First molecular identification of the zoonotic parasite Anisakis pegreffii (Nematoda: Anisakidae) in a paraffin-embedded granuloma taken from a case of human intestinal anisakiasis in Italy

<p>Abstract</p> <p>Background</p> <p>Anisakiasis is an important fish-borne zoonosis provoked by larval stages of nematodes belonging to the genus <it>Anisakis</it>. The detection and identification of human infections is difficult. This is due to: a) the low specificity of the clinical features and symptomatology related to human infections; b) the paucity of diagnostic features of larvae found in granulomatous lesions characteristic of "invasive anisakiasis"; and c) the lack morphological characters diagnostic at the specific level when larvae of <it>Anisakis </it>are detected. Thus, molecular-based diagnostic approaches are warranted.</p> <p>Method</p> <p>We have developed a PCR method that amplifies the DNA of <it>Anisakis </it>spp. in fixed paraffin-embedded tissues. This method was applied to a granuloma removed from a human case of intestinal anisakiasis in Italy. Specific primers of the mtDNA <it>cox2 </it>gene were used and sequence analysis was performed according to the procedures already established for species of <it>Anisakis</it>.</p> <p>Results</p> <p>The sequence obtained (629 bp) was compared with those of the other species of <it>Anisakis </it>which have so far been genetically characterized and with sequences obtained from larval stages of <it>Anisakis </it>collected from the Mediterranean fish <it>Engraulis encrasicolus</it>. This enabled the genetic identification of the larva in the human tissue as <it>A. pegreffii</it>. This is the first instance of human intestinal anisakiasis diagnosed using PCR of DNA purified from a fixed eosinophilic granuloma embedded in paraffin.</p> <p>Conclusion</p> <p>The case of human anisakiasis presented reinforces the pathological significance of the species <it>A. pegreffii </it>to humans. The molecular/genetic methodological approach based on mtDNA <it>cox2 </it>sequence analysis, described here, can allow easy and rapid identification of <it>Anisakis </it>spp. in formalin-fixed and paraffin embedded tissues removed from cases of either gastric or intestinal human anisakiasis.</p

Topical rapamycin inhibits tuberous sclerosis tumor growth in a nude mouse model

<p>Abstract</p> <p>Background</p> <p>Skin manifestations of Tuberous Sclerosis Complex (TSC) cause significant morbidity. The molecular mechanism underlying TSC is understood and there is evidence that systemic treatment with rapamycin or other mTOR inhibitors may be a useful approach to targeted therapy for the kidney and brain manifestations. Here we investigate topical rapamycin in a mouse model for TSC-related tumors.</p> <p>Methods</p> <p>0.4% and 0.8% rapamycin ointments were applied to nude mice bearing subcutaneous, TSC-related tumors. Topical treatments were compared with injected rapamycin and topical vehicle. Rapamycin levels in blood and tumors were measured to assess systemic drug levels in all cohorts.</p> <p>Results</p> <p>Treatment with topical rapamycin improved survival and reduced tumor growth. Topical rapamycin treatment resulted in systemic drug levels within the known therapeutic range and was not as effective as injected rapamycin.</p> <p>Conclusion</p> <p>Topical rapamycin inhibits TSC-related tumor growth. These findings could lead to a novel treatment approach for facial angiofibromas and other TSC skin lesions.</p

Rapamycin Blocks Production of KSHV/HHV8: Insights into the Anti-Tumor Activity of an Immunosuppressant Drug

Infection with Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) often results in the development of fatal tumors in immunocompromised patients. Studies of renal transplant recipients show that use of the immunosuppressant drug rapamycin, an mTOR inhibitor, both prevents and can induce the regression of Kaposi's sarcoma (KS), an opportunistic tumor that arises within a subset of this infected population. In light of rapamycin's marked anti-KS activity, we tested whether the drug might directly inhibit the KSHV life cycle. We focused on the molecular switch that triggers this predominantly latent virus to enter the lytic (productive) replication phase, since earlier work links this transition to viral persistence and tumorigenesis.In latently infected human B cell lines, we found that rapamycin inhibited entry of the virus into the lytic replication cycle, marked by a loss of expression of the lytic switch protein, replication and transcription activator (RTA). To test for viral-specific effects of rapamycin, we focused our studies on a B cell line with resistance to rapamycin-mediated growth inhibition. Using this line, we found that the drug had minimal effect on cell cycle profiles, cellular proliferation, or the expression of other cellular or latent viral proteins, indicating that the RTA suppression was not a result of global cellular dysregulation. Finally, treatment with rapamycin blocked the production of progeny virions.These results indicate that mTOR plays a role in the regulation of RTA expression and, therefore, KSHV production, providing a potential molecular explanation for the marked clinical success of rapamycin in the treatment and prevention of post-transplant Kaposi's sarcoma. The striking inhibition of rapamycin on KSHV lytic replication, thus, helps explain the apparent paradox of an immunosuppressant drug suppressing the pathogenesis of an opportunistic viral infection

A lycopene and olives vegetation water compound improves lower urinary tract symptoms in men with histologically-proven benign prostatic hyperplasia and inflammation

Background and aims. There is evidence for the ability of antioxidants to counteract the effects of inflammation. We aimed to determine whether the administration of a lycopene/olives vegetation water compound might reduce prostatic inflammation and consequent lower urinary tract symptoms in patients with histologically proven prostatic inflammation. Methods. Over a month period, patients having undergone prostate biopsy and having been diagnosed with benign prostate were given lycopene/olives vegetarian water compound (Group A). Data were compared with those of a matched population of patients who did not receive such treatment (Group B). International prostate symptom score, peak flow rate and post-void residual were recorded before and at the end of treatment. Results. The 17 patients in group A and the 17 in group B, had similar age, PSA, prostate volume, peak flow rate and post-void residual, but patients in Group A had lower median international prostate symptoms score than those in group B (7 vs 12; p = 0.012). All patients in group A successfully completed treatment with no side effect. Group B experienced no difference in international prostate symptoms score, peak flow rate and post-void residual whereas group A experienced no difference in peak flow rate, a slight reduction in post-void residual and a decrease in international prostate symptoms score. Most important, reduction in international prostate symptoms score was significantly higher in group A than in group B (-2.0 vs 0, respectively; p = 0.0004). Conclusions. The lycopene/olives vegetation water compound seems to be effective in counteracting lower urinary tract symptoms due to prostatic inflammation

Waist-to-Height Ratio is the Best Anthropometric index in Association with Adverse Cardiorenal Outcomes in Type 2 Diabetes Mellitus Patients

Background/Aims: Visceral obesity is a potent risk factor for both chronic kidney disease (CKD) and myocardial infarction (MI) in type 2 diabetes mellitus patients (T2DM). Short stature is also associated with higher risk for either coronary or kidney diseases. Thus, the aim of our study was to investigate the association of the frequency of cardiorenal complications with waist-to-height index (W/Ht) in T2DM. Methods: This was a cross-sectional study where 958 T2DM patients were studied. Subjects with cardiorenal disease (CRD) were defined as those with both kidney dysfunction (KD) and MI. Results: We found a significant excess of MI in patients with KD as compared to those without KD (28 vs. 14%, p < 0.0001). Interestingly, among the commonly used indices of obesity, only W/Ht and BMI were significantly associated with CRD risk. Moreover, only the W/Ht index (but neither BMI nor WC) was significantly associated with the risks for every component of CRD. Lastly, in the multivariate logistic regression analysis, W/Ht proved superior to the other traditional factors associated with risk for CRD. Conclusions: Our study in a large cohort of subjects demonstrated that a higher W/Ht index is the best anthropometric measure associated with adverse CRD outcomes of T2DM patients