Michela Pugliese

Hypericum perforatum: Pharmacokinetic, Mechanism of Action, Tolerability, and Clinical Drug-Drug Interactions

Hypericum perforatum (HP) belongs to the Hypericaceae family and is one of the oldest used and most extensively investigated medicinal herbs. The medicinal form comprises the leaves and flowering tops of which the primary ingredients of interest are naphthodianthrones, xanthones, flavonoids, phloroglucinols (e.g. hyperforin), and hypericin. Although several constituents elicit pharmacological effects that are consistent with HPs antidepressant activity, no single mechanism of action underlying these effects has thus far been found. Various clinical trials have shown that HP has a comparable antidepressant efficacy as some currently used antidepressant drugs in the treatment of mild/moderate depression. Interestingly, low‐hyperforin‐content preparations are effective in the treatment of depression. Moreover, HP is also used to treat certain forms of anxiety. However, HP can induce various cytochrome P450s isozymes and/or P‐glycoprotein, of which many drugs are substrates and which are the main origin of HP–drug interactions. Here, we analyse the existing evidence describing the clinical consequence of HP–drug interactions. Although some of the reported interactions are based on findings from in vitro studies, the clinical importance of which remain to be demonstrated, others are based on case reports where causality can, in some cases, be determined to reveal clinically significant interactions that suggest caution, consideration, and disclosure of potential interactions prior to informed use of HP. Copyright

Recognition of fungal RNA by TLR7 has a nonredundant role in host defense against experimental candidiasis

Despite convincing evidence for involvement of members of the Toll‐like receptor (TLR) family in fungal recognition, little is known of the functional role of individual TLRs in antifungal defenses. We found here that TLR7 was partially required for the induction of IL‐12 (IL‐12p70) by Candida albicans or Saccharomyces cerevisiae. Moreover, the IL‐12p70 response was completely abrogated in cells from 3d mice, which are unable to mob‐ilize TLRs to endosomal compartments, as well as in cells from mice lacking either the TLR adaptor MyD88 or the IRF1 transcription factor. Notably, purified fungal RNA recapitulated IL‐12p70 induction by whole yeast. Although RNA could also induce moderate TLR7‐dependent IL‐23 and tumor necrosis factor‐alpha (TNF‐α) secretion, TLR7 and other endosomal TLRs were redundant for IL‐23 or TNF‐α induction by whole fungi. Importantly, mice lacking TLR7 or IRF1 were hypersusceptible to systemic C. albicans infection. Our data suggest that IRF1 is downstream of a novel, nonredundant fungal recognition pathway that has RNA as a major target and requires phagosomal recruitment of intracellular TLRs. This pathway differs from those involved in IL‐23 or TNF‐α responses, which we show here to be independent from translocation of intracellular TLRs, phagocytosis, or phagosomal acidification.

Antibacterial, antioxidant and hypoglycaemic effects of Thymus capitatus (L.) Hoffmanns. et Link leaves' fractions

Abstract The aim of this study was to examine the bioactivity of the methanol fraction (MF) and n-hexane fraction (HF) of Thymus capitatus leaves in relation to their constituents analysed by gas chromatography and gas chromatography-mass spectrometry. The effects of T. capitatus on the growth of pathogenic bacteria associated with respiratory diseases (13 gram-positive and 4 gram-negative) were determined using a microdilution method. The MF was particularly effective on Streptococcus pneumoniae and Moraxella catarrhalis. The antioxidant activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), ferric-reducing antioxidant power and β-carotene bleaching assays. A strong activity using β-carotene bleaching test was observed with the MF (IC50 of 0.7 μg/mL after 30 min of incubation). In the hypoglycaemic test, a selective α-amylase inhibitory activity was detected with the HF begging the most active (IC50 of 422.5 μg/mL). T. capitatus may represent a source of natural bioactive compounds.

Cytokine mRNA quantification in gastro-intestinal biopsies of dogs with idiopathic chronic enteropathies by Real Time RT-PCR: preliminary results.

Cytokine mRNA quantification in gastro-intestinal biopsies of dogs with idiopathic chronic enteropathies by Real Time RT-PCR: preliminary results M. De Majo & M. Pugliese & S. Galia & G. Mazzullo & E. La Camera & M. T. Fera # Springer Science + Business Media B.V. 2008

Effects of size and location of regions of interest examined by use of contrast-enhanced ultrasonography on renal perfusion variables of dogs

OBJECTIVE To determine effects of the size and location of regions of interest (ROIs) in the renal cortex of unsedated dogs on renal perfusion variables determined by use of contrast-enhanced ultrasonography (CEUS). ANIMALS 12 client-owned adult (1.5 to 2 years old) Labrador Retrievers (8 males and 4 females; mean ± SD body weight, 27 ± 1.6 kg). PROCEDURES Each dog received 2 bolus injections of sulfur hexafluoride during CEUS. Three small oval ROIs (area of each ROI, 0.11 cm(2)) located in a row with a distance of 1 mm between adjacent ROIs and 1 large oval ROI (area, 1 cm(2)) that encompassed the 3 smaller ROIs were manually drawn in the renal cortex. The ROIs were located at a depth of 1.5 to 2.0 cm in the near field of the renal cortex. Software analysis of time-intensity curves within each ROI was used to identify peak enhancement, time to peak enhancement, regional blood flow, and mean transit time. RESULTS The location and size of the ROIs of unsedated dogs did not cause significant differences in the mean values of the renal perfusion variables. CONCLUSIONS AND CLINICAL RELEVANCE The development of CEUS has provided a unique means for visually examining and quantifying tissue perfusion. Results of this study indicated that it was possible to use small or large ROIs during renal CEUS to evaluate renal perfusion in dogs.

Comparison of effects of topical levobunolol to a combination of timolol-dorzolamide on intraocular pressure and pulse rate of healthy dogs.

Comparison of effects of topical levobunolol to a combination of timolol-dorzolamide on intraocular pressure and pulse rate of healthy dogs M. Pugliese & A. Scardillo & P. P. Niutta & A. Pugliese Published online: 22 July 2009 # Springer Science + Business Media B.V. 2009

Daily rhythm of some haematological parameters in Holstein bovine maintained under natural conditions in southern hemisfere

Abstract The aim of this study was to evaluate the daily rhythms of haematological responses in bovines under different environmental conditions and to investigate the differences between bulls and cows. Twelve Holstein bovines were divided into two groups according to their gender: Group A (6 cows, 2 years, 500 ± 25 kg), and Group B (6 bulls, 2 years, 520 ± 25 kg). Environmental temperature and relative humidity were recorded and the temperature humidity index (THI) was calculated. Blood samples were collected every 3 h over 24 h period, every three months (winter, spring, summer, autumn) and analysed for haematological parameters. A significant effect of season (p < 0.01) and of gender (p < 0.05) on all studied parameters, and a circadian rhythm of RBC, Hb and Hct in all periods were found. These results may enhance the knowledge of haematological changes in cattles under natural environmental conditions, and their adaptation to the temporisations imposed by the environment.

The effects of timolol maleate gel formulation 0.1% on intraocular pressure and pulse rate in dogs

the objectives of new topical formulations for the treatment of glaucoma are to reduce the intraocular pressure (IOP) and minimize the occurrence of side effects. the aim of this study was to determine the effects of topical application of timolol maleate gel formulation 0.1% applied once daily, on the intraocular pressure and pulse rate (Pr) in ten healthy dogs. a clinical blinded trial was performed over two different periods; each period was divided into a pretreatment phase (D0) and four days of treatment (D1-4), with a wash out period of 10 days. treatments consisted of administration of one drop of timolol 0.1% gel formulation once a day and artificial tears. The IOP and PR values were recorded in all animals five times daily (7:00 AM, 10:00 AM, 1:00 PM, 5:00 PM, and 9:00 PM). Adverse events (conjunctival hyperemia, discomfort, breathing, and allergic reaction) were documented. Compared with the placebo treatment, the topical treatment with timolol gel formulation resulted in a significant decrease in IOP and PR. Already 24 hours after administration, TMG induced a significant reduction in IOP. In the group treated with TMG the mean decrease in IOP was 3.4 mm hg (P<0.01), the mean decrease in Pr was 10.8 (P<0.01). topical administration of timolol maleate gel 0.1% formula was effective in lowering IOP in healthy dogs. the gel formulation improves bioavailability, but it seems there was no reduction in adverse cardiopulmonary effects.

Quantitative evaluation of canine urinary bladder transitional cell carcinoma using contrast-enhanced ultrasonography

BackgroundIn veterinary medicine, contrast-enhanced ultrasonography allowed the accurate quantification of liver, splenic and kidney vascularization in healthy dogs and the differentiation between malignant and benign hepatic, renal, and splenic nodules in dogs and cats based on perfusion patterns. The utility of contrast-enhanced ultrasonography in other applications is still under study.The aim of this study was to develop diagnostic criteria by contrast-enhanced ultrasonography in 8 client-owned adult dogs affected by urinary bladder transitional cell carcinoma with definitive diagnosis made by cytopathologic evaluation after suction biopsy. The contrast enhancement pattern and the quantification of blood flow parameters of this tumor were reported.ResultsExaminations with B-mode, Doppler ultrasonography and contrast-enhanced ultrasonography were performed in all not sedated dogs. Assessments of bladder masses and bladder wall infiltration were performed. Each dog received 2 bolus injections of sulfur hexafluoride during the contrast-enhanced ultrasonography. Quantitative analysis of the contrast-enhanced ultrasonography images were performed. For each dog, one region of interest was manually drawn around the entire tumor. Software analysis of contrast-enhanced time-intensity curves was used to identify peak enhancement, time to peak enhancement, regional blood volume, regional blood flow, and mean transit time.Contrast-enhanced ultrasonography showed an avid enhancement of the tumour tissue, with a heterogeneous or homogeneous pattern. The exam also showed the loss of planes between the lesion and the muscular layer. The presence of vascularized tissue through the bladder wall confirms the infiltrative feature of the tumour. Post-processing quantitative analysis showed a time-intensity curve with a rapid wash-in, a low level of signal intensity and a slow wash-out.ConclusionsContrast-enhanced ultrasonography provided useful clinical information and defined a vascular enhancement patterns and calculated parameters associated with TCC. It may be a useful, noninvasive and reproducible tool for detecting these tumors in dogs.

Medico-legal aspects of congenital heart diseases in buying and selling of pets

Aim: The veterinarian should be able to assess congenital and inherited malformations such as heart defects because they may be object of legal disputes. In this study, the authors report some cases of congenital heart defects in pets (dogs and cats) to clarify whether or not they may be considered a redhibitory defect. Materials and Methods: A total of 28 medical records of pets referred with suspected congenital heart disease were examined. All patients aged between 3 and 24 months underwent clinical examination, chest X-ray examination, electrocardiogram, and echocardiography and angiocardiography when necessary. Results: Congenital heart diseases or associated cardiac malformations were confirmed. Considering the above congenital diseases as redhibitory defect and the rights of the owners from a strictly legal viewpoint, 9 owners demanded an estimatory action and 11 a redhibitory action; 1 owner decided to demand the reimbursement of veterinary expenses because the animal died; 7 owners took no legal action but requested surgical intervention. Conclusions: Until more appropriate and detailed legislation on the buying and selling of pet animals is put in place; the authors propose to include in the contract a temporal extension of the guarantee relating to congenital heart disease, which can often become evident later.