Evaluation of important human CYP450 isoforms and P-glycoprotein phenotype changes and genotype in type 2 diabetic patients,before and after intensifying treatment regimen using Geneva cocktail

The present study evaluates the influence of type 2 diabetes (T2D) on important CYP450 (CYP) isoforms and P-glycoprotein (Pgp) transporter activities before and 3 months after an intensifying treatment regimen involving 40 patients. Results have been compared with 21 non-T2D healthy participants (the control group). CYPs and Pgp activities were assessed after administering the Geneva cocktail. The mean metabolic ratios (MR) for CYP2B6 (1.81 ± 0.93 versus 2.68 ± 0.87), CYP2C19 (0.420 ± 0.360 versus 0.687 ± 0.558) and CYP3A4/5 (0.487 ± 0.226 versus 0.633 ± 0.254) significantly decreased in T2D patients compared to the control group (p < 0.05). CYP2C9 (0.089 ± 0.037 versus 0.069 ± 0.017) activities slightly increased in diabetic patients, and no difference was observed regarding CYP1A2 (0.154 ± 0.085 versus 0.136 ± 0.065), CYP2D6 (1.17 ± 0.56 versus 1.24 ± 0.83), and Pgp activities in comparison to the control group. Three months after the intensifying treatment regimen, MRs of CYP2C9 (0.080 ± 0.030) and CYP3A4/5 (0.592 ± 0.268) improved significantly and were not statistically different compared to the control group (P > 0.05). Several covariables, such as inflammatory markers (IL-1β and IL-6), genotypes, diabetes and demographic-related factors, were considered in the analyses. The results indicate that chronic inflammatory status associated with T2D modulates CYP450 activities in an isoform-specific manner.     

Femoral shaft fractures in childrenElastic stable intramedullary nailing in 31 cases

We report our experience with elastic stable intramedullary titanium nailing (ESIN) of femoral shaft fractures in children. From 1998 to 2001, we treated 31 children (20 boys), median age 6 (4–11) years, with ESIN for 29 closed and 2 grade I open femoral shaft fractures. We reviewed 30 children clinically after median 1.5 (1–3) years. Their median hospital stay was 6 (2–20) days. All fractures were radiographically united at a median of 7 (5–9) weeks. The nails were removed in 29 children after a median of 22 (6–38) weeks postoperatively. At follow-up, we found a leg-length discrepancy up to 1 cm in 6 children and 10 degrees of internal rotational deformity in 1 child. No angular deformity had occurred. Elastic stable intramedullary nailing seems to be a safe method for the treatment of femoral shaft fractures in children between 4 and 11 years of age.     

Epidemiology of bacterial hand infections.

OBJECTIVE: The aim of the study was to delineate and update the bacteriological spectrum, characterize patterns and sites of injury, evaluate laboratory tests and possible causes of complications in patients with bacterial hand infections. METHODS: All hand infections operated on in the department of orthopedics at Odense University Hospital during the period 1992-2001 were reviewed retrospectively. A standard protocol was used to collect data for each patient. We also examined all laboratory reports and recorded the identity of the etiologic organism, if known, for all cases of bacterial hand infections. RESULTS: Four hundred and eighteen patients (296 men and 122 women) with hand infections were operated on between 1992 and 2001 in our department. The median age of the patients was 40 years (range 1-93). The average interval from primary injury to operation was 10 days (range 1-50). The etiology was laceration/puncture in 35%. The site of infection was subcutaneous in 45% followed by tendon, joint and bone in 27, 18 and 5%, respectively. The bacteria isolated from the patients showed that 184 cultures (44%) were pure Staphylococcus aureus followed by 49 cultures (11.7%) of mixed organisms. Body temperature and C-reactive protein (CRP) were normal in three quarters of all patients with hand infections in our series. However the erythrocyte sedimentation rate (ESR) was elevated in 50% of the patients and was a significantly better test for infection in this study than CRP (p = 0.002). Neither the severity of infection nor the etiology of infection was related in any way to the initial temperature, CRP or ESR in this study. Complications were noted in 14.8% of all patients, and were especially related to diabetes, and mixed infection. CONCLUSION: Despite modern antibiotics, hand infections with a variety of organisms continue to be a source of morbidity and possible long-term disability. Most hand infections are the result of minor wounds that have been neglected. A complete history and physical examination is necessary to exclude other associated medical conditions (diabetes, arthritis, immunosuppression) that may compromise therapy. Furthermore, our study confirms that Staphylococcus aureus is responsible for most instances of hand infection, followed by mixed organisms. Gram-negative organisms are frequently cultured in patients with diabetes and intravenous drug abuse.     

The Inhibitory Effect of Epigallocatechin Gallate on the Viability of T Lymphoblastic Leukemia Cells is Associated with Increase of Caspase-3 Level and Fas Expression

Acute lymphoblastic leukemia is the most prevalent cancer in children. Novel components to help struggle aggressive malignancies and overcome some side effects of conventional treatments could be a promising strategy. Epigallocatechingallate (EGCG), have attracted the attention of scientists for prevention or treatment of some cancers. Jurkat cells were incubated with the different concentrations of EGCG (30–100 µm) for 24, 48, and 72 h and cell viability was investigated using MTS test. Apoptosis and the level of caspase 3 alterations were evaluated using flowcytometry and expression of Fas by Real Time PCR. EGCG decreased viability of cells with an inhibition concentration (IC50) of 82.8 ± 3.1, 68.8 ± 4 and 59.7 ± 4.8 μM in 24,48 and 72 h. 50, 70 and 100 µM concentrations of EGCG induced apoptosis in about 31, 40 and 71% of the cells, respectively. The mean value of caspase 3 positive cells in the presence of 50, 70 and 100 µm concentrations of EGCG was 19.3 ± 2.9, 29.5 ± 3.1 and 61.2 ± 3.4 respectively compared to 7.8 ± 1.1 in control with a significant difference at 100 µm concentration. Treatment with EGCG for 48 h enhanced the expression of Fas reaching to a significant level at 100 µM concentration. EGCG is effective in decrease cell viability, apoptosis induction and enhancement of caspase 3 and Fas expression level in jurkat cells. A comprehensive understanding of molecular events and pharmacokinetics of the component and experiments in animal models are required for dose determination and its interaction with other components of combination chemotherapy.     

Correction of Congenital Brachymetatarsia by Gradual Callus Distraction

Two children with congenital brachymetatarsia of the fourth metatarsal bone were treated by osteotomy of the metatarsal bone and bone lengthening by the Ilizarov technique. Both children were cosmetically improved.     

Correlation between antioxidant activity of garlic extracts and WEHI-164 fibrosarcoma tumor growth in BALB/c mice

The biological activities of garlic may be affected by different processing methods. This study, therefore, aimed to evaluate potential anticancer effects of different type of processed garlic extracts on WEHI-164 tumor cells in inbred BALB/c mice and correlate the tumor growth rates with some garlic constituents. In a preclinical trial 60 BALB/c mice were injected with WEHI-164 tumor cells and divided into six groups of 10 animals. Group 1 mice received 200 μL of saline, and groups 2-6 were injected intraperitoneally with fresh, microwaved, 3-month-old, leaves, and boiled garlic extracts, respectively, at 20 mg/kg/0.2 mL. Three weeks following tumor inoculation, the mean tumor size in garlic extract-treated groups was reduced with significant reductions observed in the fresh and microwaved extract groups compared with the control group (P<.05). The antioxidant capacity and the amounts of allicin, flavonoids, and phenolic compounds in differentially processed garlic were evaluated and correlated with their anticancer activities. There was a linear correlation between the amounts of allicin, flavonoids, or phenolic components derived from fresh, microwaved, 3-month-old, leaves, and boiled garlic and cancer growth prevention. In conclusion, garlic has anticancer activity against WEHI-164 tumor cells, and processing such as heating reduces its effect dramatically. The anticancer activities of different kinds of garlic are related to the level of allicin, flavonoids, and phenolic components. Therefore, fresh garlic has the highest content of bioactive components and the greatest anticancer efficacy.