Monocyte implication in renal allograft dysfunction

Macrophages are involved in the development and progression of kidney fibrosis. The aim of this study was to analyse the phenotype of circulating monocytes and their ability to predict kidney allograft dysfunction in living kidney transplant recipients. Whole blood samples from 25 kidney recipients and 17 donors were collected at five time‐points. Monocyte phenotype was analysed by flow cytometry, and interleukin (IL)‐10 and soluble CD163 by enzyme‐linked immunosorbent assay. One week after transplantation, surface CD163 and IL‐10 levels increased significantly from baseline [2·99 ± 1·38 mean fluorescence intensity (MFI) to 5·18 ± 2·42 MFI for CD163; 4·5 ± 1·46 pg/ml to 6·7 ± 2·5 pg/ml for IL‐10]. This CD163 increase correlated with 4‐month creatinine levels (r = 0·4394, P = 0·04). However, soluble CD163 decreased significantly from baseline at 1 week (797·11 ± 340·45 ng/ml to 576·50 ± 293·60 ng/ml). CD14⁺CD16^– monocytes increased at 4 months and correlated positively with creatinine levels at 12 and 24 months (r = 0·6348, P = 0·002 and r = 0·467, P = 0·028, respectively) and negatively with Modification of Diet in Renal Disease (MDRD) at 12 months (r = 0·6056, P = 0·003). At 4 months, IL‐10 decreased significantly (P = 0·008) and correlated positively with creatinine at 2 years (r = 0·68, P = 0·010) and with CD14⁺CD16^– monocytes at 4 months (r = 0·732, P = 0·004). At 24 h, levels of human leucocyte antigen D‐related declined from 12·12 ± 5·99 to 5·21 ± 3·84 and CD86 expression decreased from 2·76 ± 1·08 to 1·87 ± 0·95. Both markers recovered progressively until 12 months, when they decreased again. These results indicate that monitoring monocytes could be a promising new prognostic tool of graft dysfunction in renal transplant patients.     

Detection of occult cerebrospinal fluid involvement during maintenance therapy identifies a group of children with acute lymphoblastic leukemia at high risk for relapse

We aimed at assessing the clinical significance of the levels of acute lymphoblastic leukemia (ALL) cells in samples of cerebrospinal fluid (CSF) during therapy. We studied 990 CSF samples from 108 patients, at the time of diagnosis (108) and at each time of intrathecal therapy (882). The proportions of leukemic cells in CSF samples were assessed by flow cytometry (FCM). Patients with central nervous system (CNS) involvement at diagnosis (FCM+) showed predominantly a T‐ALL, and higher percentages of known negative prognostic factors: high risk group, higher white blood cell counts, normal karyotype, and the BCR‐ABL fusion gene. No differences in relapse free survival (RFS) and overall survival (OS) were observed between FCM+ versus FCM? at diagnosis. Patients with CNS involvement during therapy showed significantly older age, and higher frequencies of T‐cell leukemia. We found a significantly higher RFS in patients with FCM+ during therapy. The detection of subclinical CNS disease by FCM during maintenance was associated with significantly lower 3‐years RFS and 3‐years OS. A sensitive methodology like FCM can be applied for a close follow‐up of the levels of ALL in CFS samples, and may identify a group of patients at high risk for relapse. Am. J. Hematol. 88:359–364, 2013. © 2013 Wiley Periodicals, Inc.     

Antimicrobial Activity of Medicinal Plants from Baja California Sur (México)

Ethanol extracts of 109 plants reported to be used in the traditional medicine of Baja California Sur (México) were tested for antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Streptococcus faecalis, Escherichia coli and Candida albicans. Of these, 64 were active against one or more test organisms.     

Screening Of Marine Organisms For Antimicrobial And Antiprotozoal Activity

Ethanol extracts from a group of 53 marine organisms, including a newly identified species, from Baja California Sur (México), were evaluated for their antimicrobial and antiparasitic activity. The activity against Staphylococcus aureus, Streptococcus faecalis, Bacillus subtilis (Gram +), Escherichia coli (Gram-) and Candida albicans (yeast) was determined by the diffusion agar method. Aplysina gerardogreeni (Demospongiae) was found to be the most active sample. In addition, A. gerardogreeni, Pacifigorgia media, and Pacifigorgia sp. possess significant activity against Mycobacterium tuberculosis H 37 Rv and Pacifigorgia media and Geodia sp. against Mycobacterium avium. From this group, 15 ethanol extracts were tested in vitro against Entamoeba histolytica and Giardia lamblia. Litotamnium crassiussculum, Geodia sp., Pacifigorgia sp. showed significant activity against Entamoeba histolytica while Myxilla incrustans and Muricea appressa were active against Giardia lamblia. Litotamnium crassiussculum showed activity against both trophozoites.     

Heart Failure as First Sign of Development of Cardiac Metastases in a Patient with Diagnosis of Papillary Thyroid Carcinoma on Treatment with Tyrosine-Kinase Inhibitors: Differential Diagnoses and Clinical Management

Background

Cardiac metastases from papillary thyroid carcinoma are very uncommon. Their incidence is rising due to improvements in survival and diagnosis; nevertheless, our patient is the fourth case reported up to date. There are no clinical trials available in this scenario. Therefore, treatment choice is made based on clinical experience and case reports; notably, the largest case report series was prior to the approval for using tyrosine-kinase inhibitors in thyroid cancer.

Patient

A 73-year-old lady had dedifferentiated papillary thyroid cancer with ongoing sorafenib. After 9 months on this treatment, she presented with dyspnea and heart failure. Differential diagnosis included infection, progression of disease and cardiotoxicity. After a comprehensive assessment (echocardiography, computed tomography, PET, magnetic resonance), we found progression of lung disease, and the appearance of heart metastases.

Results

After recovering from the basal status, she started on second-line treatment with sunitinib, which was well-tolerated. She achieved stable disease with a decrease in tumor marker levels.

Conclusions

We should include cardiac metastases in the differential diagnosis of heart failure in cancer patients. Magnetic resonance imaging is the gold standard for assessment. Sorafenib is the mainstay of the first-line therapy in metastatic thyroid cancer, achieving long-term disease control with good tolerance. Sunitinib could be a safe second-line treatment option (not cardiotoxicity related) with promising results. Therefore, our report presents a sequence of treatment with tyrosine-kinase inhibitors in metastatic thyroid carcinoma with an encouraging outcome, which deserves further investigation.Key Words: Thyroid cancer, Cardiac metastases, Sorafenib, Sunitinib, Tyrosine-kinase inhibitors, Cardiac magnetic resonance     

Pyrazoles and pyrazolines as neural and inducible nitric oxide synthase (nNOS and iNOS) potential inhibitors (III)

We have previously described a series of 4,5-dihydro-1H-pyrazole as moderately potent nNOS inhibitors. As a follow up of these studies, we report here the preparation and the preliminary evaluation of a series of 1-alkyl-3-benzoyl-4,5-dihydro-1H-pyrazole and 1-alkyl-3-benzoyl-1H-pyrazole as potential inhibitors of both neuronal and inducible nitric oxide synthases (nNOS and iNOS). None of the reported compounds exhibited significant iNOS or nNOS inhibition, although the 1-benzyl-3-(2-amino-5-chlorobenzoyl)-1H-pyrazole-5-carboxylic acid ethyl ester derivative (10l), which shows an inhibition of 50% versus iNOS at a 1mM final concentration and no activity against nNOS, is potentially amenable of further optimization. The reasons for the inactivity of the reported series are discussed on the basis of docking studies.     

Factores de riesgo cardiovascular: estudio de seguimiento en población no diabética

ObjectivesTo evaluate the cardiovascular risk factors (CVRF), their relationship with insulin resistance (IR) and pancreatic beta-cell (PBC) function in a known non-diabetic population, and to follow its progress over a period of 5 years.DesignNested case-control study developed in two phases: the identification and characterisation of the cohort to study and the follow up.SettingUrban Primary Care Centre.ParticipantsA non-diabetic population sample from 40 to 70 years.Main measurementsHistory of CVRF, physical examination (body mass index, abdominal girth, blood pressure), laboratory tests (fasting glucose, lipid profile and fasting insulin) and calculation of IR and PBC using the Homeostasis Model Assessment mathematical program.ResultsIdentification phase: 326 subjects. CVRF 32.5% dyslipaemia, 28.8% smoking, 28.2% obesity and 24.8% increased blood pressure. Number of CVRF: 37.7% had one, 21.5% two, 10.1% three and 2.1% four. Relationship between number of CVRF and IR. More IR in hypertensive, obese and dyslipaemic subjects. Follow up phase (5 years): 121 subjects. Significant proportion of dyslipaemia and impaired fasting glucose (IFG).ConclusionsThe most common CVRF were dyslipaemia, smoking, obesity and raised blood pressure, with more IR in patients with high blood pressure, dyslipaemia and obesity and a higher number of CVRF in comparison with the rest of the population. At five years of follow up, an increase was only observed in the number of dyslipaemia and IFG and no reduction was achieved in the percentage of active smokers.