Partition coefficient determination of a series of isoindolines-2-substituted and its correlation with their antiproliferative activity on HeLa cells

In this study, the partition coefficients (Log P) of two series of isoindolines-2-substituted were calculated from the equation obtained for the multilinear correlation between the electronic properties: the highest occupied molecular orbital and the lowest unoccupied molecular orbital energies, and the steric property volume, and the experimental Log P values were determined for some representative isoindolines. Log P values calculated under quantum chemistry were compared with Log P values obtained by the Log P calculation software ALOGPS 2.1 server; the Log P values calculated showed a better correlation with experimental Log P values than those obtained by means of the software. Log P values calculated were also correlated with the antiproliferative activity of some isoindolines-2-substituted determined on HeLa cells, and the correlation obtained shows a quadratic relationship between Log P values calculated and the antiproliferative activity of isoindolines-2-substituted, suggesting a significant effect of Log P values on biological activity of isoindolines.     

Breast cancer mortality trends in Mexico, 1980-2009

Breast cancer has become an important health risk for women worldwide.The important growth of breast cancer-related deaths within those caused by malign tumors throughout the globe went past the 460 000 in 2008,becoming the deadliest disease worldwide. Demographic changes and lifestyles have modified the population exposure to risk factors of maladies such as cancer, and since 1980 breast cancer mortality has remained on an upward tendency, surpassing cervical cancer in 2006. After analyzing mortality rates along 30 years in Mexican women 25 or more years old, differences by state and age-groups are apparent. Although this cause of death has been associated with a highest regional development, some changes are taking place,since the number of deaths is also growing among women of less-developed regions in the country,as showed in this work. Mexico faces an evident challenge regarding breast cancer. Our country requires to join efforts and implement programs aimed at teaching self-care of health among the population,promoting healthier lifestyles, and reshaping our diagnostic infrastructure to achieve earlier detection and provide proper treatment.     

Evolution of hepatitis C viral quasispecies and hepatic injury in perinatally infected children followed prospectively

Perinatal infection with hepatitis C virus (HCV) is characterized by a wide range of alanine aminotransferase (ALT) levels. The mechanisms responsible for this variability are unknown. We examined whether the evolution of the HCV quasispecies was associated with different ALT profiles in perinatally infected children. Sequences within HCV envelope 1 and 2 genes, inclusive of the hypervariable region 1, the viral load, and the nascent humoral immunity were analyzed in serial serum samples from 12 perinatally infected children prospectively followed for a median of 53 months. These patients were selected to represent two different ALT patterns during the first year of life: 6 had high levels (maximum values ranging from 4.2 to 30 times the normal upper limit), and 6 had normal or slightly elevated levels (< 2 times the normal upper limit). Two patterns of viral evolution were identified according to the ALT profiles. Biochemical evidence of hepatic injury was invariably associated with a mono- or oligoclonal viral population, whereas mild or no liver damage correlated with the early emergence of a heterogeneous viral quasispecies. Consistent with selective immune pressure, amino acid changes occurred almost exclusively within the hypervariable region 1 and were temporally associated with antibody seroconversion; at this time, the difference in genetic diversity between the two groups was highly significant (P = 0.002). The two patterns of viral evolution persisted over time and did not correlate with viral load or genotype. Our study demonstrates that, in perinatally infected children, the evolution of HCV quasispecies correlates with hepatic injury. The sequences reported in this paper have been deposited in the GenBank database (accession nos. DQ 504441-DQ 507112).     

In vivo induction of phase II detoxifying enzymes, glutathione transferase and quinone reductase by citrus triterpenoids

Background  

Several cell culture and animal studies demonstrated that citrus bioactive compounds have protective effects against certain types of cancer. Among several classes of citrus bioactive compounds, limonoids were reported to prevent different types of cancer. Furthermore, the structures of citrus limonoids were reported to influence the activity of phase II detoxifying enzymes. The purpose of the study was to evaluate how variations in the structures of citrus limonoids (namely nomilin, deacetyl nomilin, and isoobacunoic acid) and a mixture of limonoids would influence phase II enzyme activity in excised tissues from a mouse model.     

Comparative Evaluation of Lesion Development,Tissue Damage,and Cytokine Expression in Golden Hamsters (Mesocricetus auratus) Infected by Inocula with Different Leishmania (Viannia) braziliensis Concentrations

The golden hamster (Mesocricetus auratus) is a susceptible model to Leishmania (Viannia) spp.; however, available studies employ different infection protocols, which account for clinical and pathological presentation differences. Herein, L. (V.) braziliensis preparations were standardized to contain 10⁴, 10⁵, or 10⁶ parasites to determine an optimal inoculum that ensured cutaneous lesions without causing a disseminated infection in hamsters. Lesion development was followed for 105 days by size measurements, and skin, draining lymph node, spleen, and sera were investigated to check parasite load, spleen visceralization, cytokine expression, histopathological changes, and anti-Leishmania IgG levels. The lesion emergence time was inversely proportional to the parasite concentration in the inocula. Animals infected by 10⁴ parasites presented nodular lesions, while those infected with 10⁶ parasites often exhibited ulcerated lesions. The differences in the final lesion sizes were observed between 10⁴ and 10⁵ inocula or 10⁴ and 10⁶ inocula. High IFNG expression, anti-Leishmania IgG levels, and parasite load occurred independently of the inoculum used. A mild inflammatory skin involvement was observed in animals infected with 10⁴ parasites, while extensive tissue damage and parasite spleen visceralization occurred with 10⁵ and 10⁶ parasites. These results indicate that inocula with different concentrations of parasites generate differences in the time of lesion emergence, clinical presentation, and systemic commitment, despite high and similar IFNG expression and parasite load. This suggests that a modulation in the immune response to different parasite numbers occurs in an early phase of the infection, which could dictate the establishment and magnitude of the chronic phase of the disease.     

Epidemiology and control of intestinal parasites with nitazoxanide in children in Mexico

The purpose of this study was to evaluate the efficacy and the tolerance of nitazoxanide in children as a single broad-spectrum antiparasitic agent in the treatment of mixed parasite infections with both intestinal protozoa and helminths. Two hundred seventy-two children (age range = 2-14 years) participated in this study. We systematically surveyed every household head using questionnaires designed to obtain information about household socioeconomic status and hygiene. Parasitic infections were confirmed by three stool examinations using direct smear, Ferreira concentration, and cold acid-fast Kinyoun staining methods. One hundred twenty-one (44%) children tested positive for protozoa such as Giardia lamblia (18%), Entamoeba histolytica/E. dispar (10%), Blastocystis hominis (7%), Cryptosporidium parvum (4%), and Cyclospora cayetanensis (3%), and helminths such as Hymenolepis nana (10%), Trichuris trichiura (6%), and Ascaris lumbricoides (6%). There were also two cases of infection with Enterobius vermicularis. After a complete physical examination was performed, 121 patients received treatment with nitazoxanide. Overall, 84% of the protozoa and 95% of the helminths were completely eliminated from the patients. Nitazoxanide was very well tolerated, with no serious adverse effects reported.     

Consequences of low plasma histidine in chronic kidney disease patients: associations with inflammation, oxidative stress, and mortality

BACKGROUND: Histidine is considered as an antiinflammatory and antioxidant factor. Histidine deficiency may contribute to an impaired nutritional state in patients with chronic kidney disease (CKD). OBJECTIVE: We aimed to investigate the consequences of plasma histidine deficiency in CKD patients. DESIGN: CKD patients (n = 325; 203 M) with a median age of 54 y (range: 19-70 y) were evaluated shortly before the beginning of renal replacement therapy. The median glomerular filtration rate was 6.4 mL/min (range: 0.8-14.5 mL/min). Nutritional status was assessed by subjective global assessment. Survival was followed for up to 60 mo; 101 patients died. RESULTS: Plasma histidine concentrations were significantly lower in CKD patients with history of cardiovascular disease, presence of plaques, protein-energy wasting, and inflammation. Plasma histidine was negatively associated with age, C-reactive protein, interleukin-6, leukocytes, thrombocytes, fibrinogen, hepatocyte growth factor, adhesion molecules, insulin-like growth factor-1, and 8-hydroxy-2'-deoxyguanosine and was positively associated with handgrip strength, hemoglobin, S-albumin and fetuin-A. A multivariate regression analysis showed that histidine concentrations were independently associated with hepatocyte growth factor, hemoglobin, and fetuin-A. In unadjusted analysis, a low histidine concentration was associated with all-cause mortality (log rank chi-square test = 8.9; P = 0.002). After adjustment for age, sex, cardiovascular disease, inflammation, diabetes mellitus, serum S-albumin, and amino acid supplementation, the association between low histidine and mortality remained significant (hazard ratio: 1.55; 95% CI: 1.02, 2.40; P < 0.05). CONCLUSION: Low plasma concentrations of histidine are associated with protein-energy wasting, inflammation, oxidative stress, and greater mortality in CKD patients.     

Organizational stress and noise exposure in workers at the packing plant of a brewer factory

The purpose of this study was to identify and to evaluate the psychosocial factors that produce organizational stress in workers at the packing plant of a brewering industry, and to determine the influence of industrial noise in the occurrence of stress at work. The Questionnaire of Organizational Stress of the ILO/WHO was applied to 163 workers to evaluate psychosocial factors at work, and the socio-demographic characteristics were explored on an individual basis. The equivalent continuous sound level (Leq) was determined and the octave band were determined with a sonometer according to the COVENIN guidelines. Total stress was found in 55 workers (33.74%). Of those, 42 workers were in an intermediate level (25.76%) and 13 workers (7.98%) were in the stress level (p < 0.0001). The occurrence of pondered stress was 100%, classified as: influences of the leader (14.00 +/- 7.27; 87.7%), organizational structures (12.36 +/- 5.14; 93.3%) and organizational climate (11.83 +/- 5.09; 95.1%). The mean of total and pondered stress showed an upward tendency as age and labor antiquity increased (p < 0.05). Leq was in a range of 87.9-100 dB(A), which exceeds the threshold value limit. There was no association between Leq was stress. The level of total stress that these workers perceive is similar to that described in other studies. The pondered stress becomes a highly sensitive variable to determine which psychosocial factors produce stress. This can be used for implementing control and preventive measures of organizational stress.     

Rationale of the Combined Use of Inspiratory and Expiratory Devices in Improving Maximal Inspiratory Pressure and Maximal Expiratory Pressure of Patients With Chronic Obstructive Pulmonary Disease

Battaglia E, Fulgenzi A, Ferrero ME. Rationale of the combined use of inspiratory and expiratory devices in improving maximal inspiratory pressure and maximal expiratory pressure of patients with chronic obstructive pulmonary disease.

Objective

To examine the rationale of the combined use of a new expiratory device in association with a previously assessed inspiratory device in improving 3 indicators of the respiratory muscle strength, for example, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and dyspnea grade.

Design

Randomized trial.

Setting

Home-based pulmonary rehabilitation.

Participants

Adults (N=32; mean age, 68y).

Main Outcome Measure

We instructed 32 patients with mild to very severe COPD to use the devices, and randomized them in a 1:1 ratio: they were assigned to the sham training control group (16 patients who trained at a load not able to improve MIP and MEP) or to the training group (16 patients). The patients trained at home twice daily for 15 minutes, 7 days a week, for 12 months. MIP and MEP as well as dyspnea perception were evaluated at 1, 6, and 12 months from the beginning of the training. The impact of additional work of breathing was measured at baseline and after the use of the expiratory device.

Results

The patients who performed the respiratory training showed significant and progressive improvements of MIP (81±4 at 12 months vs 57±7 as basal values expressed in cm H₂O; P<.05) and MEP (97±2 at 12 months vs 62±4 as basal values; P<.05) at the end of the training. In addition, they showed a significant reduction of dyspnea perception (1.18±0.29 vs 2.93±0.32 as basal values; P<.05) at the end of the training.

Conclusions

This study suggests that home exercise with the combined use of our expiratory and inspiratory devices leads to a significant improvement of respiratory muscle function in patients with mild to very severe COPD.