immunohistochemistry the inclusions were found to be due to fibrinogen accumulation. At ultrastructural level features corresponding to type II inclusions were observed. Molecular studies, performed in case 2, excluded the mutation typical of type I fibrinogen storage disease. Both patients also presented features of chronic hepatitis. In case 1, giant cell granulomas were additionally present. No close relatives of the patients presented any clinical or laboratory features of liver disease. In both patients altered liver function test values gradually, spontaneously, returned to within normal ranges after infectious disease was resolved. CONCLUSIONS: These cases suggest that, on rare occasions, hepatocytes may accumulate fibrinogen during an infectious disease.
Acute Disease↗
Trichinella zimbabwensis n.sp. (Nematoda), a new non-encapsulated species from crocodiles (Crocodylus niloticus) in Zimbabwe also infecting mammals.
Since 1995, Trichinella larvae have been detected in 39.5% of farmed crocodiles (Crocodylus niloticus) in Zimbabwe. Morphological, biological, biochemical and molecular studies carried out on one isolate from a farmed crocodile in 2001 support the conclusion that this parasite belongs to a new species, which has been named Trichinella zimbabwensis n.sp. This species, whose larvae are non-encapsulated in host muscles, infects both reptiles and mammals. The morphology of adults and larvae is similar to that of Trichinella papuae. Adults of T. zimbabwensis cross in both directions with adults of T. papuae (i.e. male of T. zimbabwensis per female of T. papuae and male of T. papuae per female of T. zimbabwensis), producing F1 offspring which produce very few and less viable F2 larvae. Muscle larvae of T. zimbabwensis, like those of T. papuae, do not infect birds. Three allozymes (of a total of 10) are diagnostic between T. zimbabwensis and T. papuae, and five are diagnostic between T. zimbabwensis and Trichinella pseudospiralis, the third non-encapsulated species. The percentage of the pairwise alignment identity between T. zimbabwensis and the other Trichinella species for the cytochrome oxidase subunit I gene, the large subunit ribosomal-DNA (mt-lsrDNA) gene and the expansion segment five, shows that T. zimbabwensis is more similar to the two non-encapsulated species T. papuae (91% for cytochrome oxidase I; 96% for mt-lsrDNA; and 88% for expansion segment five) and T. pseudospiralis (88% for cytochrome oxidase I; 90% for mt-lsrDNA; and 66-73% for expansion segment five) than to any of the encapsulated species (85-86% for cytochrome oxidase I; 88-89% for mt-lsrDNA; and 71-79% for expansion segment five). This is the first non-encapsulated species discovered in Africa. The finding of a new Trichinella species that infects both reptiles and mammals suggests that the origin of Trichinella parasites dates back further than previously believed and can contribute to understanding the phylogeny and the epidemiology of the genus Trichinella.
Alligators and Crocodiles↗
Analogues of prazosin that bear a benextramine-related polyamine backbone exhibit different antagonism toward alpha1-adrenoreceptor subtypes.
Hybrid tetraaamine disulfides 4-9 were synthesized by combining the structural features of prazosin (1), a competitive alpha1-adrenoreceptor antagonist, and benextramine (2), an irreversible alpha1/alpha2-adrenoreceptor antagonist, and their biological profiles at alpha1-adrenoreceptor subtypes were assessed by functional experiments in isolated rat vas deferens (alpha1A), spleen (alpha1B), and aorta (alpha1D). To verify the role of the disulfide moiety on the interaction with alpha1-adrenoreceptor subtypes, carbon analogues 10-15 were included in this study. All quinazolines lacking the disulfide bridge behaved, like 1, as competitive antagonists, whereas all polyamine disulfides displayed a nonhomogeneous mechanism of inhibition at the three subtypes since they were, like 2, noncompetitive antagonists at the alpha1A and alpha1B subtypes while being, unlike 2, competitive antagonists at the alpha1D. In particular, the blocking effects were characterized by a decrease of the maximal response to noradrenaline that was affected only slightly by washings. Probably the alpha1A and alpha1B subtypes bear in the binding pocket a suitable thiol function that would suffer an interchange reaction with the disulfide moiety of the antagonist and which is missing, or not accessible, in the alpha1D subtype. Polyamines 8, 9, and 14, among others, emerged as promising tools for the characterization of alpha1-adrenoreceptors, owing to their receptor subtype selectivity. Finally, the effect of nonbasic substituents on the phenyl ring of prazosin analogues 16-28 on potency and selectivity for the different subtypes can hardly be rationalized.
Adrenergic alpha-Antagonists↗
Synthesis, absolute configuration and antimuscarinic activity of the enantiomers of [1-(2,2-diphenyl-[1,3]dioxolan-4-yl)-ethyl]-dimethyl-amine.
Methylation of the carbon atom C of compound 1, a potent and not selective muscarinic antagonist, was carried out. The resulting diastereomers were separated and the corresponding racemate further resolved to give four enantiomers, which were tested both as hydrogen oxalate and methiodide salts. The pharmacological results obtained at M1, M2 and M3 muscarinic receptor subtypes, show that methylation at C1, depending on the stereochemistry, increases antagonist potency, having thus the same effect of nitrogen quaternization. These results may well lead to the development of new potent antimuscarinic drugs lacking a cationic head.
Animals↗
Trichinella pseudospiralis populations of the Palearctic region and their relationship with populations of the Nearctic and Australian regions.
Since few non-encapsulated isolates of Trichinella have been studied to date, their level of differentiation from encapsulated species and the taxonomic value of the observed polymorphisms remain to be determined. To this end, biological, biochemical and molecular data from 11 isolates of Trichinella pseudospiralis and one isolate of Trichinella papuae were examined using the broad group of encapsulated species and genotypes for comparison. Single-worm cross-breeding experiments and reproductivity capacity indices revealed F1 progeny only among T. pseudospiralis isolates from different zoogeographical regions, whereas no F1 were produced when T. pseudospiralis was crossed with T. papuae. Furthermore, unlike T. pseudospiralis, T. papuae failed to infect chickens. Comparative analysis of 12 allozymes revealed a single difference between Nearctic and Australian isolates of T. pseudospiralis, but substantial differences when compared with T. papuae (i.e. two unique and six diagnostic markers). Molecular studies involving mitochondrial-derived genes encoding cytochrome oxidase I and the large subunit ribosomal DNA indicated a high level of sequence similarity among T. pseudospiralis isolates; however, a concomitantly high level of variation was observed in expansion segment five of the genomic large subunit ribosomal DNAs among T. pseudospiralis isolates and between this species and T. papuae. Collectively, these results demonstrate high uniformity among isolates of T. pseudospiralis from Eurasia and polymorphism among isolates of T. pseudospiralis belonging to different zoogeographical regions; the results corroborate the classification of T. papuae as a differentiated species.
Animals↗
Structure-activity relationships in 2,2-diphenyl-2-ethylthioacetic acid esters: unexpected agonistic activity in a series of muscarinic antagonists.
As a continuation of previous research on anticholinergic drugs derived from 2,2-diphenyl-2-ethylthioacetic acid, several 5,5-diphenyl-5-ethylthio-2-pentynamines (2-11) were synthetised and their antimuscarinic activity on M(1-4) receptor subtypes was evaluated by functional tests and binding experiments. One of the compounds obtained showed unexpected agonistic activity in functional experiments on M(2) receptors. Since the compound carried a phenylpiperazine moiety, other similar compounds (12-17) were prepared and found to be endowed with similar behaviour. These ligands, although possessing the bulky structure characterising muscarinic antagonists, display agonistic activity at M(2) subtypes while, as expected, behaving as antagonists on M(3) and M(4) subtypes. On M(1) subtypes, they show agonistic activity which, however, is not blocked by atropine. The peculiar pharmacological profile of these compounds is of interest for studying muscarinic receptor subtypes.
Alkynes↗
Gemcitabine-associated CD8+ CD30+ pseudolymphoma.
We describe a 69-year-old man with a non-small cell carcinoma of the lung, stage III B, who developed bilateral multiple erythematous lesions in the abdominal-inguinal area following treatment with gemcitabine. Histologically, the lesion was characterized by a heavy lymphocytic infiltrate with large CD30+ cells. The lesion was highly suggestive of cutaneous involvement by malignant lymphoma, but complete regression was observed after cessation of gemcitabine. Although rarely reported, gemcitabine therapy can induce skin lesions. Pathologists should be aware of this possibility in order to avoid a misdiagnosis.
Aged↗
Hunting practices increase the prevalence of Trichinella infection in wolves from European Russia.
From 1998 to 2000, 184 animals (82 wolves, 29 red foxes, 55 mustelids, 5 raccoon dogs, and 13 domestic dogs), mainly shot by hunters in the Tvier and Smoliensk regions of northwest European Russia, were tested for Trichinella larvae; 98 animals (53.3%) were found to be positive. The highest prevalence was detected in wolf (97.5%). Trichinella nativa was the most common species detected (98%). The diet of wolves was investigated by examining the stomach contents of 62 animals (75.6% of the total number of wolves examined for Trichinella). It consisted mainly of dog (36.4% of the total number of occurrences of all food items, PFO) and moose (31.2 PFO); however, during the hunting seasons of 1998-1999 and 1999-2000, skinned wolf carcasses were left in the forest as bait (567 carcasses, about 18,000 kg). This very high prevalence of Trichinella infection, the highest ever detected in a natural population of carnivores, could be explained by carnivore-carnivore transmission, influenced by the hunting practices adopted in the study area.
Animals↗