Background The prevalence of comorbidities and their relation to asthma control and treatment is a topic of increasing interest, however comprehensive studies are scarce. We aimed to determine the prevalence of the most common comorbidities in asthma in relation to patient characteristics (age, gender and body mass index [BMI]) and their association with asthma control in a large, specialist-managed representative patient population. Methods A secondary, exploratory analysis of the Asthma Reality (ARL), across-sectional, non-interventional real-life study was conducted. Basic patient characteristics, the prevalence of comorbidities and data on asthma control and risk factors had been collected and their interactions examined. Descriptive statistics and binomial regression were used to assess the distribution of the prevalence of comorbidities and propensity matching was applied to assess their effect on asthma control. Results Overall, 12,743 patients were enrolled in our study in 187 treatment centres covering all regions of Hungary. Most comorbidities showed significantly different distribution for all basic patient characteristics. Gender, age group, smoking status, BMI and the duration of asthma had a significant impact on asthma control. The frequency of uncontrolled asthma was higher in females (37.1%), in the age group of 46–65 years (39.6%), in severely obese patients (43.2%), in patients who had been diagnosed with asthma for more than 20 years (40.4%), and in active heavy smokers (55%), compared with respective groups in the same category. Based on the binomial regression with propensity score matching, concomitant chronic obstructive pulmonary disease (COPD) (odds ratio [OR] = 2.06, 95% confidence interval [CI] 1.80–2.36), ischaemic heart disease (OR = 1.86, 95% CI 1.64–2.10) and cerebrovascular events (OR = 1.85, 95% CI 1.47–2.32) had the strongest negative effect on asthma control, with the presence of all of these conditions increasing the risk of uncontrolled asthma. Conclusions This evaluation of comorbidity data of more than 12,000, adult asthmatic patients has provided a clearer picture of diseases that can frequently co-exist with asthma, and their influence on asthma control, assessed by the prevalence of symptoms. Our study suggests that most asthmatic patients have at least one comorbidity, and the presence of comorbidities may have a high impact on asthma control measures.

New Vinca alkaloid derivatives were synthesized to improve the biological activity of the natural alkaloid vindoline. To this end, experiments were performed to link vindoline with various structural units, such as amino acids, a 1,2,3-triazole derivative, morpholine, piperazine and N-methylpiperazine. The structure of the new compounds was characterized by NMR spectroscopy and mass spectrometry (MS). Several compounds exhibited in vitro antiproliferative activity against human gynecological cancer cell lines with IC50 values in the low micromolar concentration range.

Some Vinca alkaloids (eg, vinblastine, vincristine) have been widely used as antitumor drugs for a long time. Unfortunately, vindoline, a main alkaloid component of Catharanthus roseus (L.) G. Don, itself, has no antitumor activity. In our novel research program, we have prepared and identified new vindoline derivatives with moderate cytostatic activity. Here, we describe the effect of conjugation of vindoline derivative with oligoarginine (tetra-, hexa-, or octapeptides) cell-penetrating peptides on the cytostatic activity in vitro and in vivo. Br-Vindoline-(l)-Trp-OH attached to the N-terminus of octaarginine was the most effective compound in vitro on HL-60 cell line. Analysis of the in vitro activity of two isomer conjugates (Br-vindoline-(l)-Trp-Arg and Br-vindoline-(d)-Trp-Arg suggests the covalent attachment of the vindoline derivatives to octaarginine increased the antitumor activity significantly against P388 and C26 tumour cells in vitro. The cytostatic effect was dependent on the presence and configuration of Trp in the conjugate as well as on the cell line studied. The configuration of Trp notably influenced the activity on C26 and P388 cells: conjugate with (l)-Trp was more active than conjugate with the (d)-isomer. In contrast, conjugates had very similar effect on both the HL-60 and MDA-MB-231 cells. In preliminary experiments, conjugate Br-vindoline-(l)-Trp-Arg exhibited some inhibitory effect on the tumor growth in P388 mouse leukemia tumor-bearing mice. Our results indicate that the conjugation of modified vindoline could result in an effective compound even with in vivo antitumor activity.

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10-Aminovindoline and 17-desacetylvindoline were coupled with 5α- dihydrotestosterone hemisuccinate and 19-nortestosterone hemisuccinate. As a result, four vindoline-steroid hybrids were synthesized via a succinate linker. One of the new hybrid compounds showed significant anticancer effect in vitro in the case of colon cancer and melanoma cell lines.