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.
The aim of this study was to evaluate the inflammatory response in the muscle tissue against Trichinella larvae of encapsulated (T. spiralis, T. britovi) and non-encapsulated (T. pseudospiralis) ...species. The inflammatory response was estimated in histological sections of muscle tissues from Trichinella-infected CD1 mice by a newly developed method. Nuclei were stained with one fluorescent probe, which binds nucleic acids with high affinity, and fluorescence was analysed by a software program. Evaluation of the relative fluorescence units was performed in both peri-capsular (close to the nurse cell–parasite complex) and extra-capsular (where the parasite was not visible) areas. The increase in the number of nuclei in the muscle tissues of Trichinella-infected mice was considered an inflammation marker, since uninfected muscles show low nucleus density. In order to evaluate differences in the nitrosylation pattern between encapsulated (T. spiralis, T. britovi) and non-encapsulated (T. pseudospiralis, Trichinella papuae, Trichinella zimbabwensis) species, L1 larvae were tested by immunoblotting with an anti-nitrotyrosine polyclonal antibody. Inflammation induced by T. spiralis larvae in muscle tissues is statistically higher than that elicited by the other species, both in peri- and extra-capsular areas. Nitrosylation occurs at a higher level in encapsulated than in non-encapsulated species. The method developed in this work allows demonstration of differences in the host inflammatory response against encapsulated and non-encapsulated Trichinella species.
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.
M. Paradisi, M. Fernández, G. Del Vecchio, G. Lizzo, G. Marucci, M. Giulioni, E. Pozzati, T. Antonelli, G. Lanzoni, G. P. Bagnara, L. Giardino and L. Calzà (2010) Neuropathology and Applied ...Neurobiology36, 535–550 Ex vivo study of dentate gyrus neurogenesis in human pharmacoresistant temporal lobe epilepsy
Aims: Neurogenesis in adult humans occurs in at least two areas of the brain, the subventricular zone of the telencephalon and the subgranular layer of the dentate gyrus in the hippocampal formation. We studied dentate gyrus subgranular layer neurogenesis in patients subjected to tailored antero‐mesial temporal resection including amygdalohippocampectomy due to pharmacoresistant temporal lobe epilepsy (TLE) using the in vitro neurosphere assay. Methods: Sixteen patients were enrolled in the study; mesial temporal sclerosis (MTS) was present in eight patients. Neurogenesis was investigated by ex vivo neurosphere expansion in the presence of mitogens (epidermal growth factor + basic fibroblast growth factor) and spontaneous differentiation after mitogen withdrawal. Growth factor synthesis was investigated by qRT‐PCR in neurospheres. Results: We demonstrate that in vitro proliferation of cells derived from dentate gyrus of TLE patients is dependent on disease duration. Moreover, the presence of MTS impairs proliferation. As long as in vitro proliferation occurs, neurogenesis is maintained, and cells expressing a mature neurone phenotype (TuJ1, MAP2, GAD) are spontaneously formed after mitogen withdrawal. Finally, formed neurospheres express mRNAs encoding for growth (vascular endothelial growth factor) as well as neurotrophic factors (brain‐derived neurotrophic factor, ciliary neurotrophic factor, glial‐derived neurotrophic factor, nerve growth factor). Conclusion: We demonstrated that residual neurogenesis in the subgranular layer of the dentate gyrus in TLE is dependent on diseases duration and absent in MTS.
Molecular analyses such as polymerase chain reaction (PCR) and sequencing are very useful for taxon identification, especially when morphological characters useful for identifying taxa are lacking. ...However, the use of molecular tools can be the source of taxon misidentification if they are not correctly applied and the results are not critically evaluated and compared with the literature and GenBank data. We describe a case of misidentification of a taxon of the genus Trichinella due to sequencing mistakes, lack of reference material and selection of a single molecular marker. A Trichinella sp. isolate from an Iranian wild boar (Sus scrofa) was identified as belonging to the Nearctic species Trichinella murrelli, through the molecular analysis of the 5S rRNA intergenic spacer region. A successive molecular identification of the same isolate was performed by the International Trichinella Reference Centre in Rome, Italy, using the 5S rRNA intergenic spacer region, the LSU rDNA expansion segment five, and the internal transcribed spacers 1 and 2. According to these analyses, the Iranian isolate belonged to Trichinella britovi, a Palaearctic species already described in Iran.
Trichinella infections in horses continue to represent a health problem and, despite the rarity of infection, it is necessary to continue to control properly horse meat. In 2008, a 10-year-old horse ...imported from Poland to Italy for consumption found to have been positive at the digestion test. Both
Trichinella britovi and
Trichinella spiralis larvae in a proportion of 4:1 were detected in the horse muscles. This is the first report of a mixed
Trichinella species infection in a horse. The epidemiological investigation revealed that the infected horse originated from a small farm about 120
km from Warsaw and the horse owner had bought the horse at a horse market. The findings suggest that the horse was fed more than once with infected meat.
Thyrotropin-secreting adenomas (TSH-As) are rare and, according to the World Health Organization criteria (WHO 2004), a significant proportion of them present features of atypical adenomas at the ...time of diagnosis.
To determine the frequency of "atypical adenomas" and the significance of this definition as regards follow-up. To investigate their possible association with Hashimoto thyroiditis, leading to a delay in diagnosis.
Case notes for patients who underwent trans-sphenoidal surgery between 1992 and 2006 were retrieved. Follow-up ranged from 6 to 180 months.
Ten cases of TSH-As out of 908 pituitary adenomas were selected. Before surgery, eight patients had hyperthyroidism, one was euthyroid and another one showed hypothyroidism associated with Hashimoto thyroiditis. All cases were macroadenomas; six of them were invasive. Three cases met the criteria for classification as atypical. In none of the cases, including the three "atypical adenomas", were clinical or radiological signs of recurrence observed.
The three cases with features of atypical adenoma did not recur or metastasise, suggesting that, at least in the present series, a strict relationship between the morphological criteria for diagnosing atypical adenomas and biological behaviour may be sometimes lacking. Furthermore, the casual association of TSH-As with Hashimoto thyroiditis may led to an adjunctive delay in diagnosis, because of low thyroid hormone levels.
Glioblastoma (GBM) is the most frequent primary malignant brain tumour. Despite advances in treatment its prognosis remains poor. Histological features of GBM are well known. On the contrary ...histological description of recurrences is still not available. The aim of this study was to describe the morphological, immunohistochemical and molecular features of recurrent GBMs.
25 recurrent GBMs, diagnosed after 2005, were collected. All patients had undergone an adjuvant treatment regimen (temozolomide and/or radiotherapy). All cases were immunostained using anti-GFAP, Olig2 and Nogo-A antisera. MGMT and IDH1 status was reassessed. Features of the recurrences were compared with those of primary GBMs, time of recurrence and survival.
Recurrences were divided morphologically into three groups: 1) recurrences displaying the same features of primary GBM, were highly cellular, had the fastest progression and the worst prognosis; 2) recurrences changing dramatically morphological appearance, had a slightly longer survival, 3) poorly cellular recurrences, with sparse neoplastic cells intermingled with reactive and necrotic tissue, displayed the slowest progression and longer survival. MGMT and IDH1 status remained unchanged between primary tumours and recurrences.
GBM histological subtypes display different reactions to adjuvant treatments, offering a possible role in predicting different recurrence and survival time.
The red fox (
Vulpes vulpes) is considered one of the main reservoir of
Trichinella spp. in Europe. As limited information on
Trichinella infection in wildlife of Hungary is available, 2116 red ...foxes, representing more than 3% of the estimated fox population of the country, were screened to detect
Trichinella larvae by a digestion method.
Trichinella larvae from the 35 positive foxes were identified by a multiplex PCR as
Trichinella britovi (30 isolates, 85.7%),
Trichinella spiralis (4 isolates, 11.4%), and
Trichinella pseudospiralis (1 isolate, 2.9%). The true mean intensity of
T. britovi, T. spiralis and
T. pseudospiralis larvae in lower forelimb muscles was 23.6, 3.5 and 13.5
larvae/g, respectively.
T. spiralis was detected only in the southern and eastern regions. The non-encapsulated
T. pseudospiralis was recorded for the first time in Hungary. Although the overall true prevalence of
Trichinella infection in foxes was only 1.8% (95% confidence interval, CI
=
1.5–2.1%), the spatial analysis reveals different risk regions. In the north-eastern counties bordering Slovakia and Ukraine (21% of the Hungarian territory), the true prevalence of
Trichinella infection is significantly higher than that observed in other regions (6.0%, CI
=
4.8–7.1%). In the southern counties bordering Croatia, Serbia and Romania (41% of the Hungarian territory), the true prevalence of
Trichinella infection is moderate (1.4%, CI
=
1.0–1.8%). In the north-western and central counties (38% of Hungarian territory), the prevalence of
Trichinella infection is significantly lower (0.2%, CI
=
0.1–0.4%) than that of the other regions. Based on the statistical analysis and the evaluation of epidemiological data, none of the counties can be considered free of
Trichinella infection. In the past decade,
Trichinella infection has been detected only in few backyard pigs, and only few wild boar-related autochthonous infections in humans were described. Nevertheless, these results highlight the need of the maintenance of a strict monitoring and control programmes on
Trichinella infection in farmed and hunted animals of Hungary.
