The Effects of Chronomodulated Therapy with 5-Fluorouracil (5-Fu) and Folinic Acid (Fa) on the Toxicity and Quality of Life in Patients with Advanced Gastric Cancer

This study was designed to assess the tolerability of chronomodulated infusion chemotherapy, individualized by the rhythm of peripheral blood cells. Twenty patients with metastatic gastric cancer were randomized to chronotherapy or day-time arms of 5-fluorouracil (FU) (600 mg/m², 8 h inf.d1-5) and folinic acid (FA) (20 mg/m², iv, d1-5) in the first cycle and crossed-over to the other arm in the following cycles. Ten of 18 evaluable patients were assigned to chronotherapy arm and eight to day-time in the first cycle. Although there was no significant difference between two arms on enrollment, chronotherapy arm yielded an improvement of 45% of QLQ-C30 scores (p = 0.021) and the day-time arm had 11% improvement (p = 0.575). After the crossing-over, chronotherapy arm, again, had a significant improvement in QLQ-C30 scores, compared to the day-time arm (14% vs. -18%, p = 0.001, respectively). Mucositis/diarrhea was significantly higher in the day-time arm compared to chronotherapy arm (p = 0.015). In conclusion, chronomodulated infusion of 5-FU might improve the quality of life.     

Detection of p16 promotor hypermethylation in “Maras powder” and tobacco users

Background: A plant powder called “Maras powder” is widely used instead of cigarette smoking in the South-Eastern region of Turkey. It has been confirmed that this powder comprises tobacco Nicotiana rustica L. Methods: The aim of this study was to assess the effect of Maras powder and cigarette smoking on the P16 promotor hypermethylation. Twenty-two Maras powder users (Group I), 12 cigarette smokers (Group II), and 16 healthy controls who neither smoked nor used Maras powder (Group III) were included in the study. Hypermethylation of the P16 gene was examined using methylation-specific PCR (MSP) method in the blood of the three groups. Results: Aberrant P16 methylation was found in 7 of the 22 (31.8%) in Group I, in 3 of 12 (25%) in Group II, and in 1 of 16 (6.25%) in Group III. Conclusion: Maras powder may be as harmful as cigarette smoking, leading to hypermethylation in P16 and warrants detailed studies on this subject.     

Time course of hemorheological alterations after heavy anaerobic exercise in untrained human subjects.

The time course of hemorheological alterations was investigated after heavy anaerobic exercise in untrained male human subjects. The Wingate protocol was performed by each subject, and blood lactate, red blood cell (RBC) deformability and aggregation, white blood cell (WBC) activation, and several hematological parameters were investigated during 24 h after the exercise and compared with preexercise values. Compared with the preexercise value, blood lactate level was found to be approximately 10-fold higher immediately after the exercise. There was a transient, significant increment of RBC and WBC counts immediately after exercise that was followed by a decrement of RBC count. There was a second increase of WBC count, accompanied with increased percentages of granulocytes and granulocyte activation, starting 45 min after exercise. RBC deformability was found to be impaired immediately after exercise and remained reduced for at least 12 h; RBC aggregation was also found to be decreased after exercise, with the onset of this decrease delayed by 30 min. The results of this study indicate that a single bout of heavy anaerobic exercise may induce significant hemorheological deterioration lasting for up to 12 h and thus suggest the need to consider such effects in individuals with impaired cardiovascular function.     

Nesfatin-1 and ghrelin levels in serum and saliva of epileptic patients: hormonal changes can have a major effect on seizure disorders

Nesfatin-1 and ghrelin are the two recently discovered peptide hormones involved in the control of appetite. Besides its main appetite-control function, ghrelin also has anticonvulsant effects, while nesfatin-1 causes depolarization in the paraventricular nucleus (PVN). The aims of this study, therefore, were to investigate: (i) whether there are differences in the concentrations of nesfatin-1 and ghrelin in saliva and serum samples between eplilepsy patients and normal controls and (ii) whether salivary glands produce nesfatin-1. The study included a total of 73 subjects: 8 patients who were newly diagnosed with primary generalized seizures and had recently started antiepileptic drug therapy; 21 who had primary generalized seizures and were continuing with established antiepileptic drug therapy; 24 who had partial seizures (simple: n = 12 or complex: n = 12) and were continuing with established antiepileptic drug therapy; and 20 controls. Salivary gland tissue samples were analyzed for nesfatin-1 expression by immunochemistry and ELISA. Saliva and serum ghrelin levels were measured by ELISA and RIA, and nesfatin-1 levels by ELISA. Nesfatin-1 immunoreactivity was detected in the striated and interlobular parts of the salivary glands and the ducts. The nesfatin-1 level in the brain was around 12 times higher than in the salivary gland. Before antiepileptic treatment, both saliva and serum nesfatin-1 levels were around 160-fold higher in patients who are newly diagnosed with primary generalized epilepsy (PGE) than in controls; these levels decreased with treatment but remained about 10 times higher than the control values. Saliva and serum nesfatin-1 levels from patients with PGE and partial epilepsies who were continuing antiepileptic drugs were also 10-fold higher than control values. Serum and saliva ghrelin levels were significantly (twofold) lower in epileptic patients before treatment than in controls; they recovered somewhat with treatment but remained below the control values. These results suggest that the low ghrelin and especially the dramatically elevated nesfatin-1 levels might contribute to the pathophyisology of epilepsy. Therefore, serum and saliva ghrelin and especially the remarkably increased nesfatin-1 might be candidate biomarkers for the diagnosis of epilepsy and for monitoring the response to anti-epileptic treatment.