Antileishmanial activity of natural diterpenes from Cistus sp. and semisynthetic derivatives thereof

Eleven cis-clerodane diterpenes, seven labdane type diterpenes and one triterpene isolated from Cistus monspeliensis and the resin "Ladano" of Cistus creticus subsp. creticus were evaluated against Leishmania donovani promastigotes, the causative agent for visceral leishmaniasis. In addition, eleven semisynthetic manoyl oxide, seventeen labdane type derivatives and a triterpene were also evaluated for their antileishmanial activity. 18-Acetoxy-cis-clerod-3-en-15-ol, 15,18-diacetoxy-cis-clerod-3-ene and 13-(E)-8a-hydroxylabd-13-en-15-ol 2-chloroethylcarbamate exhibited the most potent and selective leishmanicidal activity with IC50 values of 3.3 microg/ml, 3.4 microg/ml and 3.5 microg/ml, respectively.     

Risk factors for Age-related Macular Degeneration in a Greek population: The Thessaloniki Eye Study

Purpose: To assess the association of potential risk factors with early and late age-related macular degeneration (AMD) in the Thessaloniki Eye Study (TES) population

Design: Population-based, cross-sectional study of subjects over age of 60 living in Thessaloniki, Greece

Methods: Subjects without any AMD features and subjects with early and late AMD (neovascular AMD or geographic atrophy) were identified in the TES cohort using standardized procedures and masked grading of stereo color fundus photos. Demographic, lifestyle, systemic and other ophthalmic covariates were also collected during a detailed examination process. Their association with AMD was investigated using univariate and multivariate adjusted logistic regression models.

Results: Among the 2108 participants with gradable photos, the grading process identified 1204 subjects with no AMD, 848 subjects with early AMD, and 56 subjects with late AMD (24 with geographic atrophy and 32 with neovascular AMD). In multivariate analysis, compared to no AMD, late AMD was positively associated with older age (OR:1.16; 95%CI:1.10–1.22 per year of age), current smoking (smoking vs. never smoking, OR:2.34; 95%CI:1.12–4.90), prior cataract surgery (cataract surgery vs. no cataract surgery OR:2.06; 95%CI:0.96–4.40), marital status (divorced/separated vs. married, OR:3.10; 95%CI:1.08–8.93) and with 60% lower odds when sleeping in the afternoon (yes vs. no, OR:0.40; 95%CI:0.22–0.72). Early AMD was positively associated with older age (OR: 1.03; 95%CI:1.01–1.05 per year of age) and negatively with higher pulse pressure (OR:0.99; 95%CI:0.98–0.99 per mmHg).

Conclusions: In TES, apart for well-known risk factors for AMD like age, smoking, and cataract surgery, two novel behavioral risk factors for prevalent late AMD were suggested. Sleeping in the afternoon was associated with 60% decreased odds for late AMD and 67% decreased odds for neovascular AMD. Being divorced/separated compared to married was associated with 3-fold higher odds for late AMD. Large longitudinal population-based studies will be necessary to further establish the potential late AMD risk effects of these two novel factors, to demonstrate potential implications of underlying pathogenetic mechanisms, and to explore preventive measures and therapeutic targets.     

HPV detection rate in saliva may depend on the immune system efficiency

BACKGROUND: Human papilloma virus (HPV) has been established as a major etiological factor of anogenital cancer. In addition, HPV has also been implicated in oral carcinogenesis but its detection rates appear to be highly variable, depending on the patient population tested, the molecular methodology used, as well as the type of oral specimen investigated. For example, saliva is an oral fluid that may play a role in HPV transmission, although the detection rates of the virus are lower than tissue. Recent evidence has indicated that HPV-related pathology is increased in the oral cavity of human immunodeficiency virus (HIV)-positive individuals. In order to investigate whether the presence of different HPV types in saliva depends on immune system efficiency, oral fluid samples of patients with oral cancer and without any known immune deficiency were compared with those of HIV-positive individuals. PATIENTS AND METHODS: Saliva samples were collected from 68 patients with oral squamous cell carcinoma and 34 HIV seropositive individuals. HPV DNA sequences were detected by L1 concensus polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP) analysis and DNA sequencing for HPV typing. RESULTS: HPV DNA was detected in 7/68 (10.3%) of the oral cancer patients and in 12/34 (35.3%) of the HIV-positive individuals, a highly significant difference (p = 0.006; odds ratio 4.753; 95% confidence interval 1.698-13.271). Among HPV-positive samples, the prevalence of HPV types associated with high oncogenic risk was similar in oral cancer and HIV-positive cases (71.4% and 66.7%, respectively). In both groups, the most common HPV type was high-risk 16 (50% and 42.8%, respectively). CONCLUSION: Although a similar pattern of HPV high-risk types was detected in oral cancer and HIV-positive cases, the quantitative detection of HPV in saliva significantly depended on immune system efficiency. Furthermore, the significantly increased detection rates of HPV in saliva of HIV-positive individuals may be associated with high risk for development of HPV-related oral lesions, including malignancy.     

Epidemiology and management of cryptococcal meningitis: developments and challenges

The significance of cryptococcal infection as a cause of human disease has dramatically evolved in recent years. The objective of this study was to outline the worldwide significance of cryptococcosis and review developments in the management of cryptococcal meningitis. Cryptococcus neoformans var. grubii remains an important cause of disease, particularly in hosts with acquired immunosuppression. Cryptococcus gattii, on the other hand, infects hosts with seemingly normal immune systems and a recent dramatic outbreak in a new ecologic environment highlights the emerging clinical significance of this fungal pathogen. The introduction of new antifungal agents and the adoption of strategies for controlling elevated intracranial pressure in cryptococcal meningitis have added to our therapeutic options. However, the mortality from this infection remains unacceptably high and we are faced with the specific challenges in the management of this disease.     

Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma.

PURPOSE: The discovery of new ovarian cancer biomarkers that are suitable for early disease diagnosis and prognosis may ultimately lead to improved patient management and outcomes. PATIENTS AND METHODS: We measured, by immunoassay, human kallikrein 6 (hK6) concentration in serum of 97 apparently healthy women, 141 women with benign abdominal diseases, and 146 women with histologically proven primary ovarian carcinoma. We then calculated the diagnostic sensitivity and specificity of this test and examined the association of serum hK6 concentration with various clinicopathologic variables and patient survival. RESULTS: Serum hK6 concentration between normal and benign disease patients was not different (mean, 2.9 and 3.1 micro g/L, respectively). However, hK6 in presurgical serum of ovarian cancer patients was highly elevated (mean, 6.8 micro g/L; P <.001). Serum hK6 decreased after surgery (to a mean of 3.9 micro g/L) in 68% of patients. The diagnostic sensitivity of serum hK6 at 90% and 95% specificity is 52% and 47%, respectively, in the whole patient population. For early stage disease (stage I or II), sensitivity is approximately 21% to 26%. When combined with CA-125, at 90% specificity, sensitivity increases to 72% (for all patients) and to 42% in stage I or II disease. Serum hK6 concentration correlates moderately with CA-125 and is higher in patients with late-stage, higher-grade disease and in patients with serous histotype. Preoperative serum hK6 concentration is a powerful predictor of disease-free and overall survival in both univariate and multivariate analyses. CONCLUSIONS: Serum hK6 concentration seems to be a new biomarker for ovarian carcinoma and may have value for disease diagnosis and prognosis.     

Clinical significance and prognostic relevance of KRAS,BRAF, PI3K and TP53 genetic mutation analysis for resectable and unresectable colorectal liver metastases: A systematic review of the current evidence

Background

Hepatic resection is considered the optimal potentially curative treatment for colorectal liver metastases (CRLM). Following resection, up to two-thirds of patients will develop recurrence within 5-years. Genetic mutation analysis of CRLM, especially KRAS status, has been proposed as a means to guide treatment, as well as identifying patients who can derive the most survival benefit from hepatic resection.

Benign neurogenic tumors of the oral cavity

Neurogenic tumors are rare in the oral cavity, particularly so when malignant. Traumatic neuroma, although usually included with neurogenic tumors, is a reactive process rather than a true neoplasm. Neurofibroma and schwannoma derive from nerve fibers, the perineurium, the endoneurium and the neurolemmomal cells. They present histological differences. The neurofibroma may present in solitary and generalized types; the latter also known as neurofibromatosis or von Recklinghausen's disease of the skin. We here report typical cases of benign neurogenic tumors of the oral cavity.     

Characterization of “γ-Eye”: a Low-Cost Benchtop Mouse-Sized Gamma Camera for Dynamic and Static Imaging Studies

Purpose

Several preclinical imaging systems are commercially available, but their purchase and maintenance costs make them unaffordable for the majority of small- and medium-sized groups. Taking into account the needs of average users, we developed “γ-eye”, a mouse-sized, benchtop γ-camera suitable for in vivo scintigraphic imaging.

Procedures

The γ-eye is based on two position-sensitive photomultiplier tubes, coupled to a CsI(Na) pixelated scintillator and a low-energy lead collimator with parallel hexagonal holes.

Results

The spatial resolution of the system is 2 mm at 0 mm. The energy resolution is 26 % at 140 keV and the maximum recorded sensitivity 210 cps/MBq. The system was evaluated in a proof-of-concept animal study, using three different clinical Tc-99m-labeled radiopharmaceuticals. Phantom and animal studies demonstrate its ability to provide semiquantitative results even for short scans.

Conclusions

Systems’ performance, dimensions, and cost make γ-eye a unique solution for efficient whole-body mouse nuclear imaging.