Antitumor activity of novel <Emphasis Type="Italic">N</Emphasis>-sulfonylpyrimidine derivatives on the growth of anaplastic mammary carcinoma in vivo

Purpose: The purpose of this study was to investigate in vivo antitumor activity of newly synthesized N-sulfonylpyrimidine derivatives 1-(p-toluenesulfonyl)cytosine (4H), 1-(p-toluenesulfonyl)cytosine hydrochloride (4H×HCl) and zinc(II) complex of 1-(p-toluenesulfonyl)cytosine (4K). Materials and methods: In order to do that we have used mouse anaplastic mammary carcinoma (AMCa). Tumor cells (10⁶) in a volume of 0.02 ml were transplanted into the thigh of the right hind leg of CBA mice. All compounds were dissolved in distilled water immediately before injecting to animals. Results: Antitumor effect of these compounds depends on drug doses and time interval between tumor transplantation and drug application. Further the efficacy of these compounds depends on number of drug injections, i. e. whether drug was given in single or in multiple doses. Multiple doses of 400 mg/kg of 1-(p-toluenesulfonyl)cytosine (4H) showed good antitumor effect when applied on day 1, 3, 5, 7 and 9 after tumor transplantation. Still good but slightly lower antitumor effect was also achieved when that compound was given in a single dose (1,200 mg/kg) on day 1 after tumor transplantation. The longest period of tumor growth time was obtained after application of 1-(p-toluenesulfonyl)cytosine hydrochloride (4H×HCl) given as a single dose (300 mg/kg) on day 1 or on day 6 after tumor implantation. However, antitumor effect of zinc(II) complex of 1-(p-toluenesulfonyl)cytosine (4K) was very strong when 300 mg/kg was given on day 1 or day 6, while this effect was slightly lower when drug (200 mg/kg/inj) was given on day 1, 3, 5, 7 and 9 or on day 6, 8, 10, 12 and 14. Conclusion: In this work it has been found that N-1-sulfonylcytosine derivatives have strong antitumor activity against mouse mammary carcinoma which is a good reason for further research of these compounds both in experimental and preclinical studies.     

Dental and Skeletal Age in Patients with Palatally Displaced Canines

ObjectiveTo determine potential associations between dental and skeletal maturation and palatally displaced canines (PDC) considering gender and chronological age.Material and methodsThis study included pretreatment panoramic and lateral cephalometric radiographs of 43 subjects with PDCs and 203 randomly selected orthodontic subjects with normally erupted canines. Both groups were non syndromic patients. Chronological age of subjects was rounded and noted in years with decimal points and compared with chronological age according to Demirjian''s dental age assessment. Skeletal maturation was determined by cervical vertebrae changes on cephalometric radiographs.ResultsFemale subjects with PDC were more affected by left side canine displacement than males (p=0.027) with five times higher odds ratio (OR = 4.9; 95% CIL=1.2-19.7). A comparison of chronologic and skeletal age indicated that PDC subjects were skeletally younger than unaffected groups with statistically significant differences at the age of 10, 12 and 13. (p=0.05).ConclusionYoung subjects with PDCs showed skeletal maturation delay compared to control group, indicating that skeletal maturation assessment could be one of unexplored predicting factors of a PDC, especially at the age between 10 and 13 years in both genders. Subjects with PDC showed intensive growth spurt after the age of 12 years in females, and after the age of 13 in males. Dental maturation delay showed no statistical significance in PDC prediction.     

Asthma phenotypes in childhood

Introduction: Asthma is no longer thought of as a single disease, but rather a collection of varying symptoms expressing different disease patterns. One of the ongoing challenges is understanding the underlying pathophysiological mechanisms that may be responsible for the varying responses to treatment.

Areas Covered: This review provides an overview of our current understanding of the asthma phenotype concept in childhood and describes key findings from both conventional and data-driven methods.

Expert Commentary: With the vast amounts of data generated from cohorts, there is hope that we can elucidate distinct pathophysiological mechanisms, or endotypes. In return, this would lead to better patient stratification and disease management, thereby providing true personalised medicine.     

Necrotic ulcerative stomatitis in a patient with long-standing celiac disease: a case report

Celiac disease is the most common chronic gastroenterological disease. One of the extraintestinal manifestations of this multifaceted disease are changes in the oral mucosa. However, ulceration leading to the destruction of the soft and hard tissues of the orofacial region has not been reported so far. We report on the development of necrotizing ulcerative stomatitis in a 41-year-old woman with celiac disease. The initial ulcerative lesion was located in the lower lip mucosa. Necrosis of all layers of the left side of the lip and oral commissure progressed very quickly. The resulting defect required plastic reconstructive surgery. We successfully compensated for the defect by applying a combination of two flaps from the remaining tissue of the lower lip. Oral competence was established immediately after the operation, and a very good esthetic appearance two months later.

The epidemiological link between celiac disease and oral mucosal ulcers is well known (1). Although this disease may cause malabsorption as a major factor in the development of necrotizing ulcerative stomatitis (NUS), such a case has not been reported in the literature. The onset of this infection is preceded by poor dental and gingival status accompanied by gingival ulcers and necrotic periodontitis. In patients with impaired immune system and malnutrition oral infection develops very rapidly into NUS. At this stage, the patient can develop septicemia and fatal outcome or the inflammation is defined by a well-demarcated circular defect called noma (2). NUS usually occurs in children living in poor conditions in Central African countries. In the developed world today, it is encountered sporadically, most often in seropositive HIV patients (2,3).     

Association study of a functional catechol-o-methyltransferase polymorphism and smoking in healthy Caucasian subjects

Tobacco smoking is a global health problem. The association of a functional common polymorphism in the catechol-o-methyltransferase gene (COMT Val158Met) with smoking behavior has been extensively studied, but with divergent findings. In the present study the frequency of COMT genotypes and alleles was evaluated in 578 male and a smaller group of 79 female unrelated, medication-free Caucasian healthy subjects of Croatian origin. Smokers were classified as subjects smoking ≤10 cigarettes per day, while subjects who never smoked in their life were regarded as nonsmokers. A χ²-test with standardized residuals and Bonferroni correction revealed significant (P = 0.017) differences in Met/Met, Met/Val or Val/Val genotype frequency between male smokers and nonsmokers. This significant association between COMT Val158Met polymorphism and smoking was not detected in female subjects, due to the small number of women, which represents a limitation of the study. Our results confirmed the significant association between COMT variants and smoking, which was due to the higher frequency of Val/Val homozygotes in male smokers compared to male nonsmokers. These results suggest that carriers of the high activity COMT variant are more prone to develop a higher level of nicotine dependence, or that they release more dopamine than carriers of Met/Met or Met/Val genotypes.     

The association of the decline in glomerular filtration rate with aggressive endometrial cancers

International Urology and Nephrology - Most site-specific cancer incidence is increased with the decrease of glomerular filtration rate (GFR). We analyzed endometrial cancers depending on different...     

PCR-based Y chromosome marker for discriminating between golden jackal (Canis aureus) and domestic dog (Canis lupus familiaris) paternal ancestry

Numerous reports of hybridization between wild Canis species and domestic dog suggest that hybridization between golden jackal and dog is likely. Here we present an assay of a Y chromosome marker for discriminating between golden jackal (Canis aureus) and dog (Canis lupus familiaris) paternal ancestry. Taking advantage of an insertion found in a dog Zfy intron haplotype but not in a golden jackal haplotype, we developed a three-primer PCR system in which species are differentiated based on the number of amplicons. Two amplicons are produced from domestic dog DNA template, while one amplicon is produced from golden jackal DNA template. Both amplicons can be analyzed in a single agarose gel electrophoresis run, while the longer amplicon also serves as an internal control. The method was validated using 27 golden jackal and 25 dog samples; all samples showed the expected amplicons. This simple and cost-effective method should prove useful for determining the direction of golden jackal–dog hybridization.