Serum hyaluronate as a non-invasive marker of hepatic fibrosis and inflammation in HBeAg-negative chronic hepatitis B

Background  

HBV infection is a serious global heath problem. It is crucial to monitor this disease more closely with a non-invasive marker in clinical trials. We aimed to evaluate the predictive value of serum hyaluronate for the presence of extensive liver fibrosis and inflammation.     

Multiple interaction sites of galnon trigger its biological effects

Galnon was first reported as a low molecular weight non-peptide agonist at galanin receptors [Saar et al. (2002) Proc. Natl. Acad. Sci. USA 99, 7136-7141]. Following its systemic administration, this synthetic ligand affected a range of important physiological processes including appetite, seizures and pain. Physiological activity of galnon could not be explained solely by the activation of the three known galanin receptors, GalR1, GalR2 and GalR3. Consequently, it was possible that galnon generates its manifold effects by interacting with other signaling pathway components, in addition to via GalR1-3. In this report, we establish that galnon: (i) can penetrate across the plasma membrane of cells, (ii) can activate intracellular G-proteins directly independent of receptor activation thereby triggering downstream signaling, (iii) demonstrates selectivity for different G-proteins, and (iiii) is a ligand to other G-protein coupled receptors (GPCRs) in addition to via GalR1-3. We conclude that galnon has multiple sites of interaction within the GPCR signaling cascade which mediate its physiological effects.     

Evaluation of the gastric antiulcerogenic effects of Portulaca oleracea L. extracts in mice

Portulaca oleracea is commonly used in Iranian folk medicine. The aqueous and ethanolic extracts were studied in mice for their ability to inhibit gastric lesions induced by HCl or absolute ethanol. In addition, their effects on gastric acid secretion were measured. Both extracts showed a dose-dependent reduction in severity of ulcers. The highest dose of extracts exerted similar activity to sucralfate. The oral and intraperitoneal administration of extracts reduced the gastric acidity in pylorus-ligated mice. These results suggest that Portulaca oleracea has gastroprotective action and validates its use in folk medicine for gastrointestinal diseases.     

Symptoms and signs of primary melanoma: important indicators of Breslow depth

BACKGROUND: Operative management of patients with cutaneous melanoma is guided primarily by the pathologic determination of Breslow depth. Differentiating early from more advanced melanoma is not always straightforward and may be complicated by pathologic misdiagnosis, inappropriate biopsy techniques, or poor specimen handling. Inconsistencies between the patient's history and the pathologist's interpretation may alert the physician to the possibility of misdiagnosis. In this setting, awareness of the signs and symptoms (S/S) of thin versus intermediate or deep melanoma may be helpful in guiding management. The authors performed a prospective evaluation of the S/S reported by patients who presented at Memorial Sloan-Kettering Cancer Center with invasive primary melanoma. METHODS: The authors prospectively evaluated 369 patients with a detailed questionnaire regarding their S/S at the time of their initial visit. Multivariate logistic regression was employed to study the association between S/S reported by the patient and Breslow depth of the primary lesion, adjusting for gender, age, and anatomic site. Patients were grouped by the Breslow depth of their primary tumors into three categories for analysis: those with thin (< or = 1.0 mm), intermediate (1.0-4.0 mm), and thick (> or = 4.0 mm) lesions. RESULTS: Gender, age, and primary site were not significantly predictive of increasing category of Breslow depth. Most patients reported at least one S/S (n=278 [75%]). The most common S/S reported was an increase in size (n=187 [51%]), followed by a change in color (n=147 [40%]). Bleeding (n=95 [26%]), lump (n=86 [23%]), itching (n=83 [22%]), skin breakdown (n=66 [18%]), and pain (n=24 [7%]) were less common. In a multivariate analysis, the S/S most strongly associated with an increased category of Breslow depth was bleeding (odds ratio [OR] 7.5), followed by pain (OR 3.3), lump (OR 2.2), itching (OR 1.9), and change in size (OR 1.7). The only S/Ss not independently associated with an increasing category of Breslow depth were a change in color and skin breakdown. The presence of one or more S/S was associated significantly with an increased category of Breslow depth of the primary melanoma (1 or 2 S/S vs. no S/S: OR, 4; > or= 3 S/S vs. no S/S: OR, 24). CONCLUSION: Most S/Ss of cutaneous melanoma are associated with an increasing risk of a deep primary lesion. Understanding this relationship can be valuable in patient management, especially when pathologic data are incomplete or inconsistent with the patient's history.     

Feasibility, acceptability and cost of home-based HIV testing in rural Kenya

Objective  To demonstrate the feasibility, acceptability and cost of home-based HIV testing and to examine the applicability of the model to high HIV prevalence settings.
Methods  Quantitative, qualitative and cost data were collected during a home-based HIV testing program in a high-prevalence rural area of Kenya; data on age, gender and marital status along with HIV test results were collected. This was complemented with qualitative research including key informant interviews with counselors and program managers to highlight experiences and challenges. Direct costs of the interventions were estimated through the review of budgets and monthly expenditure sheets.
Results  Of 3180 15–49-year olds exposed to a community awareness campaign, 2033 (63.9%) agreed to be visited by counselors, of whom 1984 (97.6%) agreed to be tested and receive the results. Adult HIV prevalence was 8.2% and married women were 4.8 times more likely to be HIV-positive than those never married. Counselors reported feeling welcomed and noted the enthusiasm of the community towards testing. The total cost of the exercise was $17 569. The program cost was $2.60 for each of the 6750 community members, $5.88 for each person tested, and $84 per positive case detected.
Conclusion  This study suggests that home-based HIV testing is feasible with high uptake, and has the potential to substantially expand access to HIV testing services. There is a strong economic case for the extension of such a screening program to other communities.     

Cannabinoids attenuate cancer pain and proliferation in a mouse model

We investigated the effects of cannabinoid receptor agonists on (1) oral cancer cell viability in vitro and (2) oral cancer pain and tumor growth in a mouse cancer model. We utilized immunohistochemistry and Western blot to show that human oral cancer cells express CBr1 and CBr2. When treated with WIN55,212-2 (non-selective), ACEA (CBr1-selective) or AM1241 (CBr2-selective) agonists in vitro, oral cancer cell proliferation was significantly attenuated in a dose-dependent manner. In vivo, systemic administration (0.013 M) of WIN55,212-2, ACEA, or AM1241 significantly attenuated cancer-induced mechanical allodynia. Tumor growth was also significantly attenuated with systemic AM1241 administration. Our findings suggest a direct role for cannabinoid mechanisms in oral cancer pain and proliferation. The systemic administration of cannabinoid receptor agonists may have important therapeutic implications wherein cannabinoid receptor agonists may reduce morbidity and mortality of oral cancer.     

Cannabinoids attenuate cancer pain and proliferation in a mouse model

The foot sole is loaded during stance and gait and plantar cutaneous mechanoreceptors sense the local stress distribution. It is not clear whether the perception thresholds of these mechanoreceptors change during the day and how they respond to walking activities. The primary aim of the present study was to investigate diurnal changes of plantar sensitivity. Furthermore, the aim was to find out whether daily changes depend on the individual level of step activity. Twenty-six healthy subjects, 17 women and 9 men, aged 28.6 ± 6.7 years participated in the study. Detection thresholds to light touch were measured in six plantar regions with Semmes-Weinstein monofilaments in the morning, noon and afternoon. Step activity was recorded with a StepWatch™ Activity Monitor and analyzed for three periods (8 a.m.-4 p.m., 8 a.m.-12 p.m., 12 p.m.-4 p.m.). The hallux, the 3rd metatarsal head and the heel showed significantly decreased detection thresholds from 8 a.m. to 4 p.m. (p ≤ 0.05). A fair correlation between the decrease of detection threshold and the total number of steps was found for the 3rd metatarsal head and the heel (p ≤ 0.05). Foot sole sensation appears to improve during the day and seems to be associated with the step activity. This may reflect an improving transfer of afferent information to the central nervous system during the day as well as an adaptation of receptors to gait activity.     

Synthesis,Antileishmanial Activity and Molecular Docking Study of New 3,4-Dihydropyrimidinones/Thiones

Pharmaceutical Chemistry Journal - Appearance of drug-unresponsive strains of Leishmania genus and toxic side effects of current chemotherapies necessitate the search for novel antileishmanial...