Current advances in aptamer-assisted technologies for detecting bacterial and fungal toxins.

Infectious diseases are among the common leading causes of morbidity and mortality worldwide. Associated with the emergence of new infectious diseases, the increasing number of antimicrobial-resistant isolates presents a serious threat to public health and hospitalized patients. A microbial pathogen may elicit several host responses and use a variety of mechanisms to evade host defences. These methods and mechanisms include capsule, lipopolysaccharides or cell wall components, adhesions and toxins. Toxins inhibit phagocytosis, cause septic shock and host cell damages by binding to host surface receptors and invasion. Bacterial and fungal pathogens are able to apply many different toxin-dependent mechanisms to disturb signalling pathways and the structural integrity of host cells for establishing and maintaining infections Initial techniques for analysis of bacterial toxins were based on in vivo or in vitro assessments. There is a permanent demand for appropriate detection methods which are affordable, practical, careful, rapid, sensitive, efficient and economical. Aptamers are DNA or RNA oligonucleotides that are selected by systematic evolution of ligands using exponential enrichment (SELEX) methods and can be applied in diagnostic applications. This review provides an overview of aptamer-based methods as a novel approach for detecting toxins in bacterial and fungal pathogens.

Thymol and carvacrol strongly inhibit biofilm formation and growth of carbapenemase-producing Gram negative bacilli.

Discovery of novel drugs with new mechanisms of action and without cross-reaction with current therapeutic agents is crucial in the management of infections caused by multi-drug resistant (MDR) bacteria. The aim of the present study was to investigate effects of carvacrol and thymol on biofilm formation and antimicrobial activity against different carbapenemase-producing Gram negative bacilli. The antimicrobial and antibiofilm effect of thymol and carvacrol was investigated against strains harboring different genes related to carbapenemase resistance. Antimicrobial resistance was examined by an agar dilution method and antibiofilm effect was evaluated by microtiter plate assay and staining by crystal violet. Thymol and carvacrol had antibacterial effects ranging from 200-1600 µg/mL and 62-250 µg/mL respectively, and antibiofilm effect from 125-500 and 400-1600 µg/mL respectively. Seoul imipenemase- (SIM) producing isolates had the highest sensitivity, and NDM (New Delhi metallo-beta-lactamase) producing isolates had the lowest sensitivity to these components. Findings of the present study indicated a potential role of carvacrol and thymol in controlling carbapenemase-producing gram negative bacterial infections. These findings helped to develop herbal drugs for replacing antibiotics. In addition, their antibiofilm effects showed that carvacrol and thymol inhibit biofilm formation of carbapenemase-producing strains.

Effect of vitamin D on stress-induced hyperglycaemia and insulin resistance in critically ill patients.

AIM: Effects of vitamin D supplementation on the glycaemic indices and insulin resistance in diabetic and non-diabetic patients were studied. In this study, effects of vitamin D supplementation on stress-induced hyperglycaemia and insulin resistance were evaluated in non-diabetic surgical critically ill patients. METHODS: Adult surgical patients with stress-induced hyperglycaemia within the first 24 h of admission to the ICU were recruited. The patients randomly assigned to receive either vitamin D or placebo. Patients in the vitamin D group received a single dose of 600,000 IU vitamin D3 as intramuscular injection at time of recruitment. Besides demographic and clinical characteristics of the patients, plasma glucose, insulin, 25(OH) D and adiponectin levels were measured at the time of ICU admission and day 7. Homoeostasis model assessment for insulin resistance (HOMA-IR) and homestasis model assessment adiponectin (HOMA-AD) ratio were considered at the times of assessment. RESULTS: Comparing with the baseline, plasma 25(OH) D level significantly increased in the subjects who received vitamin D (p = 0.04). Improvement in fasting plasma glucose levels was detected in day 7 of the study compared with the baseline status in both groups. HOMA-IR showed a decrement pattern in vitamin D group (p = 0.09). Fasting plasma adiponectin levels increased significantly in the vitamin D group (p = 0.007), but not in the placebo group (p = 0.38). Finally, changes in HOMA-AD ratio were not significant in the both groups. CONCLUSION: Vitamin D supplementation showed positive effect on plasma adiponectin level, as a biomarker of insulin sensitivity in surgical critically ill patients with stress-induced hyperglycaemia. However, effects of vitamin D supplementation on HOMA-IR and HOMA-AD as indicators of insulin resistance were not significant.

Effects of aminoguanidine on infertile varicocelized rats: A functional and morphological study.

UNLABELLED: BACKGROUNDS AND THE PURPOSE OF THE STUDY: Inducible NO synthase activity has been frequently reported in varicose veins. Aminoguanidine is known to inhibit iNOS. The aim of this study was to examine the effects of aminoguanidine on varicocelized rats. METHODS: Male Wistar rats were divided into groups A, B, C, D, E, and F (control group). Groups A, B, C, and D rats underwent left varicocele induction with a 20-gauge needle. Group E (sham) rats underwent a similar procedure, but the renal vein was left intact. Ten weeks after varicocele induction, sperm parameters were evaluated in groups D, E, and F. Groups A and B received 50 mg/kg aminoguanidine or placebo, respectively, daily for 10 weeks. After 10 and 20 weeks of varicocele induction, the fertility outcomes of the experimental groups were evaluated. RESULTS: The values of the sperm parameters did not differ significantly between groups B and D, but were significant when compared with groups F and E (P≤0.05). The values of the sperm parameters of groups F and E showed no significant changes (P≤0.05). The changes between group A and groups B and D were significant (P≤0.05). Ten weeks after varicocele induction, rats of groups A, B, and C were still fertile. After 20 weeks, only half of the rats in group A were fertile. CONCLUSIONS: Aminoguanidine improved the sperm parameters and mating outcomes in vari-cocelized rats.

Spectrophotometric determination of lamotrigine in pharmaceutical preparations and urine by charge-transfer complexation.

Rapid and sensitive spectrophotometric methods are developed for the determination of lamotrigine (LTG) in pharmaceutical dosage forms and urine samples, based on the formation of the charge-transfer (CT) complexes between LTG as an n-donor and the acceptors: bromocresol green (BCG), bromocresol purple (BCP), and chlorophenol red (CPR). These complexes are studied spectrophotometrically in chloroform solution in order to obtain some information about their stoichiometry and stability of complexation. The analytical parameters and their effects on the extraction of drug from urine samples are investigated. The reactions were extremely rapid at room temperature, and the absorbance values remained unchanged after 24 h for all reactions. Beer's law was obeyed in the concentration ranges 0.15-19.8, 0.15-19.8 and 0.05-34.1 microg x ml(-1) for CPR, BCP and BCG, respectively. The proposed methods were applied successfully for the determination of LTG in pharmaceutical formulations, and human urine samples in the presence of other antiepileptic drugs such as carbamazepine, oxcarbazepine and phenobarbital, with good accuracy and precision.

Scalp metastasis from occult primary breast carcinoma: A case report and review of the literature.

BACKGROUND: Isolated distant cutaneous metastasis of breast carcinoma is uncommon. Furthermore, isolated metastasis of the scalp seems to be very rare in breast cancer. CASE PRESENTATION: A 44-year-old woman was referred to our dermatology department with concerns of a firm, painless, immobile, hardened, skin-colored mass fixed to the underlying tissues. The lesion measured 2 to 3 cm on the scalp frontalis without regional or distant lymphadenopathy. The patient had a history of benign right breast biopsy test results.Immunohistochemistry test results were positive for cytokeratin (AE1/AE3), cytokeratin 7, chromogranin, estrogen receptor, and gross cystic disease fluid protein-15; group PR/HER2 were both weakly positive. Cytokeratin 20, thyroid-lung transcription factor, S100 protein, vimentin and thyroglobulin were all negative. Pathology test results showed adenocarcinoma that was consistent with breast primary. CONCLUSION: Although cutaneous metastasis of the chest wall due to breast carcinoma is a common condition, scalp metastasis as the first sign of occult breast cancer is an extremely rare condition. We describe an isolated scalp metastasis as the initial presentation of breast cancer in a young woman in this report, which highlights that health care providers should be alert to the possibility that atypical soft tissue masses may represent a neoplasm. Further consideration of the scalp lesions among healthy looking patients is recommended.

Synthesis and Pharmacological Evaluation of New Chemical Entities from Ibuprofen as Novel Analgesic Candidates.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the first choice of drugs that are normally used for the treatment of pain and inflammation. Ibuprofen (I) and its analogues as the most widely used NSAIDs have been synthesized in recent years. In an effort to establish new candidates with improved analgesic properties, derivatives (II-VII) with substituted aromatic as well as aliphatic moieties were synthesized in this experiment and evaluated in formalin test with rats. The results were compared to ibuprofen and control groups. Findings indicated that derivatives with new alkylphenyl rings (VI and VII) had some similar or more analgesic activities relative to the control and ibuprofen groups, respectively; which could be justified as to more alkyl and phenyl groups instead of p-isobutylphenyl moiety in I.

Spectrophotometric study of cobalt, nickel, copper, zinc, cadmium and lead complexes with murexide in dimethylsulphoxide solution.

The complexation reactions between murexide and Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+) and Pb(2+) ions have been studied spectrophotometrically in dimethylsulphoxide solution at 25 degrees . The stoichiometry of the complexes was found to be 1:1. The stability constants of the complexes were determined, and found to follow the Irving-Williams rule for the cations of the first transition series. In dimethylsulphoxide solution, the complexes are much more stable than those in aqueous solution.

Spectrophotometric study of Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Pb(II) complexes with some crown ethers in dimethylsulphoxide solution using murexide as a metallochromic indicator.

The complexation reactions between Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Pb(II) ions and benzo-15-crown-5, dicyclohexyl-18-crown-6, dibenzo-18-crown-6 and 1,10-diaza-18-crown-6 have been studied in dimethylsulphoxide solution at 25 degrees by means of a competitive spectrophotometric method using murexide as a metallochromic indicator. With the exception of Pb(II)(benzo-15-croqn-5)(2) the stoichiometry of the resulting complexes was found to be 1:1. The formation constants of the complexes were determined, and found to follow the Irving-Williams rule for the cations of the first transition series. It was found that the metal ion-18-crown interactions are strongly dependent on the nature of the substituents on the ring.

The effect of low molecular weight heparin on survival in cancer patients: an updated systematic review and meta-analysis of randomized trials.

BACKGROUND: Tumors may exploit the coagulation system to enhance the survival and dissemination of cancer cells. Some studies have suggested that heparin and low molecular weight heparin (LMWH) have antitumor effects. We reported a previous meta-analysis that suggested a modest improvement in overall survival with the use of LMWH in patients with cancer. Herein, we present the results of an updated systematic review and meta-analysis. OBJECTIVE: To evaluate the effect of LMWH as compared with placebo or no anticoagulant on the overall survival in patients with solid cancers. METHODS: We conducted a systematic review and meta-analysis of randomized trials evaluating the use of LMWH vs. placebo or no anticoagulant in cancer patients without venous thrombosis. A meta-analysis was conducted with a random-effects model, and data were analyzed by the use of odds ratios (ORs) and relative risks (RRs) calculated for 1-year overall mortality. RESULTS: We identified 724 potentially relevant studies, nine of which met our inclusion criteria, and reported data on 1-year overall mortality. Studies were heterogeneous regarding types of cancer and interventions, and included 5987 patients, 98.4% of whom had advanced-stage disease (III and IV). There was no discernible effect on mortality with the use of LMWH (pooled OR 0.87, 95% CI 0.70-1.08; RR 0.94, 95% CI 0.86-1.04). CONCLUSIONS: In contrast to the previous study, these results did not show a survival benefit in cancer patients receiving LMWH. The effect of LMWH on overall survival in patients with limited-stage disease still is unknown.

[Conservative treatment of gastroduodenal peptic ulcer perforations: indications and results]. / Traitement conservateur des perforations peptiques gastroduodénales: indications et résultats.

Surgery is the conventional form of treatment for perforated peptic ulcer. Conservative treatment has however been described, and is still used in rare situations. The present study analyzes the indications and results of conservative therapy in our hospital. Between 1978 and 1995, 332 patients were admitted for perforated peptic ulcer. Twelve (3.5%), with a mean age of 85 (67-93) years, underwent conservative treatment (gastric suction, H2-blockers and broad-spectrum antibiotics). The diagnosis was established on the basis of epigastric pain and the finding of a pleuriperitoneum on the plain film of the abdomen. The indication for conservative treatment was a prohibitive anesthesiological risk in 11 patients and absence of peritoneal sign in one. The evolution was favourable only in 4 patients, who were discharged after a median stay of 18 days. Mortality was 8/12 patients. In one of these, autopsy showed ischemic colonic perforation. Conservative treatment of perforated peptic ulcer is associated with very high mortality. The results suggest that frequent and careful clinical monitoring is essential during the first 24 hours. In the event of deterioration, surgery must be reconsidered. In addition, the diagnosis should be confirmed by ruling out perforation of another abdominal organ.

[Lesions of hollow organs in closed abdominal trauma--the value of computerized tomography]. / Lésions d'organes creux dans le traumatisme fermé de l'abdomen--la valeur de la tomodensitométrie.

INTRODUCTION: evaluation of the clinical and radiological criteria for laparotomy in intestinal lacerations after a blunt abdominal trauma. Determination of the different radiological signs from the CT scan and the sensitivity of this examination in the diagnosis of intestinal lacerations. DESIGN: retrospective study. MATERIAL AND METHOD: we selected all patients operated for intestinal laceration caused by a blunt abdominal trauma during the period of 1986 to 1995. The clinical and radiological criteria for laparotomy in these patients were determined. Correlation of the radiological signs from the CT-Scan and the surgical findings was used to determine the sensitivity of the CT-scan. We distinguished patients who had an abdominal CT-scan from those patients for which no CT was done.

Delivery of FGF-2 but not VEGF by encapsulated genetically engineered myoblasts improves survival and vascularization in a model of acute skin flap ischemia.

Stimulating angiogenesis by gene transfer approaches offers the hope of treating tissue ischemia which is untreatable by currently practiced techniques of vessel grafting and bypass surgery. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) are potent angiogenic molecules, making them ideal candidates for novel gene transfer protocols designed to promote new blood vessel growth. In this study, an ex vivo gene therapy approach utilizing cell encapsulation was employed to deliver VEGF and FGF-2 in a continuous and localized manner. C(2)C(12) myoblasts were genetically engineered to secrete VEGF(121), VEGF(165) and FGF-2. These cell lines were encapsulated in hollow microporous polymer membranes for transplantation in vivo. Therapeutic efficacy was evaluated in a model of acute skin flap ischemia. Capsules were positioned under the distal, ischemic region of the flap. Control flaps showed 50% necrosis at 1 week. Capsules releasing either form of VEGF had no effect on flap survival, but induced a modest increase in distal vascular supply. Delivery of FGF-2 significantly improved flap survival, reducing necrosis to 34.2% (P < 0.001). Flap vascularization was significantly increased by FGF-2 (P < 0.01), with numerous vessels, many of which had a large lumen diameter, growing in the proximity of the implanted capsules. These results demonstrate that FGF-2, delivered from encapsulated cells, is more efficacious than either VEGF(121) or VEGF(165) in treating acute skin ischemia and improving skin flap survival. Furthermore, these data attest to the applicability of cell encapsulation for the delivery of angiogenic factors for the treatment and prevention of tissue ischemia.