Anti-carbamylated protein antibodies positivity and disease activity in Hispanic patients with established rheumatoid arthritis: An observational study.

OBJECTIVES: We aimed to determine the prevalence of anti-carbamylated protein (anti-CarP) antibodies in Mexican Hispanics with established rheumatoid arthritis (RA) and to assess their relationship with disease activity. METHODS: A cohort study was conducted in 278 patients with established RA during an 18-month follow-up. We measured IgG/IgM/IgA rheumatoid factor (RF), IgG anticitrullinated protein antibodies (ACPA) and IgG/IgM/IgA anti-CarP antibodies using enzyme-linked immunosorbent assay (ELISA). For disease activity, we performed the 28-joint disease activity score with erythrocyte sedimentation rate (DAS28-ESR). Repeated measures one-way ANOVA was used to test the association between anti-CarP IgG antibody status and longitudinal DAS28-ESR scores. Patients were evaluated at baseline and at 6, 12, and 18 months during follow-up. RESULTS: Anti-CarP IgG antibodies were positive in 47.8% of patients and, accounting for all isotypes, in 9.5% of patients with negative RF and ACPA. Triple antibody positivity was present in 42.6% of patients in our sample. Anti-CarP IgG antibody positivity did not show statistically significant differences in mean DAS28-ESR when compared to anti-CarP IgG antibody negative patients at baseline, 6, 12 or 18 months. CONCLUSION: Anti-CarP IgG antibodies are not associated to a higher disease activity in Hispanic patients with established RA. Our findings suggest that the clinical value of measuring anti-CarP antibodies in RA diminishes over time.

Stereochemistry of a Second Riolozane and Other Diterpenoids from Jatropha dioica.

The dichloromethane extract of the roots of Jatropha dioica afforded riolozatrione (1) and a C-6 epimer of riolozatrione, 6-epi-riolozatrione (2), as a new structure and only the second reported riolozane diterpenoid. The two known diterpenoids jatrophatrione (3) and citlalitrione (4) were also isolated and characterized. Both epimers 1 and 2 are genuine plant constituents, with 2 likely being the biosynthesis precursor of 1 due to the tendency for the quantitative transformation of 2 into 1 under base catalysis. The structural characterization and distinction of the stereoisomers utilized 1H iterative full-spin analysis, yielding complete J-correlation maps that were represented as quantum interaction and linkage tables. The absolute configuration of compounds 1-4 was established by means of vibrational circular dichroism and via X-ray diffraction analysis for 1, 2, and 4. Additionally, the cytotoxic and antiherpetic in vitro activities of the isolates were evaluated.

Immunomodulatory activity of diethylcarbamazine on humoral, cellular cytokine response and respiratory burst in BALB/c mice.

Diethylcarbamazine (DEC) is an anthelmintic piperazine derivative drug with putative immunomodulating properties, including increased platelet and granulocyte adhesion to parasites and enhanced production of cytokines. To further analyse these properties in a well-established animal model, we evaluated the effect of DEC on antibody, cellular cytokine response and respiratory burst in BALB/c mice. Animals were challenged with a thymus-dependent (tetanus toxoid, (TT)) and with a thymus-independent (lipopolysaccharide, (LPS)) antigen and treated with DEC for seven days with two different doses (50 mg/day and 500 mg/day). Serum was assessed for antibody production at 0, 4, 7, 14, 21 and 28 days after stimulation and at 0, 24 and 48 h for IL-2, IFN-γ, IL-10 and IL-12 release. Respiratory burst of neutrophils and monocytes from peripheral blood was measured by flow cytometry. We found low-dose treatment with DEC enhanced cytokine production vs. TT and antibody production vs. LPS, whereas a higher dose enhanced significantly the respiratory burst of both polymorphonuclear leukocytes and monocytes, with a significant higher effect on the former. Our results suggest a stimulating, dose-dependent immunomodulatory effect of DEC with a higher effect on the phagocytic cells.

Evidence for differences in immunologic and pathogenesis properties of herpes simplex virus 2 strains from the United States and South Africa.

BACKGROUND: Genital infection with herpes simplex virus 2 (HSV-2) is linked to an increased risk of infection with human immunodeficiency virus (HIV) in areas such as Sub-Saharan Africa. Thus, an effective genital herpes vaccine would be an important weapon in the fight against HIV/AIDS. METHODS: To test whether a current vaccine candidate can protect against HSV-2 from Sub-Saharan Africa, we examined the ability of an HSV-2 vaccine strain, dl5-29, and other HSV-2 replication-defective mutant strains to protect against genital challenge with US or South African strains in a murine model. RESULTS: Immunization with dl5-29 reduces infection by both viruses but is significantly more efficacious against the US virus than against the African virus. Furthermore, another US vaccine strain was more efficacious against US than against African viruses, and the converse was observed for the parallel African vaccine strain. Nevertheless, protection against the African viruses was significantly less with all vaccines used in this study. CONCLUSIONS: We conclude that there may be differences in protective epitopes and pathogenesis between the US and African strains that raise the need for increased doses of the existing vaccine candidate or an HSV-2 vaccine strain based on viruses from that region.

Screening of north-east Mexico medicinal plants with activities against herpes simplex virus and human cancer cell line.

The plants examined in this study have previous biological activity reports indicating the possibility of found activity against herpes and cancer cell. The aim of this contribution was to carry out a screening of Juglans mollis (Juglandaceae), Persea americana (Lauraceae), Hamelia patens (Rubiaceae), Salvia texana (Lamiaceae), Salvia ballotaeflora (Lamiaceae), Ceanothus coeruleus (Rhamnaceae), Chrysactinia mexicana (Asteraceae) y Clematis drummondii (Ranunculaceae), against HeLa cells, VHS-1 and VHS-2. The method MTT was used to determine the 50% cytotoxic concentration (CC50), in Vero and HeLa cell lines. To determine the 50% inhibitory concentration (IC50) against herpes, the plaque reduction method was used. Results showed that none of the plants exhibited activity against HeLa cells. About antiherpetic activity, J. mollis and S. ballotaeflora extracts present antiherpetic activity in terms of their SI, increasingly interest for further studies on the isolation of compounds with antiherpetic activity and about the mechanisms of action that produce this activity.

[Perfil de expresión de Ki67 en lesiones melanocíticas palmoplantares: estudio de casos y controles]. / Expression profile of Ki67 in palmoplantar melanocytic lesions: a case-control study.

INTRODUCCIÓN: El melanoma acral lentiginoso es una neoplasia maligna que afecta a población predominantemente no caucásica. Debido al diagnóstico tardío suele tener mal pronóstico, además de que se considera una neoplasia biológicamente más agresiva, incluso cuando se detecta tempranamente. OBJETIVO: Determinar la expresión de Ki67 en el melanoma acral lentiginoso invasor y compararla con los nevos acrales. MÉTODO: Estudio transversal, descriptivo, observacional. Se realizó inmunohistoquímica con marcador Ki67 en 17 biopsias de melanoma acral lentiginoso invasor (casos) y 17 biopsias de nevos palmoplantares (controles). Se determinó la expresión nuclear de Ki-67 y se comparó entre ambos grupos. RESULTADOS: La media de expresión de Ki67 fue del 8.5% en el grupo control y del 34% en el grupo de melanomas, siendo esta diferencia estadísticamente significativa (p < 0.0001). DISCUSIÓN: La expresión de Ki67 en los melanomas acrales es considerablemente mayor que en los nevos acrales. El valor pronóstico del marcador Ki67 sigue siendo considerado controversial. Sin embargo, hay estudios en los que en combinación con otros marcadores se refuerza su valor pronóstico. CONCLUSIONES: Por la gran diferencia en inmunorreactividad de Ki67 entre melanomas y nevos, la expresión de Ki67, referida como índice proliferativo, podría ser considerada como factor pronóstico incluso más objetivo que el índice mitótico. BACKGROUND: Acral lentiginous melanoma is a malignant neoplasm which appears in hands and feet. Acral lentiginous melanoma has an unclear etiology, and usually affects non-Caucasian population. Because it is frequently diagnosed lately, acral melanoma has bad prognosis; however, it is biologically more aggressive than other clinicopathological types of melanoma, even when diagnosed early. OBJECTIVE: To determine the expression of Ki67 in invasive lentiginous acral melanoma and to compare it with acral nevi. METHOD: Cross-sectional, descriptive, observational study. Immunohistochemistry with Ki67 marker was performed on 17 biopsies of invasive lentiginous acral melanoma (cases) and 17 biopsies of palmoplantar nevi (controls). Nuclear expression of Ki-67 was determined and both were compared between both groups. RESULTS: The mean expression of Ki67 was 8.5% in the control group, and 34% in the melanoma group, which was statistically significant (p < 0.0001). DISCUSSION: Ki67 expression in acral lentiginous melanomas is higher than in acral nevi. Prognostic value of Ki67 is still considered controversial. However, there are several studies where, in combination with other markers, their prognostic value is reinforced. CONCLUSIONS: Due to the wide gap in Ki67 expression between melanomas and nevi showed in this study, Ki67 expression, referred to as a proliferative index, could be considered as a prognostic factor even more objective than the mitotic index.

Antiherpetic Plants: A Review of Active Extracts, Isolated Compounds, and Bioassays.

Herpes simplex is a disease that is widely distributed throughout the world. It is caused by herpes simplex virus type 1 (HSV-1) and simplex virus type 2 (HSV-2). The drugs of choice for treatment are acyclovir (ACV), Penciclovir (PCV) and other guanine analogues, which have the same mechanism of action. However, due to the constant increase of ACV-resistant strains in immunocompromised patients, it is necessary to find new treatment alternatives. It has been shown that natural products are a good alternative for the treatment of these diseases as well as being an excellent source of compounds with anti-herpetic activity, which may be useful for the development of new drugs and act through a mechanism of action different from ACV and PCV. This paper compiles reports on extracts and compounds isolated from plants that have anti-herpetic activity. We present an analysis of the solvents most widely used for extraction from plants as well as cells and commonly used methods for evaluating cytotoxic and anti-herpetic activity. Families that have a higher number of plants with anti-herpetic activity are evaluated, and we also highlight the importance of studies of mechanisms of action of extracts and compounds with anti-herpetic activity.

Plants from northeast Mexico with anti-HSV activity.

Based on chemotaxonomic and ethno-pharmacological criteria, three Mexican plants (Jatropha dioica, Salvia texana and S. ballotaeflora) were studied for in vitro activity against HSV-1 and HSV-2. Hydro-methanolic extracts were initially evaluated for their toxicity to Vero cells. Both Salvia species displayed cytotoxicity at the lowest dose (125 microg/mL). The J. dioica extract showed only negligible cytotoxicity (CC50 644 microg/mL). Its anti-HSV activity was evaluated using the plaque reduction assay with HSV-1 and HSV-2 (from clinical isolates) infected Vero cells. The hydro-methanolic extract of J. dioica showed IC50s of 280 and 370 microg/mL against HSV-1 and HSV-2, respectively. The n-hexane liquid-liquid partition of J. dioica extract contained the majority of the active principle(s) with IC50 values of 300 and 270 microg/mL for HSV-1 and HSV-2, respectively. Bioassay-guided isolation led to the known diterpene, riolozatrione.

Expression of leptin receptor in endometrial biopsies of endometrial and ovarian cancer patients.

The adipokine leptin plays a critical role in the regulation of reproductive function and there has been growing interest in its potential role in the development of cancers in which obesity is an established risk factor. Serum leptin levels were found to be higher in patients diagnosed with endometrial and ovarian cancer compared to those observed in healthy individuals. This study was conducted to determine the expression of the leptin receptor (Ob-R) in endometrial biopsies of patients diagnosed with endometrial and ovarian cancer. In this preliminary study, immunohistochemistry (IHC) and the color deconvolution method were used to assess the expression levels of the Ob-R protein in three groups of endometrial tissue: one from patients diagnosed with endometrioid endometrial carcinoma, one from patients diagnosed with ovarian cancer and one from individuals without any diagnosed gynecologic disease (control group). Our results demonstrated that the highest expression of Ob-R protein in endometrial biopsies was detected in the ovarian cancer group (P=0.000). This finding suggests that changes in Ob-R expression may be assessed through the measurement of the optical density of endometrial biopsies and may become a useful tool in preventive screening, particularly for ovarian cancer.

Immunization with a replication-defective herpes simplex virus 2 mutant reduces herpes simplex virus 1 infection and prevents ocular disease.

Ocular infections with herpes simplex virus 1 can lead to corneal scarring and blindness, with herpes keratitis being the major infectious cause of blindness. There is currently no clinically approved vaccine and nearly all developmental vaccines are targeted against HSV-2 and genital herpes. We tested the ability of an HSV-2 replication-defective virus, a genital herpes vaccine candidate, to protect against HSV-1 corneal infection. Immunization with HSV-2 dl5-29 reduced viral replication in the cornea, prevented ocular disease and reduced latent infection by the HSV-1 strain. Therefore, this HSV-2 replication-defective mutant strain may have applications for prevention of herpes keratitis and genital herpes due to HSV-1 infection.