Effect of the farnesyl transferase inhibitor L-744,832 on the colon cancer cell line DLD-1 and its combined use with radiation and 5-FU

BACKGROUND: Ras oncogenes are found in 25% of human tumors and they significantly affect prognosis. One of the major fields studied to improve anticancer drugs is blockade of the oncogenic ras protein function. One of the mechanisms to block the function of these proteins is to block farnesylation using a farnesyl transferase inhibitor (FTI) and thus to prevent the ras from anchoring to the cell membrane. METHODS: In this study, we investigated the effects of FTI L-744,832 either alone or in combination with 5-fluorouracil (5-FU; 1 microM/l) and radiotherapy (2, 6, and 10 Gy) on the colon cancer cell line DLD-1 with mutations in K-, N- and H-ras, c-myb, c-myc, p53, fos, sis and DNA repair genes. Drugs were added 3 h after cultivation. Radiotherapy was performed on the 3rd day of the study. On the 3rd day, medium and drugs were changed. Evaluations were performed on the 6th day. RESULTS: Administration of L-744,832, neither alone nor its combination with 5-FU and radiation, affected the number of DLD-1 cells and apoptosis rates. Regarding its effects on the cell cycle, L-744,832 was shown to lead to G(0)/G(1) and G(2)/M accumulation in a dose-dependent manner when administered alone. However, in combination with 5-FU, only a G(0)/G(1) accumulation was observed. CONCLUSION: Our study showed that FTI L-744,832 does not effect the cell number and apoptosis rate of DLD-1 cells and it cannot overcome 5-FU and radiation resistance, although it is able to modify some phases of the cell cycle.     

Endocarditis caused by Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is frequently isolated from hospital environments. In recent years, it has been reported that this bacterium is causing hospital infections at increasing rates and is gaining importance because of its multiple resistance. Although it has been related to several infections, endocarditis caused by S. maltophilia is rarely encountered. In this case study, endocarditis in a 40-y-old man with a history of aortic valve replacement is presented. Blood cultures revealed S. maltophilia to be the aetiological agent, which showed multiresistance to various antibiotics. Ticarcillin-clavulanate and trimethoprim-sulfamethoxazole were used in the treatment.     

Paradox in the cubital tunnel syndrome—frequent involvement of left elbow: first report

Objective

Cubital tunnel syndrome (CuTS) is the second most common compression neuropathy in the arm, but the existence of a compressive cause has not been determined conclusively and the majority of the cases are idiopathic. In this paper, involvement sides of limbs of patients with cubital tunnel syndrome were studied.

Material and methods

Between October 2008 and December 2011, the clinical assessment of consecutive operated patients with cubital tunnel syndrome in Rize Education and Research Hospital were analysed. The diagnosis and severity of syndrome was based on electro-diagnostic study.

Results

This study included 57 consecutive patients with cubital tunnel syndrome (39 men, 18 women; mean age, 44,7 years; range, 23–79 years; mean age, 44,7 years; range, 23–79 years); 31 patients underwent surgical treatment. Involvement was on the right side in 18 and on the left in 39 patients. Severity scores and MCV were statistically significant between sides.

Conclusion

Profound involvement with cubital tunnel was found in left elbow. According to the finding of non-dominant elbow involvement in our study, the exact etiology and ideal management of cubital tunnel syndrome continues to be heavily debated.     

Intracranial hemorrhage in infants as a serious,and preventable consequence of late form of vitamin K deficiency: a selfie picture of Turkey,strategies for tomorrow

Purpose

Vitamin K deficiency bleeding is one of the most common causes of acquired hemostatic disorder in early infancy. Although vitamin K is practiced routinely after every birth in Turkey, children with type of vitamin K deficiency bleedings (L-VKDB) can be encountered. We aimed to evaluate the clinical features of the children with L-VKDB reported from Turkey.

Methods

Between 1995 and 2013, 48 studies reporting 534 children with L-VKDB were evaluated in this study.

Results

Of the 534 reported children (178 girls, 356 boys), 486 (91 %) were extremely breastfed. The most common bleeding sites were intracranial hemorrhage, gastrointestinal, and umbilical in 414 (77.4 %), 33 (6.2 %), and 33 (6.2 %) children, respectively, and 35 (6.6 %) children had been diagnosed incidentally without any bleeding. The etiology of 399 (74.7 %) children were classified as idiopathic, whereas 135 (25.3 %) were secondary. Intramuscular vitamin K was administered in 248 (46.4 %), not administered in 228 (42.7 %), and the administration of vitamin K were not determined in 58 (10.9 %) children. The outcomes of Turkish cohort showed that 111 (20.8) children died, 257 (48.1 %) cases developed neurologic deficit (mainly epilepsy and psychomotor retardation), and only 166 (31.1 %) patients recovered without squeal.

Conclusions

The compliance of prophylactic measures in Turkey does not seem to be satisfactory. As a further measure of tomorrow, we vigorously emphasize that a national surveillance program may be initiated. An additional intramuscular dose or oral supplementation of vitamin K especially for exclusively breast-fed infants may reduce this catastrophic problem in our country.     

Congenital megalourethra presenting with large cystic mass in the inguinal area

Congenital megalourethra is a rare urogenital malformation characterized by severe dilatation and elongation of the penile urethra. It causes functional obstruction of the lower urinary system. Herein, we present a newborn with congenital megalourethra with single umbilical artery.     

Beneficial effects of Etanercept on experimental necrotizing enterocolitis

Purpose

Tissue damage in necrotizing enterocolitis (NEC) of infants occurs as a result of an uncontrolled inflammatory response. The aim of this study was to investigate any potential anti-inflammatory effects that Etanercept may have on the inflammatory response in an experimental NEC model in newborn rats.

Methods

Newborn pups were randomized into three groups immediately after birth (Control, NEC + Placebo and NEC + Etanercept). Pups in the NEC + Placebo and NEC + Etanercept groups were subjected to an NEC-inducing protocol (hypercarbia, hypothermia and hyperoxia) twice a day for 3 days. Pups in the NEC + Etanercept group were given an intraperitoneal injection of Etanercept. Rats were harvested for biochemical and histopathological examinations.

Results

The histopathological injury score of rats in the NEC + Placebo group was significantly higher compared to the NEC + Etanercept and Control groups (p < 0.05 for both comparisons). Tissue levels of tumor necrosis factor-α, interleukin-1β, and malondialdehyde were higher in the placebo group compared to the Etanercept group.

Conclusion

Our results suggest that Etanercept attenuates intestinal tissue damage in NEC by reducing inflammation and blocking the production of free-oxygen radicals, while also reducing tissue levels of tumor necrosis factor-α and interleukin-1β.