Spirometric Criteria for Chronic Obstructive Pulmonary Disease in Clinical Trials of Pharmacotherapy

Clinical trials of pharmacotherapy in chronic obstructive pulmonary disease (COPD) often include older persons with moderate-to-severe airflow-obstruction, as defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD). In this context, spirometric airflow-obstruction establishes COPD. Because GOLD misidentifies COPD and its severity in older persons, we set out to apply more age-appropriate spirometric criteria from the Global Lung function Initiative (GLI) in a prior clinical trial of COPD pharmacotherapy, specifically the Towards a Revolution in COPD Health (TORCH) trial — N = 6,112, mean age 65 years. In the TORCH trial, which enrolled GOLD-defined moderate COPD (26.2%, n = 1,200) and GOLD-defined severe COPD (73.8%, n = 4,511), the GLI reclassification yielded a higher frequency of severe COPD (89.6%, n = 5,474), the inclusion of restrictive-pattern (6.9%, n = 420) and, in turn, a very low frequency of moderate COPD (3.5%, n = 212). These GLI reclassification results suggest that GOLD-based enrollment criteria for the TORCH trial may have assembled a cohort that was: 1) less likely to respond to COPD pharmacotherapy, given the greater representation of severe COPD, very minor representation of moderate COPD, and inclusion of a non-obstructive spirometric impairment (restrictive-pattern); and 2) more likely to have medication-related adverse events, given the inappropriate use of COPD pharmacotherapy in misidentified COPD (restrictive-pattern). We therefore propose that future clinical trials of COPD pharmacotherapy should consider GLI criteria for defining COPD, including a greater representation of GLI-defined moderate COPD.     

Na,K-ATPase alpha4 isoform is essential for sperm fertility

Regulation of ion balance in spermatozoa has been shown to be essential for sperm motility and fertility. Control of intracellular ion levels requires the function of distinct ion-transport mechanisms at the cell plasma membrane. Active Na(+) and K(+) exchange in sperm is under the control of the Na,K-ATPase. Two molecular variants of the catalytic subunit of the Na,K-ATPase, α1 and α4, coexist in sperm. These isoforms exhibit different biochemical properties; however, their function in sperm fertility is unknown. In this work, we show that Na,K-ATPase α4 is essential for sperm fertility. Knockout male mice lacking α4 are completely sterile and spermatozoa from these mice are unable of fertilizing eggs in vitro. Furthermore, α4 deletion results in severe reduction in sperm motility and hyperactivation typical of sperm capacitation. In addition, absence of α4 causes a characteristic bend in the sperm flagellum, indicative of abnormal sperm ion regulation. Accordingly, α4-null sperm present increased intracellular Na(+) and cell plasma membrane depolarization. These results are unique in demonstrating the absolute requirement of α4 for sperm fertility. Moreover, the inability of α1 to compensate for α4 suggests that α4 is the Na,K-ATPase-α isoform directly involved in sperm fertility. Our findings show α4 as an attractive target for male contraception and open the possibility for the potential use of this Na,K-ATPase isoform as a biomarker for male fertility.     

Distribution of paraoxonase PON1 gene polymorphisms in Mexican populations. Its role in the lipid profile

Paraoxonase gene polymorphisms (PON1-55 and PON1-192) were determined in four Mexican populations (Mestizos, Nahuas, Teenek and Mayos) belonging to different ethnic groups. The role of these polymorphisms in the lipid profile in the Mestizo group was also analyzed. PON1 polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. Comparison among Mexican populations showed increased frequencies of PON1-55 L allele and LL genotype and decreased frequencies of M allele and LM genotype in the three Amerindian populations when compared to Mestizos (P < 0.05). Mexicans together with Asian populations (from Japan and China) presented the highest frequencies of PON1-55 L allele (P < 0.05 when compared to Caucasian populations). Heterogeneous data were noted when PON1-192 polymorphism comparison was made. In summary, distribution frequencies of PON1 showed that Mexican populations are more related to Asians than Caucasians. This confirms previous studies with other genetic markers indicating that Native Americans have stronger genetic affinities to the Paleolithic people of North-East Asia than to other major world populations. In Mexican Mestizos, lack of correlation between PON1 polymorphisms and lipid profile was found, corroborating previous data in other populations. The present data could be helpful to understand the distribution of these polymorphisms and its role as genetic and evolutive markers in the Amerindian populations.     

Literature systematic review on the ophthalmological side effects of interferons

Interferons alpha and beta have been used worldwide for a few decades, altering the natural history of several severe diseases including hepatitis C, cancer and immune-mediated conditions such as multiple sclerosis. The adverse events profile of interferons is well established, but only isolated reports of ophthalmological complications of interferon therapy have been published. The objective of this study was to carry out a literature systematic review on the subject, bringing to light the need for careful ophthalmological monitoring of patients undergoing interferon treatment. Nearly 500 cases of ophthalmological complications related to interferon have been reported. The most frequent findings were soft exudates, hemorrhages and retina ischemia.     

Occurrence,isolation and differentiation of Candida spp. and prevalence of variables associated to chronic atrophic candidiasis

The purpose of this study was to survey the frequency of Candida spp. in patients with chronic atrophic candidiasis (CAC), to differentiate Candida species and to assess the prevalence of certain infection‐associated variables to this disease. Patients with CAC and wearing partial or complete dentures were recruited. Data were obtained by means of a questionnaire with details involving identification of the subject, demographic characteristics, behaviour and medical history, clinical and mycological evaluation and identification of yeast. The sample collection was carried out in the palate or palate and tongue of the subjects using sterilised swabs. Data were submitted to statistical analyses using Fischer’s test. Forty‐three (53%) cases of CAC showed the presence of Candida albicans. Females (75.2%) wearing complete dentures (60.1%) for more than 10 years (58%) were risk factors to CAC development. It could be concluded that: (a) the results did not confirm a significant difference among patients with CAC concerning the presence or absence of Candida spp.; (b) the occurrence of Candida was negatively related to important factors associated to this opportunistic infection; and (c) mycological findings did not indicate that the variables investigated have a significant effect on oral infections by C. albicans or other Candida species.     

Hipofisitis linfocitaria en gestante de 34 semanas

We report the case of a 23-year-old woman at 33 + 4 weeks of pregnancy who was admitted for investigation of bitemporalhemianopsia and endocrine disruption. We discuss the main differential diagnoses by reviewing the pathophysiology of lymphocytic hypophysitis, as well as the management of this disease.     

Side‐Effects of Irinotecan (CPT‐11), the Clinically Used Drug for Colon Cancer Therapy,Are Eliminated in Experimental Animals Treated with Latex Proteins from Calotropis procera (Apocynaceae)

Intestinal mucositis (IM) is the critical side effect of irinotecan (CPT‐11), which is the front‐line drug used for the treatment of colorectal cancer. This study aimed to evaluate the effectiveness of latex proteins (LP) from Calotropis procera to prevent IM and diarrhea in animals. Swiss mice were treated daily with saline or LP (1, 5, or 50 mg/kg, i.v.) 24 h prior to CTP‐11 (75 mg/kg/4 days, i.p) and for additional 6 days. Animal survival, body weight variation, and diarrhea were registered. After animal sacrifice (day 7 post first injection of CPT‐11), intestinal samples were collected to study morphology and inflammatory parameters. Animals given LP exhibited improved parameters (survival, body weight, and absence of diarrhea) as compared with the CPT‐11 control. The severity of IM observed in animals given CPT‐11 was reduced in animals treated with LP. Treatment with LP also prevented the reduction in the villus/crypt ratio promoted by CPT‐11. The rise in MPO activity and pro‐inflammatory cytokines, over‐contractility of the smooth muscle, and diarrhea were all abrogated in LP‐treated mice. Markedly reduced immunostaining intensity for COX‐2, TNF‐α, IL‐1β, iNOS, and NF‐κB was observed in the intestinal tissue of animals treated with LP. The side‐effects of CPT‐11 were eliminated by LP treatment in experimental animals and improved clinical parameters characteristic of IM All known biochemical pathogenesis. Copyright © 2016 John Wiley & Sons, Ltd.