Frequency of common CYP3A5 gene variants in healthy Polish newborn infants

Cytochrome P450 monooxygenases catalyze the metabolism of approximately 40-60 % of widely used drugs with a A6986G CYP3A5 polymorphism determining expresser (A6986, *1) and reduced- expresser (*3) variants with modified drug metabolism activity. In this report, the allele frequency of CYP3A5 *1 and *3 (A6986 or G6986, respectively) was analyzed by the PCR-RFLP technique in a cohort of 200 Polish newborns from the West Pomeranian region. Of the studied group, 1 % (n = 2/200) proved homozygous for the CYP3A5*1 allele, 89 % (n = 178/200) for the *3 allele, and 10 % (n = 20/200) were heterozygous for *1/*3. Similar frequencies were found in other Caucasian European populations. This study provides basic genetic data related to the metabolism of drugs, with a narrow therapeutic window in a Polish population. Key words: CYP3A5 variants, pharmacogenetics, drug metabolis

tissue of rat adjuvant-induced arthritis

Triptolide has been clinically used to treat patients with rheumatoid arthritis, in which chemokine receptors play an important role in immune and inflammatory responses. To investigate the effect of triptolide on CCR5, we used complete Freund’s adjuvant to produce adjuvant-induced arthritis (AIA) in rats. Our data show that both CCR5 mRNA and protein levels in synovial tissue of rats with AIA are significantly higher than those in normal rats. Triptolide can significantly inhibit rat AIA-induced overexpression of CCR5 at both mRNA and protein levels. These results may contribute to better understanding of the therapeutic effects of triptolide in rheumatoid arthritis. Key words: triptolide, CCR5, adjuvant induced arthritis, rheumatoid arthriti

No effect of cancer-associated SNP rs6983267 in the 8q24 region on co-expression of MYC and TCF7L2 in normal colon tissue

A single nucleotide polymorphism (SNP) rs6983267, located within the 8q24 region, is strongly associated with risk of colorectal and prostate cancer. It has been suggested that the mechanism of this association is related to differential interaction of TCF7L2 protein (previously known as TCF-4) with alleles of rs6983267, influencing the expression of a well-known oncogene, MYC, located 335 Kb telomeric. Here, we tested the correlation between mRNA expression of MYC and several alternatively spliced forms of TCF7L2 in 117 non-cancer colon samples. We observed a strong correlation (r = 0.60, p < 10-6) between expression of MYC and a unique splicing form of TCF7L2. The level of MYC expression in these samples was associated with expression of some TCF7L2 splicing forms but not with genotypes of rs6983267, or interaction of rs6983267 with TCF7L2 expression. These findings suggest that some splicing forms of TCF7L2 may be functionally important for regulation of MYC expression in colon tissue but this regulation is not directly dependent on rs6983267

Less invasive treatment option for renal carcinoma with venous tumor thrombus

Aim To retrospectively analyze patients treated by renal tumor and venous tumor thrombus (VTT) removal and to introduce a less stressful and safer surgical method without thoracotomy in Neves level 3 cases. Methods From 2002 to 2011, 33 patients underwent surgery for renal cell cancer combined with tumor thrombus of the inferior vena cava. Preoperative symptoms, tumornode-metastasis classification of tumors, thrombus extension classified by Neves and Zincke system, types of surgical interventions, complications, postoperative management, and survival results were analyzed. Results Ten patients had level 1, 17 had level 2, and 6 had level 3 thrombi according to Neves and Zincke. In 5 patients with level 3 thrombi, the liver was mobilized without thoracotomy and in 1 patient endoluminal occlusion was utilized. There was no intraoperative mortality. The median survival time of 10 patients who died during follow-up period was 36.6 months (range, 0-121 months). Conclusion Renal cell cancer complicated with tumor thrombus without metastasis can be curable by performing a complete resection. The thrombus level determines the surgical approach and method. Our results confirm that level 3 caval vein tumor thrombus can be safely surgically treated by laparotomy with liver mobilization. Thoracotomy, use of cardiopulmonary bypass, and hypothermic circulatory arrest can be avoided with adequate liver-and vascular surgery methods. In 4%-15% of renal cell cancer cases, tumor thrombus is formed in the renal vein (RV) and later in the inferior vena cava (IVC), and in 1% the thrombus spreads into the right atrium (1-5). For advanced stage renal cell cancer a radical nephrectomy with removal of the tumor thrombus is required Zoltán MAteRIAL ANd MetHodS Patient population Between 2002 and 2011, at the Department of Urology, Semmelweis University 968 surgeries of renal cell cancer were performed. We studied the 33 cases in which renal cell cancer was combined with tumor thrombus of the RV and the ICV. Among them, there were 12 women (36.4%) and 21 men (63.6%), with the average age of 60.5 years (31-79 years, standard deviation 9.138). Preopeartive diagnostics Before each surgery, abdominal ultrasound and CT scan were performed, and in 21 cases MRI was performed (9-11). In level 2 cases, surgical procedure included the transperitoneal surgery through Chevron (subcostal)-incision: exploration, ligation of the renal artery, exclusion of the section above the IVC thrombus and the section below the renal veins followed by the exclusion of the intact renal vein, longitudinal cavotomy or the excision of the orifice of renal vein on the affected side, thrombectomy, flushing of the caval vein, de-gassing, lateral clamping of the cavotomy with Satinsky forceps, release of the exclusion, cavotomy closure with running suture, and nephrectomy. In level 1 cases, the cava was not involved, therefore the surgical intervention was less complicated, however in the level 3 cases the mobilization of the liver was required (11-13). The histological rating of the tumor was carried out according to the classification of Heidelberg, the staging was performed based on the 2010 tumor-node-metastasis (TNM) classification, and the histological grade was characterized according to Fuhrman (14, ReSuLtS Among 33 patients, there were 10 patients with level 1, 17 with level 2, and 6 with level 3. In these patients, Neves classification, number of cases, surgery type, and surgical time, the blood loss during surgery, intraoperative complications, reoperation and perioperative death was analyzed We surgically treated 6 patients with level 3 VTT. In 4 cases, the clamping was made bellow the hepatic veins. In these cases, there was no bleeding from the liver to the cavotomy. In 1 case, the tumor thrombus reached a higher position than in previous 4 cases, therefore the clamping was performed above the liver and the retrograde bleeding was reduced with the Pringle-maneuver. In 1 case, thrombectomy was performed using a Foley-catheter to overcome the endoluminal occlusion. The catheter easily passed by the solid tumor thrombus, there was no embolization, and the operative time was shorter than in other cases. The cavotomy, as well as the excision of the orifice of the affected renal vein, was closed with running suture using a Satinsky forceps for lateral clamping. There was no postoperative cava occlusion. Lymph node block dissection was performed in only 5 cases, in case of palpable enlarged lymph nodes. The infiltration of the caval vein wall was not observed in any of the cases, therefore cava resection was not needed. The average operative time was 3 hours and 34 minutes (2 hours-5 hours and 45 minutes). The median intraoperative blood loss was 1075 mL (200-3500 mL), which was substituted with 3.4 U (0-12 U) of red blood cell mass transfusion. Three reoperations were performed, one due to an injury of the contralateral ureter, one because of the bleeding from the removed kidney&apos;s bed, and one because of splenic injury. At the beginning of the less invasive surgical procedure, in 2 cases the clamping of vena cava was not performed, leading to pulmonary embolism. One occurred in the course of operation and the other at the time of the extubation. These patients received anticoagulant therapy and fully recovered. A patient, who suffered from multiple vascular disease, died on the second postoperative day. The cause of death was necrosis of the small bowel induced by the occlusion of the superior mesenteric artery. Other postoperative complications were not detected At the time of the operation, 11 patients (33.3%) had distant metastases, mostly in the lungs and the retroperitoneum. Other sites included the liver and the mediastinum. The maximum diameter of the renal tumor was on average 101 mm (50-280 mm). According to the TNM classification, 31 tumors were T3 and 2 cases were T4. Based on the Fuhrman staging there was 1 G1, 11 G2, 13 G3, and 8 G4-tumors. The median tumor thrombus length was 54 mm (10-130 mm). There was no intraoperative mortality. One patient died postoperatively (3%). The patients were monitored every 6 months after surgery. Serum creatinine, urea, and electrolyte levels were determined and abdominal ultrasound, chest, and abdominal CT examinations carried out. Survival time was determined in accordance with the date of death or the last follow-up date. The median follow-up period was 30 months (0-121 months). For RCC, the patients were treated with subcutaneous Interferon-1α 9 million units 3 times a week combined with 0.1 mg/kg body weight of intravenous vinblastine once a month. The duration of this therapy was determined by the general condition of the patients and the outcome of the disease -ideally it lasted for 1 year. In one case, due to the poor general condition of the patient, the postoperative oncologic treatment was disregarded. After 2008, 5 patients with distant metastases were treated with tyrosine kinase inhibitors. Seven of the 11 patients with distant metastases (33.3%) undergoing surgery died in an average of 12.1 months (3-19 months). Of the patients with no metastases at the time of surgery, 3 died, with median survival of 26.7 months (22-31 months). All deaths were caused by the postoperative progression of the underlying disease. Twenty-two patients (66.6%) were alive at the end of the follow-up. Four of them developed metastases following the surgery in an average time of 14.5 months (9-24 months). Eighteen patients without metastases had median survival time of 41.5 months (1-116 months) following surgery. The median survival rate for 33 patients calculated by the Kaplan-Meier survival was 18 months (range, 0-121) dIScuSSIoN The less invasive surgical approach used in this study reduced the complication rate, surgical time, and blood loss. In 5 cases, we preoperatively embolized the renal artery to reduce the tumor and the VTT size and to collapse the collateral veins (16-19). We did not notice complications like systemic reaction, embolization of another organ, and embolization of the tumor by disintegrating VTT published by other surgical teams (20,21). The surgical plan depends on the VTT level. Previously, the tumor thrombus levels 3 and 4 were treated using right thoracolaparotomy. Nowadays thoracolaparotomy is less frequent and the combination of median sternotomy and laparotomy is increasingly used instead. The Chevron-incision provides opportunity for liver mobilization, therefore the VC clamping can be done without thoracotomy. While initially the Chevron-incision was used only for the thrombi localized below the diaphragm, now it is also used for those localized above the diaphragm. As a result, moderate forms of tumor thrombus level 4 can be treated by laparotomy (12,13). The introduction of cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA) has allowed performing the dissection in a virtually blood-free area Our results show that level 3 caval vein tumor thrombus can be removed by a less aggressive surgical approach, underlining the benefits of a surgical intervention without thoracotomy. Acknowledgments We thank Dr Sandor G. Vari, MD, Director of the International Research and Innovation Management Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA and President of the RECOOP HST Association for critical review and helpful comments

Relational quality and media use in interpersonal relationships

Author final draft doi:10.1177/1461444807080339This study examined the relationship between relational quality and media use in interpersonal relationships. In addition, the impacts of other potentially important variables such as sex and relationship type of participants and their partners were explored. College student participants focused on interaction experiences with an acquaintance, friend, romantic partner, or family member. Questions addressed the sex of relational partners, how much of participants’ total communication with relational partners is conducted in each of three media (i.e., face-to-face, phone, and internet), and the quality of relationships. Results indicated that participant sex and partner sex did not affect reported media use, whereas relationship type had significant effects on the extent to which face-to-face and telephone communication were used. Specifically, among the college students studied, face-to-face communication was used least with family members and the telephone was used most with family members. Relationships with acquaintances had the lowest relational quality and romantic relationships, while closer, were less satisfying than either family or friendship relationships. Same-sex relationships were perceived as more satisfying than cross-sex relationships. Finally, media use did not predict relational closeness or satisfaction. Results are discussed in light of previous research on mediated interpersonal communication and conceptualizations of the role of communication technology in one’s social life are highlighted

Montenegro

The surface energy of disperse cadmium electrodeposits formation

J.Serb.Chem.Soc. 67(12)819–824(2002) UDC 616.37–008.61:612.349.8:611.018.5 JSCS–3006

red cell membrane protein

JSCS–3797

Mn2+, Co2+ and Ni2+ into nitrobenzene using strontium dicarbollylcobaltate and tetra-tert-butyl p-tert-butylcalix[4]arene tetraacetat