Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo

The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo.     

Partial and total monosomal karyotypes in myelodysplastic syndromes: comparative prognostic relevance among 421 patients

Myelodysplastic syndromes (MDS) include a group of heterogeneous hematological disorders with a variable risk of leukemic evolution and short survival. Around 40-50% of patients show abnormal karyotypes that are mostly characterized by monosomies or deletions. Cytogenetic findings are an independent prognostic factor and the International prognostic scoring system (IPSS) differentiates three cytogenetic categories, despite the Intermediate one being heterogeneous. The aim of this study, including 421 Argentinean patients with primary MDS, is to characterize the cytogenetic profile, to test its prognostic value and to compare partial and monosomal karyotypes against other cytogenetic findings. An abnormal karyotype (median survival: 26 months) was observed in 176 patients. The presence of complex karyotypes, number of alterations, and the IPSS cytogenetic groups showed significant differences for predicting outcome. Behavior of patients with isolated deletions (median survival: 49 months) did not differ from those with normal karyotype (56 months, P = 0.654) or Good prognostic findings (43 months, P = 0.371). However, a worse prognosis was observed when another alteration was added (31 months, P = 0.043). Karyotypes with autosomal monosomies (median survival: 16 months) had a prognostic impact similar to other Poor cytogenetic findings (17 months, P = 0.626). In our population classified according to French-American-British (FAB) or World Health Organization (WHO), this new categorization of cytogenetic abnormalities, recognizing three different risk groups, showed an independent prognostic impact and a better discriminating power than the IPSS categories. It can be concluded that all isolate deletions (excluding 7q-) are good prognostic findings and all monosomies (excluding Y chromosome loss) are bad indicators.     

Evaluation of the effects of the flavonoid apigenin on apoptotic pathway gene expression on the colon cancer cell line (HT29)

Apigenin (4',5,7-trihydroxyflavone) is one of the leading components supporting targeted treatment options. We explored the cytotoxic and apoptotic effects of various doses of apigenin administered alone and together with 5-fluorouracil (5-FU)-a chemotherapeutic agent with high cytotoxicity-for different incubation periods, on morphologic, DNA, RNA (messenger RNA [mRNA]), and protein levels on the p53 mutant HT29 human colon adenocarcinoma cell line. Treatment with apigenin alone for a 72-hour incubation at 90-μM dose resulted in an apoptotic percentage of 24.92% (P=.001). A higher percentage (29.13%) was observed after treatment with the same dose of apigenin plus 5-FU for the same incubation period (P=.001). These results were confirmed as mRNA and protein expression levels of caspase-3 increased 2.567-fold and mRNA expression levels of caspase-8 increased 3.689-fold compared with the control group. On the other hand, mRNA expression levels of mammalian target of rapamycin (mTOR) and cyclin D1 (CCND1) decreased by 0.423-fold and 0.231-fold, respectively. To our knowledge this is the first study showing that treatment with apigenin alone results in cell cycle arrest through activation of caspase cascade and stimulation of apoptosis in HT29 cells. It also shows that use of apigenin plus 5-FU further increases this effect. This study draws attention to the probable clinical effectiveness of apigenin plus a chemotherapeutic agent with high cytotoxicity. It also highlights the induction of desirable apoptotic effects by targeting the caspase cascade pathway through administration of reduced doses for shorter incubation periods.     

Implementation of a respiratory rehabilitation protocol: weaning from the ventilator and tracheostomy in difficult-to-wean patients with spinal cord injury

Purpose: Following repeated weaning failures in acute care services, spinal cord injury (SCI) patients who require prolonged mechanical ventilation and tracheostomy are discharged to their homes or skilled nursing facilities, with a portable mechanical ventilator (MV) and/or tracheostomy tube (TT) with excess risk of complications, high cost and low quality of life. We hypothesized that many difficult-to-wean patients with cervical SCI can be successfully managed in a rehabilitation clinic. The aim of our study was to develop a respiratory rehabilitation, MV weaning and TT decannulation protocol and to evaluate the effectiveness of this protocol in tetraplegic patients.

Methods: A multidisciplinary and multifaceted protocol, including respiratory assessment and management themes, was developed and performed based on the findings from other studies in the literature. Tetraplegic patients with the diagnosis of difficult-to-wean, who were admitted to the rehabilitation clinic after having been discharged from the intensive care unit to their home with home-type MV and/or TT, were included in this prospective observational study.

Results: The respiratory rehabilitation protocol was applied to 35 tetraplegic patients (10 home-type MV and tracheostomy-dependent, and 25 tracheostomized patients) with C1-C7 ASIA impairment scale grade A, B, and C injuries. Seven out of 10 patients successfully weaned from MV and 30 of 35 patients were decannulated. Four patients were referred for diaphragm pace stimulation and tracheal stenosis surgery. The mean durations of MV weaning and decannulation were 37 and 31 days, respectively.

Conclusions: A multifaceted, multidisciplinary respiratory management program can change the process of care used for difficult-to-wean patients with SCI.

• Implications for rehabilitation

• Findings from this study indicate the significance of a multidimensional evaluation of any reversible factors for prolonged MV- and/or TT-dependent SCI patients. Thus, rehabilitation specialists should take this into consideration and should provide the appropriate amount of time to these patients.

• The proposed protocol of respiratory rehabilitation for MV- and/or TT-dependent SCI patients shows promising results in terms of changing the care used for these patients.

• Successful implementation of a respiratory rehabilitation and weaning protocol is dependent on careful planning and detailed communication between the rehabilitation specialist and intensivist during the respiratory rehabilitation process.

• Because many of the so-called difficult- or impossible-to-wean patients were successfully weaned from MV and TT in the PMR clinic, the need for such an outlet for countries without specialized centers is supported.

     

Evaluation of genotoxic effects of 3-methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione on human peripheral lymphocytes

Context: Tranexamic acid is commonly used for curing abnormal bleeding in a variety of diseases. In a previous study, 12 different tetrahydro-2H-1,3,5-thiadiazine derivatives were synthesized from the amine group of tranexamic acid. Their antifibrinolytic and antimicrobial activities were compared with tranexamic acid. 3-Methyl-5-(4-carboxycyclohexylmethyl)-tetrahydro-2H-1,3,5-thiadiazine-2-thione (3-MTTT) was the most remarkable one, which may be used as a drug.

Objectives: In vitro genotoxicity of 3-MTTT was investigated using chromosome aberrations (CAs), sister chromatid exchanges (SCEs), micronucleus (MN) and comet assays.

Materials and methods: Various concentrations 0.78, 1.56, 3.13, 6.25, 12.50 and 25.00?μg/mL of 3-MTTT were applied to lymphocytes obtained from two donors for periods of 24 and 48?h. A negative (distilled water), a solvent (2:1 PBS:10% NaOH for cultured lymphocyte, and PBS for isolated lymphocytes) and a positive control (MMC for cultured lymphocytes and H₂O₂ for isolated lymphocytes) were also maintained.

Results: While this compound did not increase the frequency of abnormal cells and CA/cell ratio compared to negative control (except 48?h, 25?μg/mL), it significantly increased the frequency of SCEs at the four highest concentrations at both treatment periods (except 6.25?μg/mL, 48?h). It significantly decreased the MI in all the concentrations at 24?h (except 0.78?μg/mL) and in the highest three concentrations at 48?h. This compound did not significantly increase the frequency of MN and DNA damage compared to negative control. This compound did not affect the replication and nuclear division index.

Discussion and conclusion: Our results demonstrated that this compound does not represent a significant risk at the genetic level in in vitro human lymphocytes.     

Effects of interferon-gamma on bone remodeling during experimental tooth movement

OBJECTIVE: To determine the effects of interferon-gamma (IFN-gamma) on bone remodeling during orthodontic tooth movement. MATERIALS AND METHODS: Thirty adult male Sprague Dawley rats were randomly categorized into five groups. IFN-gamma was administered in three different doses (0.01, 0.02, and 0.05 microg/20 microL) and the remaining two groups served as control. Mandibular first molars were moved mesially by means of Ni-Ti closed coil springs in all groups. The results were evaluated histomorphometrically, and parameters of trabecular bone volume (BV/TV), trabecular bone number (Tr.N), and trabecular separation (Tr.Sep) were observed at the interradicular bone area of the mandibular first molars. RESULTS: Increases in BV/TV and Tr.N and decreases in Tr.Sep revealed the antiosteoclastic activity of IFN-gamma. CONCLUSION: IFN-gamma administration may be useful clinically for anchorage control.