Evaluation of leukocyte arylsulphatase a, serum interleukin-6 and urinary heparan sulphate following tamoxifen therapy in breast cancer.

Leukocyte arylsulphatase A (AS-A) was shown to be significantly high in newly-diagnosed breast cancer patients. Previous reports imply a connection between serum interleukin-6 (IL-6) and breast cancer, possibly through a modulation of enzymes involved in estrogen synthesis. Abnormal distribution of heparan sulphate proteoglycans (HSPGs) in malignant breast epithelial cells suggests that they play a key role in the regulation of cell growth. Estradiol is believed to be effective in modulating glycosaminoglycans (GAGs) and their depolymerizing enzymes. Therefore, in this study, attempts were made to evaluate the activity of leukocyte arylsulphatase A, serum interleukin-6, urinary GAGs and heparan sulphate (HS) in response to tamoxifen (TAM) therapy in mastectomised breast cancer patients. Thirty-four patients (aged 30-82 years) were administered TAM (20 mg twice daily). Blood and urine samples of each patient were collected three times (at the beginning, and in third and sixth month of TAM therapy), and biochemical parameters were measured. There was no difference between baseline leukocyte AS-A activity and that measured after three months. At the end of six months, enzyme activity was significantly higher than the former values (p=0.022), but within the reference intervals reported in the literature. Although this increase might imply a normalization, the duration of TAM therapy is not long enough to make a decision about either regression or aggravation of the disease. TAM did not have any effect on serum IL-6, urinary HS and GAG levels which may be due to insensitivity of these variables to TAM during the short period of therapy. Both urinary GAG and HS levels measured at sixth month exhibited a positive correlation with the baseline level of leukocyte AS-A (p=0.005 and 0.009, respectively), suggesting that positive responses to the drug might be seen in patients with low AS-A activity.     

Ceruloplasmin level in women with breast disease. Preliminary results.

The average ceruloplasmin levels of 29 patients with active breast cancer and 22 patients in remission were 824 +/- 61 mg/l and 630 +/- 18 mg/l respectively. The average ceruloplasmin level of 17 patients with benign breast diseases was 555 +/- 29 mg/l and of 18 healthy women in a control group 584 +/- 17 mg/l. Breast cancer patients not in remission had ceruloplasmin levels which were significantly increased when compared to the other 3 groups. The CA 15-3 levels and ceruloplasmin levels were positively correlated. We propose that ceruloplasmin may be used as a tumour marker in the follow-up of patients with breast cancer.     

Season of birth and fluctuating asymmetry.

Fluctuating asymmetry (FA) refers to random, small deviations from perfect bilateral symmetry in morphological traits. These minor deviations from the ideal phenotype reflect environmental and genetic perturbations experienced during ontogeny. FA has been associated with negative health outcomes and many developmental disorders in humans. The prevalence of developmental disorders and adult health vary according to the month of birth, suggesting that seasonal stressors may leave enduring signs in the adult body, marked by high FA. The current study examined the relationship between FA and birth season. Data were collected for 205 males and females (average age = 20.39 years) on FA of 10 bilateral traits (second, third, fourth, and fifth digit length, palm height, wrist diameter, elbow width, ear height, foot breadth, and ankle circumference). Additional relationships were also investigated among FA, testosterone (T), and birth order. Results indicate that ear FA was lower for fall births compared to winter births in males. In females, palm FA was lower for fall births compared to those of the spring. FA of the digits was positively associated with T in males. Average FA, excluding the digits, decreased as the number of maternal siblings increased for both sexes. T concentrations in males were positively associated with the number of younger brothers. Our results generally confirm previous research on seasonal variation in adult longevity and neurological and psychiatric disorders, suggesting that winter and spring births are at risk for asymmetric developmental trajectory.     

Sequence analysis of rpoB mutations in rifampin-resistant clinical Mycobacterium tuberculosis isolates from Turkey

Drug-resistant tuberculosis is a serious problem throughout the world. Resistance to Rifampicin (RIF) is mainly caused by the mutations in the rpoB gene coding the beta-subunit of RNA polymerase. In this study, we aimed to detect the distribution of rpoB gene mutations in 80 RIF-resistant clinical Mycobacterium tuberculosis (MTB) isolates from Turkey. The rpoB gene was amplified by PCR and mutations leading to RIF resistance were determined by automated sequence analysis. A total of 72 of the 80 isolates (90%) were found to carry mutations in the amplified region, whereas eight isolates (10%) carried no mutations. Overall, 24 different missense mutations affecting 14 codons, and two deletion mutants were identified. Nine new mutations, six in the hot-spot region and three outside this region, were found. The codon numbers of the most frequently encountered mutations were 531 (51.4%), 526 (18.1%), 516 (13.9%), and 513 (12.5%). As a result, 90% of the RIF-resistant MTB isolates from the Turkish patients were found to carry a mutation in the rpoB gene, Ser531Leu being the most frequent one. Although molecular methods identify mutations leading to RIF resistance very quickly, results of the antimycobacterial susceptibility tests must be taken into consideration for the patients carrying no mutations in this region.     

The role of cartilage canals in endochondral and perichondral bone formation: are there similarities between these two processes?

We investigated the development of cartilage canals to clarify their function in the process of bone formation. Cartilage canals are tubes containing vessels that are found in the hyaline cartilage prior to the formation of a secondary ossification centre (SOC). Their exact role is still controversial and it is unclear whether they contribute to endochondral bone formation when an SOC appears. We examined the cartilage canals of the chicken femur in different developmental stages (E20, D2, 5, 7, 8, 10 and 13). To obtain a detailed picture of the cellular and molecular events within and around the canals the femur was investigated by means of three-dimensional reconstruction, light microscopy, electron microscopy, histochemistry and immunohistochemistry [vascular endothelial growth factor (VEGF), type I and II collagen]. An SOC was visible for the first time on the last embryonic day (E20). Cartilage canals were an extension of the vascularized perichondrium and its mesenchymal stem cell layers into the hyaline cartilage. The canals formed a complex network within the epiphysis and some of them penetrated into the SOC were they ended blind. The growth of the canals into the SOC was promoted by VEGF. As the development progressed the SOC increased in size and adjacent canals were incorporated into it. The canals contained chondroclasts, which opened the lacunae of hypertrophic chondrocytes, and this was followed by invasion of mesenchymal cells into the empty lacunae and formation of an osteoid layer. In older stages this layer mineralized and increased in thickness by addition of further cells. Outside the SOC cartilage canals are surrounded by osteoid, which is formed by the process of perichondral bone formation. We conclude that cartilage canals contribute to both perichondral and endochondral bone formation and that osteoblasts have the same origin in both processes.     

Long-term use and tolerability of cyclooxygenase-2 inhibitors in patients with analgesic intolerance.

BACKGROUND: Cyclooxygenase-2 (COX-2) inhibitors are reported to be well tolerated in patients with analgesic intolerance (AI). However, limited data are available about the long-term tolerability of these drugs. OBJECTIVE: To determine the long-term tolerability of COX-2 inhibitors in patients with Al. METHODS: Patients with AI who previously underwent single-masked, placebo-controlled oral provocation tests and were found to tolerate nimesulide, meloxicam, rofecoxib, or celecoxib were interviewed regarding the long-term use and tolerability of these drugs. RESULTS: Of 87 patients, 61 (70%) had used the recommended COX-2 inhibitor(s). Of the 61 users, 54 (89%) tolerated the drug(s) well and 7 (11%) reported adverse events. Three patients reporting adverse events were rechallenged with the responsible COX-2 inhibitor, and their results were found to be negative. CONCLUSIONS: Long-term use of COX-2 inhibitors was tolerated well by most patients with AI, and placebo-controlled oral provocation tests, as a single test, seemed to predict tolerability. Furthermore, self-reported positive reactions in the long-term should also be confirmed with rechallenge tests for definite diagnosis.     

The prevalence of fecal colonization of enterococci, the resistance of the isolates to ampicillin, vancomycin, and high-level aminoglycosides, and the clonal relationship among isolates

The gastrointestinal tract carriage of enterococci was searched in 150 hospitalized patients and 100 outpatients, and clonal relatedness of the isolates and their resistance to ampicillin, vancomycin, and high-level streptomycin and gentamicin were investigated. A stool sample or rectal swab collected from each patient was inoculated into appropriate media within an hour. Enterococcus species were identified by using conventional biochemical tests, API-20 Strep assay, and BBL crystal kit. Antibiotic susceptibility tests were performed using Kirby-Bauer disk diffusion method. A polymerase chain reaction (PCR) was used to detect vanA and vanB genes. Pulsed-field gel electrophoresis (PFGE) and arbitrarily primed-polymerase chain reaction (AP-PCR) methods were used for molecular typing of the strains. Enterococci were isolated from 90 (60%) of the specimens collected from 150 inpatients. Of these 90 isolates, 37 (41%) had high-level gentamicin resistance, 36 (40%) had high-level streptomycin resistance, and 50 (55.6%) had ampicillin resistance. Fecal colonization was found in 30% of the outpatients. Resistances to ampicillin, high-level streptomycin, and gentamicin were 13%, 10%, and 3%, in these patients' isolates, respectively. No vancomycin-resistant enterococci were detected by both agar diffusion and PCR assays in our study. Both typing procedures were applied on 78 Enterococcus strains isolated from inpatients. AP-PCR typing showed that 30 (50.8%) of the 59 E. faecium and 5 (50%) of the 10 E. faecalis strains were clonally related. These values were found to be 12 (20.3%) and two (20%) by PFGE, respectively. The typing procedures did not find any clustered strains in the six E. durans and three E. avium isolates. Neither PFGE nor AP-PCR result was significantly different among the sensitive and resistant strains. Our results indicate that the high prevalence of colonization with ampicillin and highlevel aminoglycoside-resistant enterococci is an important problem in our medical center. The high clonal diversity among the isolates indicates limited spread of antibiotic-resistant strains between patients.     

Effects of Different Doses of Caffeinated Coffee on Muscular Endurance,Cognitive Performance,and Cardiac Autonomic Modulation in Caffeine Naive Female Athletes

Caffeine is widely consumed among elite athletes for its well-known ergogenic properties, and its ability to increase exercise performance. However, studies to date have predominantly focused on the anhydrous form of caffeine in male participants. The aim of the study was to investigate the effect of caffeinated coffee ingestion on lower-upper body muscular endurance, cognitive performance, and heart rate variability (HRV) in female athletes. A total of 17 participants (mean ± standard deviation (SD): age = 23 ± 2 years, body mass = 64 ± 4 kg, height = 168 ± 3 cm) in a randomized cross-over design completed three testing sessions, following the ingestion of 3 mg/kg/bm of caffeine (3COF), 6 mg/kg/bm of caffeine (6COF) provided from coffee or decaffeinated coffee (PLA) in 600 mL of hot water. The testing results included: (1) repetition number for muscular endurance performance; (2): reaction time and response accuracy for cognitive performance; (3): HRV parameters, such as standard deviation of normal-to-normal (NN) intervals (SDNN), standard deviation of successive differences (SDSD), root mean square of successive differences (RMSSD), total power (TP), the ratio of low- and high-frequency powers (LF/HF), high-frequency power (HF), normalized HF (HFnu), low-frequency power (LF), and normalized LF (LFnu). A one-way repeated measures ANOVA revealed that 3COF (p = 0.024) and 6COF (p = 0.036) improved lower body muscular endurance in the first set as well as cognitive performance (p = 0.025, p = 0.035 in the post-test, respectively) compared to PLA. However, no differences were detected between trials for upper body muscular endurance (p = 0.07). Lastly, all HRV parameters did not change between trials (p > 0.05). In conclusion, ingesting caffeinated coffee improved lower body muscular endurance and cognitive performance, while not adversely affecting cardiac autonomic function.     

Protective effects of dexmedetomidine on ischaemia-reperfusion injury in an experimental rat model of priapism

The study aimed to investigate the effects of dexmedetomidine against ischaemia-reperfusion injury occurring after priapism in a model of induced-priapism in rats. A total of 18 male rats were randomised into three groups. Group 1 was the control group. A priapism model was performed rats in Group 2 and then ischaemia-reperfusion injury was evaluated. Group 3 had similar procedures to the rats in Group 2. Rats in Group 3 additionally had 100 μg/kg dexmedetomidine administered intraperitoneally immediately after reperfusion. Blood and tissue samples were analysed. Biochemical analysis of blood samples revealed a decrease in the levels of the pro-inflammatory cytokines including interleukin-1 beta (IL-1 Beta), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha) in Group 3 compared to Group 2 (p:.04, p:.009 and p:.009, respectively). Similarly, the highest malondialdehyde (MDA) level was in Group 2 (p:.002). The levels of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were significantly higher in Group 3 than that of Group 2 (p:.037 and p:.045, respectively). Direct microscopic examinations revealed positive changes in desquamation, oedema, inflammation and vasocongestion scores in Group 3 compared to Group 2 (p:.007, p:.008, p:.007 and p:.006, respectively). Dexmedetomidine has a protective effect against ischaemia-reperfusion injury in penile tissue.