Anti-cancer effect of metformin on the metastasis and invasion of primary breast cancer cells through mediating NF-kB activity

Current evidence strongly suggests that aberrant activation of the nuclear factor kappa B (NF-kB) signaling cascade is connected to carcinogenesis. The matrix metalloproteinases (MMP) which are also the key agents for tumor metastasis may be potent candidates for tumor diagnosis in clinics. In this in vitro study, we hypothesized that metformin with an effective dose can inhibit tumor cell proliferation and metastasis by modulating the expressions of MMP-2 and -9 and interfering with NF-kB signaling in primary breast cancer cells (PBCCs). 300 000 cells per ml were obtained from biopsies of breast tumors from five human donors. The cell viability and proliferation were tested. Immunocytochemistry was performed for MMP-2, MMP-9, and NF-kB, and enzyme-linked immunosorbent assay for NF-kB activity, quantitative real-time PCR for RELA/p65, IkBα, MMP-2, and MMP-9. Three different doses of metformin (5, 10, and 25 mM) (Met) reduced the viability and proliferation of PBCCs in a dose-dependent manner, maximum inhibition was observed at 25 mM Met. The expression of RELA/p65 was not affected by 25 mM Met. Nuclear immunoreactivity and activity of NF-kB reduced while cytoplasmic NF-kB (p65) elevated by 25 mM Met compared to non-treatment (P < 0.05). The expression and immunoreactivity of MMP-9 but not MMP-2 were decreased by 25 mM Met treatment, compared with the non-treatment (P < 0.05). Metformin may have an essential antitumor role in the invasion and metastasis pathways of PBCCs by downregulating the MMP-9 expression blocking both the activity and nuclear translocation of NF-kB.     

The burden attributable to headache disorders in children and adolescents in Lithuania: estimates from a national schools-based study

BackgroundWe recently showed headache to be common in children (aged 7–11 years) and adolescents (aged 12–17) in Lithuania. Here we provide evidence from the same study of the headache-attributable burden.MethodsFollowing the generic protocol for Lifting The Burden’s global schools-based study, this cross-sectional survey administered self-completed structured questionnaires to pupils within classes in 24 nationally representative schools selected from seven regions of the country. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH; defined as mild headache with usual duration < 1 h). Burden enquiry was conducted in multiple domains.ResultsQuestionnaires were completed by 2505 pupils (1382 children, 1123 adolescents; participating proportion 67.4%), of whom 1858 reported headache in the preceding year, with mean frequency (±SD) of 3.7 ± 4.5 days/4 weeks and mean duration of 1.6 ± 1.9 h. Mean proportion of time in ictal state, estimated from these, was 0.9% (migraine 1.5%, probable medication-overuse headache [pMOH] 10.9%). Mean intensity on a scale of 1–3 was 1.6 ± 0.6 (mild-to-moderate). Symptomatic medication was consumed on 1.5 ± 2.8 days/4 weeks. Lost school time was 0.5 ± 1.5 days/4 weeks (migraine 0.7 ± 1.5, pMOH 5.0 ± 7.8) based on recall, but about 50% higher for migraine according to actual absences recorded in association with reported headache on the preceding day. More days were reported with limited activity (overall 1.2 ± 2.4, migraine 1.5 ± 2.2, pMOH 8.4 ± 8.5) than lost from school. One in 30 parents (3.3%) missed work at least once in 4 weeks because of their son’s or daughter’s headache. Emotional impact and quality-of-life scores generally reflected other measures of burden, with pMOH causing greatest detriments, followed by migraine and tension-type headache, and UdH least. Burdens were greater in adolescents than children as UdH differentiated into adult headache types.ConclusionsHeadache in children and adolescents in Lithuania is mostly associated with modest symptom burden. However, the consequential burdens, in particular lost school days, are far from negligible for migraine (which is prevalent) and very heavy for pMOH (which, while uncommon in children, becomes four-fold more prevalent in adolescents). These findings are of importance to both health and educational policies in Lithuania.     

Rhesus macaque dendritic cells efficiently transmit primate lentiviruses independently of DC-SIGN

Here, we describe the isolation and characterization of the rhesus macaque homolog for human DC-SIGN, a dendritic cell-specific C-type lectin. mac-DC-SIGN is 92% identical to hu-DC-SIGN. mac-DC-SIGN preserves the virus transmission function of hu-DC-SIGN, capturing and efficiently transducing simian and human immunodeficiency virus to target CD4(+) T cells. Surprisingly, however, mac-DC-SIGN plays no discernable role in the ability of rhesus macaque dendritic cells to capture and transmit primate lentiviruses. Expression and neutralization analyses suggest that this process is DC-SIGN independent in macaque, although the participation of other lectin molecules cannot be ruled out. The ability of primate lentiviruses to effectively use human and rhesus dendritic cells in virus transmission without the cells becoming directly infected suggests that these viruses have taken advantage of a conserved dendritic cell mechanism in which DC-SIGN family molecules are significant contributors but not the only participants.     

The effect of neuromuscular electrical stimulation on functional status and quality of life after knee arthroplasty: a randomized controlled study

[Purpose] The aim of this study was to investigate the effect of the addition of NMES to the post-TKA rehabilitation protocol on the functional status and quality of life of the patients. [Subjects and Methods] Patients were randomized into an exercise (control) and electrical stimulation (NMES) group. A home exercise program was prescribed for the control group. For the neuromuscular stimulation group 30 minute electrical stimulation applied to the vastus medialis muscle 5 days a week for 4 to 6 weeks. VAS, the timed up and go test, WOMAC and SF-36 scores were evaluated preoperatively and postoperatively at the first month and the third month of the follow-up period. [Results] Both the NMES group had 30 patients each, with 2 and 1 male patients respectively. The comparisons of WOMAC results at month 1 revealed that pain, stiffness, and total scores of the NMES group was significantly better than those of control group at the first and third months. Significantly better physical function and SF-36 subscales, except mental health, were found for the NMES group at the first month of follow-up. [Conclusion] The inclusion of the neuromuscular electrical stimulation program after knee arthroplasty was more effective at providing rapid improvements in knee pain, walking distance and quality of life.Key words: Quadriceps muscle, Knee joint, Arthroplasty     

Anaphylactic reaction to drugs commonly used for gastrointestinal system diseases: 3 case reports and review of the literature.

Proton pump inhibitors and H2 receptor antagonists, which are commonly used to treat peptic ulcer and gastroesophageal reflux diseases, are associated with a low incidence of adverse reactions. We report 3 cases of anaphylactic reactions induced by lansoprazole or ranitidine diagnosed in a population of 8304 first-referral patients over a 13-year period. Cutaneous sensitivity to famotidine, ranitidine, omeprazole, pantoprazole, and lansoprazole was evaluated by skin prick tests with a concentration of 10 mg/mL (at 1:1000, 1:100, 1:10 and 1:1 dilutions), and if they were negative, intradermal skin tests were performed with the same dilutions of the extracts. Single-blind, placebo-controlled oral provocation tests were performed with lansoprazole, omeprazole, famotidine, and ranitidine in 2 cases. One case involved anaphylaxis during an oral provocation test with lansoprazole, and 2 cases were anaphylactic reactions to ranitidine. In both cases the skin test was positive for ranitidine and in 1 case an oral provocation test was also positive. The second patient refused that test. Cross reactivity to other H2 receptor antagonists was not demonstrated and a safe alternative drug was found for all 3 patients. Although incidences of anaphylactic reactions induced by proton pump inhibitors or H2 reactions are rare, they can be life threatening.     

A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients

In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy—based on creatinine level, proteinuria and disease activity—was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.     

Effects of polyols on the quality characteristics of sucrose-free milk chocolate produced in a ball mill

Sucrose-free milk chocolates containing different types of bulk (isomalt, xylitol and maltitol) and high intensity (Stevia) sweeteners were produced by using a ball mill. The main quality characteristics of the formulated chocolates were evaluated and compared with those of the conventional sample containing sucrose. The Casson model was the best fitting model for the rheological data. Casson viscosity and Casson yield stress were significantly affected by the type of bulking agent in chocolates formulated with xylitol (p < 0.05). However xylitol notably improved the overall acceptability according to the sensory analysis results. Chocolates containing the sucrose replacers demonstrated lower T_onset values and higher enthalpy than the control sample. Sucrose-free chocolates illustrated a higher degree of particle agglomeration. Bulk sweeteners meanwhile seem to have high potential for milk chocolate production with low calorie values by using the ball mill technique. Industrial applications: the production of sucrose-free chocolates with conventional methods requires a lot of time and energy. Recently, using alternative methods for chocolate production has been raising interest in many small industries. This study proposed a ball mill method for the preparation of sucrose-free milk chocolates with physiochemical properties almost ranging in the standard limit defined for chocolate. Although using the ball mill method presents a more cost-effective technique for chocolate production and provides shorter processing times for small chocolate industries, it seems to be less efficient in evaporating moisture than the conventional processing. Challenges are still ahead for upgrading this alternative technique to be efficient in evaporating more moisture during operation ending in a high quality product.

Sucrose-free milk chocolates containing different types of bulk (isomalt, xylitol and maltitol) and high intensity (Stevia) sweeteners were produced by using a ball mill.     

Corrosive Substance Ingestion in Children

Objectives

To evaluate children who ingested corrosive substances, in terms of demographic features, nature of ingested substances, clinical findings, management and complications.

Methods

A total of 1709 cases aged between 0 and 16 y who ingested corrosive substance were analyzed retrospectively by evaluating the medical records of the patients.

Results

The mean age of the cases was 35.23?±?30.65 mo and male:female ratio was 1.45. Forty one percent of corrosive substances causing intoxication contained NaOH. Thirty percent of the families consisted of 5 or more members. Fourteen percent of the mothers were illiterate. Stricture formation was observed in 29 (1.69 %) of the cases during follow-up. In 79.31 % of those cases alkaline substance ingestion was responsible for stricture development. It was found that stricture formation occurred more frequently among cases who were older than 5 y of age and this finding was statistically significant (p?=?0.001).

Conclusions

The cases older than 5 y of age with the diagnosis of grade 2b esophagitis must be followed up closely for the stricture formation. In order to protect children from corrosive ingestion, importance must be given to preventive measures such as education of families, keeping and storing these agents out of the reach of children and providing safety caps for these products.