Design,synthesis, and in vitro biological evaluation of novel thiazolopyrimidine derivatives as antileishmanial compounds

A series of thiazolopyrimidine derivatives was designed and synthesized as a Leishmania major pteridine reductase 1 (LmPTR1) enzyme inhibitor. Their LmPTR1 inhibitor activities were evaluated using the enzyme produced by Escherichia coli in a recombinant way. The antileishmanial activity of the selected compounds was tested in vitro against Leishmania sp. Additionally, the compounds were evaluated for cytotoxic activity against the murine macrophage cell line RAW 264.7. According to the results, four compounds displayed not only a potent in vitro antileishmanial activity against promastigote forms but also low cytotoxicity. Among them, compound L16 exhibited an antileishmanial activity for both the promastigote and amastigote forms of L. tropica, with IC₅₀ values of 7.5 and 2.69 µM, respectively. In addition, molecular docking studies and molecular dynamics simulations were also carried out in this study. In light of these findings, the compounds provide a new potential scaffold for antileishmanial drug discovery.     

New nanodrug design for cancer therapy: Its synthesis,formulation, in vitro and in silico evaluations

The aim of this study was to develop a novel nanosize drug candidate for cancer therapy. For this purpose, (S)-methyl 2-[(7-hydroxy-2-oxo-4-phenyl-2H-chromen-8-yl)methyleneamino]-3-(1H-indol-3-yl)propanoate (ND3) was synthesized by the condensation reaction of 8-formyl-7-hydroxy-4-phenylcoumarin with l -tryptophan methyl ester. Its controlled release formulation was prepared and characterized by different spectroscopic and imaging methods. The cytotoxic effects of ND3 and its controlled release formulation were evaluated against MCF-7 and A549 cancer cell lines, and it was found that both of them have a toxic effect on cancer cells. For drug design and process development, the molecular docking analysis technique helps to clarify the effects of some DNA-targeted anticancer drugs to determine the interaction mechanisms of these drugs on DNA in a shorter time and at a lower cost. By using the molecular docking analysis and DNA binding assays, the interaction between the synthesized compound and DNA was elucidated and non-binding interactions were also determined. To predict the pharmacokinetics, and thereby accelerate drug discovery, the absorption, distribution, metabolism, excretion and toxicity values of the synthesized compound were determined by in silico methods.     

Ultrasonographic evaluation of the femoral cartilage thickness in patients with chronic renal failure

Objective To investigate the effects of chronic renal failure (CRF) on the distal femoral cartilage thickness by using ultrasonography and to determine the relationship between cartilage thickness and certain disease-related parameters. Design Fifty-seven CRF patients (41 male and 16 female) (mean [SD] age, 44.7 [12.1] years) and 60 healthy controls (41 male and 19 female) (mean [SD] age, 43.5 [13.3] years) were enrolled in this study. Demographic and clinical characteristics were recorded. Cartilage thickness measurements were taken from the medial and lateral condyles, and intercondylar areas of both knees. Results Groups were similar in terms of age, weight, height, body mass index and gender (all p>0.05). The mean cartilage thickness was found to be less in CRF patients than in controls (statistically significant for medial condyles and intercondylar areas both in right and the left knees [all p<0.05]). Cartilage thickness showed no correlation with eGFR, and with the levels of serum urea, creatinine, calcium, magnesium, phosphor, hemoglobin, uric acid and as well as steroid use (all p>0.05) in CRF patients. Conclusion In the light of our findings, we imply that patients with CRF have thinner femoral cartilage than healthy controls. This result may support the view that patients with CRF are at increased risk for developing early knee osteoarthritis. Last but not least, clinicians should be aware of the importance of rehabilitation strategies aimed at decreasing onset and progression of knee osteoarthritis in patients with CRF.     

Serum Inflammatory Biomarkers in Patients with Nonarteritic Anterior Ischemic Optic Neuropathy

PurposeTo evaluate the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) in patients with non-arteritic anterior ischemic optic neuropathy (NAION).MethodsFifty-six patients with NAION and 60 age-sex matched healthy controls were included in the study. Demographic characteristics and laboratory findings of the patients and the controls were obtained from the electronic medical records. NLR, PLR, MLR, and SII were calculated and compared between the groups. Cutoff values were also determined.ResultsNeutrophil, monocyte and platelet counts were higher in the NAION group than in the control group, but the difference was not statistically significant (p > 0.05). The mean NLR and SII were higher in the NAION group than in the control group (p = 0.004 and p = 0.011, respectively). In the receiver operating characteristic curve analysis, the areas under the curve for NLR were 0.67, and NLR >1.79 predicted NAION with a sensitivity of 71% and specificity of 59%. The areas under the curve for SII was 0.66, and SII of >417 predicted NAION with a sensitivity of 71% and specificity of 49%. There was no significant difference in PLR and MLR between the groups (p = 0.105 and p = 0.347, respectively).ConclusionsThe current study demonstrated that NAION patients had increased NLR and SII levels compared with control subjects. Elevated NLR and SII might serve as readily available inflammatory predictors in NAION patients.     

The effect of repetitive transcranial magnetic stimulation on refractory neuropathic pain in spinal cord injury

Objective

To investigate the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) on intractable neuropathic pain in patients with spinal cord injury (SCI).

Design

A single center, prospective, randomized, double-blinded, controlled study.

Setting

SCI rehabilitation unit of university rehabilitation center.

Participants

Seventeen patients with SCI and chronic neuropathic pain who met the inclusion criteria recruited between April 2010 and January 2012.

Interventions

Ten daily treatment sessions of real or sham rTMS (30 trains of 10-Hz stimuli for a duration of 5 seconds; a total of 1500 pulses at intensity equal to 110% of the resting motor threshold) was applied over vertex using a figure-of-8-shaped coil.

Outcome measures

Pain was assessed with visual analog scale (VAS) at baseline and 10 days, 6 weeks and 6 months after the treatment. Patients’ satisfactions obtained using a 5-point Likert scale at 6 months.

Results

Both real and sham rTMS provided a significant reduction in the VAS scores (real rTMS group, P = 0.004; sham rTMS group, P = 0.020). Post hoc analysis revealed the significant difference was at 10 days and 6 weeks compared to baseline in the real rTMS group and only at 10 days compared to baseline in the sham rTMS group. Comparison of VAS scores and patient satisfaction did not show any significant difference at each assessment point (P > 0.05).

Conclusion

Our results demonstrated analgesic effect of rTMS on intractable neuropathic pain in SCI was not superior to placebo. However, middle-term (over 6 weeks) pain relief by rTMS is encouraging and suggests the need for future studies with a larger sample size.     

Endoscopic management of gastric band erosions: a 7-year series of 14 patients

Background

Intragastric band migration is an unusual but major complication of gastric banding. We review our experience with endoscopic removal of eroded gastric bands.

Methods

We retrospectively evaluated the cases of 110 morbidly obese patients who underwent adjustable gastric banding between 2005 and 2012 to identify those who experienced band erosion. To remove the migrated band, we used an endoscopic approach with a Gastric Band Cutter.

Results

Band or tube erosion occurred in 14 patients (12.7%). The median time interval from the initial gastric band placement to the diagnosis of band erosion was 32 (range 18–52) months. Upper abdominal pain, port site infection, loss of restriction and weight regain were the most common symptoms. We used the Gastric Band Cutter to remove the band endoscopically. It was able to cut the band successfully in all but 1 patient, in whom twisting of the cutting wire required conversion from endoscopy to laparotomy. In 2 patients, the band, after being cut, was locked in the gastric wall and required laparotomic removal. In 1 patient, we performed surgery for intragastric penetration of the connecting tube broken close to the band.

Conclusion

The Gastric Band Cutter was successful in dividing the band in all but 1 patient, although we could not always complete the procedure endoscopically. Endoscopic removal seems to be effective and safe for band erosion.