Misdiagnosis of diabetic foot ulcer in patients with undiagnosed skin malignancies.

A growing number of studies report dermal malignancies mimicking diabetic foot ulcers (DFUs). We reviewed clinical cases reporting malignant tumours misdiagnosed to be DFU aiming to identify factors contributing to misdiagnosis. We systematically searched in PubMed for clinical cases reporting on misdiagnosis of DFU in patients with cancer. A chi-square analysis was conducted to show the link between the incidence of initial DFU misdiagnosis and patient age, gender and wound duration. Lesions misdiagnosed to be DFU were subsequently diagnosed as melanoma (68% of the cases), Kaposi's sarcoma (14%), squamous cell carcinoma (11%), mantle cell lymphoma, and diffuse B-cell lymphoma (both by 4%). Older age (≥65 years) was associated with a significantly increased risk of malignancy masked as DFU (OR: 2.452; 95% CI: 1.132 to 5.312; P value = .019). The risk of such suspicion in older patients (age ≥ 65 years) was 145% higher than in younger patients (age < 65 years). Clinicians should maintain a high level of awareness towards potentially malignant foot lesions in elderly patients with diabetes (age ≥ 65).

Human endometrial stem cells: High-yield isolation and characterization.

BACKGROUND: Menstrual blood is only recently and still poorly studied, but it is an abundant and noninvasive source of highly proliferative mesenchymal stromal cells (MSCs). However, no appropriate isolation method has been reported due to its high viscosity and high content of clots and desquamated epithelium. METHODS: We studied three different isolation approaches and their combinations: ammonium-containing lysing buffer, distilled water and gradient-density centrifugation. We tested the proliferative capacity, morphology, surface markers and pluripotency of the resulting cells. RESULTS: Our isolation method yields up to four million nucleated cells per milliliter of initial blood, of which about 0.2-0.3% are colony-forming cells expressing standard mesenchymal markers CD90, CD105 and CD73, but not expressing CD45, CD34, CD117, CD133 or HLA-G. The cells have high proliferative potential (doubling in 26 h) and the ability to differentiate into adipocytes and osteocytes. Early endometrial MSCs (eMSCs) express epithelial marker cytokeratin 7 (CK7). CK7 is easily induced in later passages in a prohepatic environment. We show for the first time that a satisfactory and stable yield of eMSCs is observed throughout the whole menstrual period (5 consecutive days) of a healthy woman. DISCUSSION: The new cost/yield adequate method allows isolation from menstrual blood a relatively homogenous pool of highly proliferative MSCs, which seem to be the best candidates for internal organ therapy due to their proepithelial background (early expression of CK7 and its easy induction in later passages) and for mass cryobanking due to their high yield and availability.

A Novel Lipopeptaibol Emericellipsin A with Antimicrobial and Antitumor Activity Produced by the Extremophilic Fungus Emericellopsis alkalina.

Soil fungi are known to contain a rich variety of defense metabolites that allow them to compete with other organisms (fungi, bacteria, nematodes, and insects) and help them occupy more preferential areas at the expense of effective antagonism. These compounds possess antibiotic activity towards a wide range of other microbes, particularly fungi that belong to different taxonomical units. These compounds include peptaibols, which are non-ribosomal synthesized polypeptides containing non-standard amino acid residues (alpha-aminoisobutyric acid mandatory) and some posttranslational modifications. We isolated a novel antibiotic peptide from the culture medium of Emericellopsis alkalina, an alkalophilic strain. This peptide, called emericellipsin A, exhibited a strong antifungal effect against the yeast Candida albicans, the mold fungus Aspergillus niger, and human pathogen clinical isolates. It also exhibited antimicrobial activity against some Gram-positive and Gram-negative bacteria. Additionally, emericellipsin A showed a significant cytotoxic effect and was highly active against Hep G2 and HeLa tumor cell lines. We used NMR spectroscopy to reveal that this peptaibol is nine amino acid residues long and contains non-standard amino acids. The mode of molecular action of emericellipsin A is most likely associated with its effects on the membranes of cells. Emericellipsin A is rather short peptaibol and could be useful for the development of antifungal, antibacterial, or anti-tumor remedies.

Pharmacokinetic Properties of the Novel Synthetic Cannabinoid 5F-APINAC and Its Influence on Metabolites Associated with Neurotransmission in Rabbit Plasma.

The strong psychoactive effects of synthetic cannabinoids raise the need for the deeper studying of their neurometabolic effects. The pharmacokinetic properties of 5F-APINAC and its influence on metabolomics profiles associated with neurotransmission were investigated in rabbit plasma. Twelve rabbits divided into three groups received 1-mL 5F-APINAC at 0.1, 1 and 2 mg/kg. The intervention groups were compared with the controls. Sampling was performed at nine time points (0-24 h). Ultra-high-performance liquid chromatography-tandem mass spectrometry was used. The pharmacokinetics were dose-dependent (higher curve at a higher dose) with a rapid biotransformation, followed by gradual elimination within 24 h. The tryptophan concentrations abruptly decreased (p < 0.05) in all tested groups, returning to the basal levels after 6 h. 5-hydroxylindole acetic acid increased (p < 0.05) in the controls, but this trend was absent in the treated groups. The aspartic acid concentrations were elevated (p < 0.001) in the treated groups. L-kynurenine was elevated (p < 0.01) in the intervention groups receiving 1 mg/kg to 2 mg/kg. Dose-dependent elevations (p < 0.01) were found for kynurenic acid, xanthurenic acid and quinolinic acid (p < 0.01), whereas the anthranilic acid trends were decreased (p < 0.01). The indole-3-propionic acid and indole-3-carboxaldehyde trends were elevated (p < 0.05), whereas the indole-3-lactic acid trajectories were decreased (p < 0.01) in the intervention groups. 5F-APINAC administration had a rapid biotransformation and gradual elimination. The metabolites related to the kynurenine and serotonergic system/serotonin pathways, aspartic acid innervation system and microbial tryptophan catabolism were altered.

Plasma Sarcosine Measured by Gas Chromatography-Mass Spectrometry Distinguishes Prostatic Intraepithelial Neoplasia and Prostate Cancer from Benign Prostate Hyperplasia.

OBJECTIVE: Sarcosine was postulated in 2009 as a biomarker for prostate cancer (PCa). Here, we assess plasma sarcosine as a biomarker that is complementary to prostate-specific antigen (PSA). METHODS: Plasma sarcosine was measured using gas chromatography-mass spectrometry (GC-MS) in adults classified as noncancerous controls (with benign prostate hyperplasia [BPH], n = 36), with prostatic intraepithelial neoplasia (PIN, n = 16), or with PCa (n = 27). Diagnostic accuracy was assessed using receiver operating characteristic curve analysis. RESULTS: Plasma sarcosine levels were higher in the PCa (2.0 µM [1.3-3.3 µM], P <.01) and the PIN (1.9 µM [1.2-6.5 µM], P <.001) groups than in the BPH (0.9 µM [0.6-1.4 µM]) group. Plasma sarcosine had "good" and "very good" discriminative capability to detect PIN (area under the curve [AUC], 0.734) and PCa (AUC, 0.833) versus BPH, respectively. The use of PSA and sarcosine together improved the overall diagnostic accuracy to detect PIN and PCa versus BPH. CONCLUSION: Plasma sarcosine measured by GC-MS had "good" and "very good" classification performance for distinguishing PIN and PCa, respectively, relative to noncancerous patients diagnosed with BPH.

Extension of Maximal Lifespan and High Bone Marrow Chimerism After Nonmyeloablative Syngeneic Transplantation of Bone Marrow From Young to Old Mice.

The goal of this work was to determine the effect of nonablative syngeneic transplantation of young bone marrow (BM) to laboratory animals (mice) of advanced age upon maximum duration of their lifespan. To do this, transplantation of 100 million nucleated cells from BM of young syngeneic donors to an old nonablated animal was performed at the time when half of the population had already died. As a result, the maximum lifespan (MLS) increased by 28 ± 5%, and the survival time from the beginning of the experiment increased 2.8 ± 0.3-fold. The chimerism of the BM 6 months after the transplantation was 28%.