Search

The study of pathogenicity and virulence of fungal strains, in vivo in the preclinical phase, is carried out through the use of animal models belonging to various classes of mammals (rodents, leproids, etc.). Although animals are functionally more similar to humans, these studies have some limitations in terms of ethics (animal suffering), user-friendliness, cost-effectiveness, timing (physiological response time) and logistics (need for adequately equipped laboratories). A good in vivo model must possess some optimal characteristics to be used, such as rapid growth, small size and short life cycle. For this reason, insects, such as Galleria mellonella (Lepidoptera), Drosophila melanogaster (Diptera) and Bombyx mori (Lepidoptera), have been widely used as alternative non-mammalian models. Due to their simplicity of use and low cost, the larvae of G. mellonella represent an optimal model above all to evaluate the virulence of fungal pathogens and the use of antifungal treatments (either single or in combination with biologically active compounds). A further advantage is also represented by their simple neuronal system limiting the suffering of the animal itself, their ability to survive at near-body ambient temperatures as well as the expression of proteins able to recognise combined pathogens following the three R principles (replacement, refinement and reduction). This review aims to assess the validity as well as the advantages and disadvantages of replacing mammalian classes with G. mellonella as an in vivo study model for preclinical experimentation.

Emerging life-threatening multidrug-resistant (MDR) species such as the C. haemulonii species complex, Clavispora lusitaniae (sin. C. lusitaniae ), and other Candida species are considered as an increasing risk for human health in the near future. (1) Background: Many studies have emphasized that the increase in drug resistance can be associated with several virulence factors in Candida and its knowledge is also essential in developing new antifungal strategies. (2) Methods: Hydrophobicity, adherence, biofilm formation, lipase activity, resistance to osmotic stress, and virulence 'in vivo' on G. mellonella larvae were studied in isolates of C. haemulonii , C. albicans , and C. lusitaniae with low susceptibility and resistance to fluconazole and amphotericin B. (3) Results: Intra- and interspecies variability were observed. C. haemulonii showed high hydrophobicity and the ability to adhere to and form biofilm. C. lusitaniae was less hydrophobic, was biofilm-formation-strain-dependent, and did not show lipase activity. Larvae inoculated with C. albicans isolates displayed significantly higher mortality rates than those infected with C. haemulonii and C. lusitaniae . (4) Conclusions: The ability to adhere to and form biofilms associated with their hydrophobic capacity, to adapt to stress, and to infect within an in vivo model, observed in these non-wild-type Candida and Clavispora isolates, shows their marked virulence features. Since factors that define virulence are related to the development of the resistance of these fungi to the few antifungals available for clinical use, differences in the physiology of these cells must be considered to develop new antifungal therapies.

Recent work has been developed on two new classes of neutral porphyrazine complexes of formulas [(PdCl 2 ) 4 Py 8 PzM]· x H 2 O (Py 8 Pz = octakis(2-pyridyl)porphyrazinato anion; M = Mg II (H 2 O), Zn II , Pd II ) and [{Pd(CBT) 2 } 4 Py 8 PzM]· x H 2 O (M = Mg II (H 2 O), Zn II ; CBT = m -carborane-1-thiolate anion). Characterization of all the species has been conducted by IR and UV-visible spectral measurements in a systematic comparison with the corresponding already known mononuclear species [Py 8 PzM] (M = Mg II (H 2 O), Zn II ) and the mono-Pd II analogue isolated and presented here for the first time. Comparison includes also the two parent classes of pentanuclear tetrapyrazinoporphyrazines having the more extended π-electron delocalized macrocyclic core Py 8 TPyzPz. The reported new classes of pentanuclear complexes behave as active photosensitizers in photodynamic therapy (PDT), and due to the high boron content of the CBT derivatives, perspectives for them are open of application in the field of bimodal PDT/BNCT (boron neutron capture therapy) anticancer treatments.

The new synthesized Pd II complex cis -[(bipy)Pd(CBT) 2 ] (bipy = 2,2'-bipyridyl; CBT = m -carborane-1-thiolate anion), which is a potential BNCT (boron neutron capture therapy) agent and of structure elucidated by single-crystal X-ray work, has been studied by infrared (IR) and ultraviolet-visible light (UV-vis) spectra and its properties compared with those of the previously reported and also the structurally characterized analogue trans -[(py) 2 Pd(CBT) 2 ]. This trans species, prepared via a direct method, was previously isolated from a pyridine solution, consequent to the occurring releasing of the external Pd(CBT) 2 moieties of the porphyrazine macrocycle [{Pd(CBT) 2 } 4 LZn]· x H 2 O (L = tetrakis-2,3-[5,6-di(2-pyridyl)pyrazino]porphyrazinato anion), which is an active photosensitizer in photodynamic therapy (PDT) and a potential bimodal PDT/BNCT agent. The UV-vis spectral behavior of both cis and trans species in CHCl 3 solution and in the gas phase has been examined in detail by density functional theory (DFT) and time-dependent density functional theory (TDDFT) studies devoted to explain their distinct behavior observed in the region of 400-500 nm, as determined by the presence in the cis structure of a vicinal arrangement of the two CBT groups, an ensemble of results closely similar to those observed for the macrocycles [{Pd(CBT) 2 } 4 LM]· x H 2 O (M = Mg II (H 2 O), Zn II , Pd II ). It has also been experimentally proved the tendency of the cis isomer in CHCl 3 /pyridine solution to be changed to the respective trans analogue, with conversion occurring in two steps, as interpreted by detailed DFT studies.

The already known di(2-pyridyl)dihydropyrazine (dhdpp) was prepared and isolated also in the form of a bis-hydrated species, i.e., dhdpp·2H 2 O. As established by X-ray work, a small amount of single crystals of di(2-pyridyl)-pyrazine (dpp) was also obtained from the mother liquors, this testifying the possibility of a dehydrogenation process dhdpp → dpp in the absence of a catalyst. Using dhdpp as a ligand, mononuclear metal derivatives of formula [(dhdpp)MCl 2 ]· x H 2 O (M = Pd II , Pt II ) were obtained as stable-to-air solids, studied by X-ray powder, IR, UV-visible, and 1 H NMR spectra, and proved to exhibit a N 2 MCl 2 coordination site involving one pyridine and one pyrazine N atom ("py-pyz" coordination). An interesting relationship has been established in terms of the observed types of coordination with the analogs of di(2-pyridyl)-pyrazine (dpp) formulated as [(dpp)MCl 2 ]·3H 2 O, proved also by 1 H NMR spectra to exhibit the "py-pyz" mode of coordination. Attempts to isolate from the reaction of dhdpp with Pd(OAc) 2 the corresponding mononuclear derivatives were shown to lead, as definitely supported by 1 H NMR spectral data and crystallographic work, to the exclusive formation of the corresponding dpp complex [(dpp)Pd(OAc) 2 ]·5H 2 O ("py-pyz" coordination site), this proving the tendency of dhdpp to generate dpp under different reaction conditions. The promoted conversion of dhdpp into dpp in the complex was examined by sequential NMR analysis and established to be determined by Pd(OAc) 2 which plays the role of catalyst. The new salt-like species [(CH 3 )(dhdpp)PdI 2 ](I)·7H 2 O, prepared starting from [(dhdpp)PdCl 2 ] in its reaction with CH 3 I, allowed the separation from the mother liquors of small brown crystals identified on the basis of X-ray analysis as the already known complex of formula [(dpp)PdI 2 ] ("py-py" coordination), this result once again outlining the tendency of dhdpp to be dehydrogenated to dpp.

Background: Acute biliary pancreatitis (ABP) still retains high morbidity (15-50%) and mortality (20-35%). Therefore it appears to be crucial to clearly assess the aetiological factors (50% of idiopathic are in fact biliary pancreatitis) and to establish their severity in order to plan the appropriate treatment., Methods: 58 ABP patients were diagnosed by ultrasound (77.5%) or by laboratory findings (22.4%). Following Ranson and APACHE II scoring 17 cases (29.3%) were classified as severe, 41 (70.6%) as mild. All patients with severe ABP, had emergency ERCP + ES (within 24-48 hrs) followed by LC (< or = 10 days). Patients with mild ABP had LC within 10 days; in these cases IOC was always done., Results: In severe cases operative endoscopy cured pancreatic inflammation in 12 cases. Subsequent LC never showed serious morbidity, apart from subcutaneous emphysema in one case. In 5 cases laparotomy was required since pancreatic necrosis was present, with 60% mortality. In patients with mild pancreatitis LC was successfully performed in all cases, with 7.3% morbidity. IOC showed choledochal stones in 31.7% of cases, while in severe cases stones in the biliary tree were shown in 88.2% of cases., Conclusions: In conclusion ABP treatment is always surgical, and almost always with minimally-invasive procedures in severe cases (ERCP + ES with LC < or = 10 days) if surgery is performed within 24-48 hrs as well as in mild cases (LC + IOC) when surgery is done within 10 days.

Background: Acute biliary pancreatitis (ABP) still retains high morbidity (15-50%) and mortality (20-35%). Therefore it appears to be crucial to clearly assess the aetiological factors (50% of idiopathic are in fact biliary pancreatitis) and to establish the severity in order to plan the appropriate treatment., Methods: In this study we have considered 61 patients divided into 2 groups. Group 1 had 29 ABP patients aging less than 65 years, group 232 patients aging more than 65 years; the diagnosis was made by ultrasound and serological values in 78.5% of cases, while in the remaining 21.5% was only serological. Following Ranson and APACHE II scoring 18 cases (29.5%) were classified as severe [6 (20.6%) in group 1; 12 (37.5%) in group 2: p < 0.01], 43 (70.4%) as mild. All patients with severe ABP had emergency ERCP + ES (within 24-48 hrs) followed by LC (< or = 10 days). Patients with mild ABP had LC within 10 days; in these cases IOC was always done., Results: In severe cases operative endoscopy cured pancreatic inflammation in 13 cases. Subsequent LC never showed serious morbidity, apart subcutaneous emphysema in one case. In 5 cases laparotomy was required since pancreatic necrosis was present, with 60% mortality. In patients with mild pancreatitis LC was successfully performed in all cases, with 6.9% morbidity. IOC showed choledochal stones in 32.5% of cases, while in severe cases stones in the biliary tree were showed in 88.8% of cases. No significant differences were detected between group 1 and 2., Conclusions: In conclusion ABP treatment is always surgical, and almost always with minimally-invasive procedures in severe cases (ERCP + ES with LC < or = 10 days) if surgery is performed within 24-48 hrs as well as in mild cases (LC + IOC) when surgery is done within 10 days, independently from the age of the patients.

The "Sump Syndrome" represents a known late complication not easily recognizable within the interventions of CDS and L-L CDS. Its incidence ranges from 0% to 9.6% according to the literature. Up to ten years ago the "Sump Syndrome" treatment was mostly surgical. Currently endoscopic treatment reduces considerably the operative risk and the number, frequency and severity of complications. The technique consists of an endoscopic papillosphincterotomy with removal of calculus, gall mud, alimentary fragments and restoration of a satisfactory flow towards the duodenum. From January 1985 to October 1993, 492 ERCP were performed in Popoli's Hospital Digestive Department with an overall success rate of 92% and a selective incannulation success rate of 87%. Endoscopic treatment was used in 56% of the cases (319 patients) with 90% of success; 271 patients (35%) with lithiasic pathology were examined and 35 (12.9%) of them presented the "Sump Syndrome". Six patients underwent operation, 2 had no treatment and 27 underwent endoscopic treatment. In 21 cases an endoscopic papillotomy was performed and in 6 cases a bile-duct washing or calculi fragmentation was assured; 21 patients recovered completely while 6 patients still refer a painful-dyspeptic symptomatology with occasional colics which could be related to phenomena of chronic pancreatitis. The clinical experience allowed us to positively evaluate the endoscopic treatment of the "Sump Syndrome" since it carries a low mortality and morbidity rate and, furthermore, it is easily repeatable.

Acute biliary pancreatitis (ABP) still retains high morbidity (15-50%) and mortality (20-35%). Therefore it appears to be crucial clearly assessing the aetiological factors (50% of idiopathic are in fact biliary pancreatitis) and establishing the severity in order to plan the appropriate treatment. Forty-nine ABP patients were diagnosed by ultrasound (75.5%) or by laboratory findings (22.5%). Following Ranson and APACHE II scoring, 15 cases (30.6%) were classified as severe, 34 (69.3%) as mild. All patients with severe ABP had emergency ERCP + ES (within 24-48 hours) followed by LC (< or = 10 days). Patients with mild ABP had LC within 10 days; in these cases IOC was always done. In severe cases operative endoscopy cured pancreatic inflammation in 11 cases. Subsequent LC never showed serious morbidity, but subcutaneous emphysema in one case. In 4 cases laparotomy was required since pancreatic necrosis was present, with 75% mortality. In patients with mild pancreatitis LC was successfully performed in all cases, with 8.8% morbidity. IOC showed choledochal stones in 32.5% of cases, while in severe cases stones in the biliary tree were showed in 80% of cases. In conclusion ABP treatment is always surgical, and almost always with minimally-invasive procedures in severe cases (ERCP + ES with LC < or = 10 days) if surgery is performed within 24-48 hours as well as in mild cases (LC + IOC) when surgery is done within 10 days.

The diagnosis of bleeding of gastrointestinal low tract is still a very controversial subject. At the Service of Digestive Endoscopy of Popoli (PE) Hospital, in a period of 4 years, 2074 colonoscopies have been effected. In 640 cases, that is 30.8%, the indication for the exam was suggested by rectal bleeding. In the 566 patients examined for minor rectal bleeding, the most frequent lesions were: haemorrhoids (35.3%), polyps (15.2%), malignant neoplastic disease (9.3%). In all active rectal haemorrhages (14 massive, 41 medium) an urgent colonoscopy has been carried out with a percentage of success of 90%; in the 20 cases of unexplained melena, colonoscopy has not led to a diagnosis; in the 14 patients with unexplained anemia, colonoscopy has shown 2 carcinomas, whereas in the 5 cases with occult blood in stools it has been diagnostic in the percentage of 60%. We have ascertained that, when barium enema was effected before colonoscopy, the diagnostic agreement between the two examinations was only of 21.4 (9/42); on the contrary there was an agreement of 95% when colonoscopy was effected before barium enema. In accordance with Siewert and Blum (25), Ottenjann (24) and Farrands (42), we believe that colonoscopy should be considered the main examination after either major or minor rectal bleeding, because it is a quick and safe investigation with high diagnostic specificity and sensitivity. We refuse William's position (41), because, even in presence of haemorrhoids or anal fissures, the colon must be studied as a whole, especially in a period when neoplastic disease of this tract of intestine is considerably increasing.(ABSTRACT TRUNCATED AT 250 WORDS)