Isolation and structure elucidation of new and unusual saxitoxin analogues from mussels

Chemical analyses of plankton and highly toxic mussel samples collected in eastern Canada during an intense bloom of the dinoflagellate Alexandrium tamarense established the presence of a complex mixture of paralytic shellfish poisoning (PSP) toxins. Application of a newly developed technique, hydrophilic interaction liquid chromatography-mass spectrometry, confirmed the identities of the known toxins and revealed the presence in the mussels of five saxitoxin analogues (M1-M5) that were not present in the plankton. Four of these compounds were isolated and their structures established by tandem mass spectrometry, 1D- and 2D-NMR spectroscopy, and chemical interconversion experiments. One of these was found to be 11beta-hydroxysaxitoxin (M2), while the other three were found to be new saxitoxin analogues, namely, 11beta-hydroxy-N-sulfocarbamoylsaxitoxin (M1), 11,11-dihydroxy-N-sulfocarbamoylsaxitoxin (M3), and 11,11-dihydroxysaxitoxin (M4). Compound M5 remains unidentified because of insufficient material for characterization.     

Smart Bone Graft Composite for Cancer Therapy Using Magnetic Hyperthermia

Magnetic hyperthermia (MHT) is a therapy that uses the heat generated by a magnetic material for cancer treatment. Magnetite nanoparticles are the most used materials in MHT. However, magnetite has a high Curie temperature (Tc~580 °C), and its use may generate local superheating. To overcome this problem, strontium-doped lanthanum manganite could replace magnetite because it shows a Tc near the ideal range (42–45 °C). In this study, we developed a smart composite formed by an F18 bioactive glass matrix with different amounts of Lanthanum-Strontium Manganite (LSM) powder (5, 10, 20, and 30 wt.% LSM). The effect of LSM addition was analyzed in terms of sinterability, magnetic properties, heating ability under a magnetic field, and in vitro bioactivity. The saturation magnetization (M_s) and remanent magnetization (M_r) increased by the LSM content, the confinement of LSM particles within the bioactive glass matrix also caused an increase in Tc. Calorimetry evaluation revealed a temperature increase from 5 °C (composition LSM5) to 15 °C (LSM30). The specific absorption rates were also calculated. Bioactivity measurements demonstrated HCA formation on the surface of all the composites in up to 15 days. The best material reached 40 °C, demonstrating the proof of concept sought in this research. Therefore, these composites have great potential for bone cancer therapy and should be further explored.     

Dual Pathology in a Patient with Right Lower Quadrant Pain

Meckel diverticula are remnants of the omphalomesenteric duct. They have 2% incidence in the general population, are usually asymptomatic, and tend to be diagnosed incidentally. The generally held principle had been that asymptomatic cases do not require resection, as exemplified by a 2008 systematic review of over 200 studies. However, a recent series reported an increased risk of malignancies, and recommended mandatory resection. We present a case of Meckel diverticulitis with concurrent infiltrative appendiceal carcinoid in a patient with right lower quadrant pain.     

Treatment of Late Class II Antibody-Mediated Rejection Status Postkidney Transplantation: Two Case Reports

We are describing the successful treatment of two cases of late Class II antibody mediated rejection status postkidney transplantation. The first patient was treated with a combination of plasmapheresis, intravenous immunoglobulin (IVIG), and stenting of the transplanted renal artery. The second was treated with IVIG and pulse steroids.     

An analysis of men with clinically localized prostate cancer who deferred definitive therapy

PURPOSE: We evaluated expectant management of prostate cancer with definitive treatment deferred until evidence of cancer progression in men with low risk, localized cancers. MATERIALS AND METHODS: We retrospectively reviewed prospectively entered data base records. Patients with low risk cancer who were eligible for definitive therapy but chose deferred management between 1984 and 2001 composed the cohort. Followup included regular evaluations to detect progression by prostate specific antigen (PSA), digital rectal examination, transrectal ultrasound and prostate biopsy. Objective progression was defined by a point scale of changes in prognostic factors. Definitive treatment was recommended in patients with objective progression. RESULTS: The cohort comprised 88 patients with clinical stages T1-2, NX0, M0 prostate cancer, a mean age of 65.3 years and a mean initial PSA of 5.9 ng/ml. Systematic biopsy, which was repeated after the initial diagnostic biopsy, showed no cancer in 61% of cases. During a median followup of 44 months 22 patients had progression. Factors that predicted progression were repeat biopsy showing cancer (p = 0.004) and initial PSA (p = 0.014). Actuarial 5 and 10-year progression-free probabilities were 67% and 55%, respectively. Of the 31 patients treated 17 underwent radical prostatectomy, 13 received radiation therapy and 1 received androgen ablation. Seven men who did not show objective progression were treated because of anxiety. Only 1 patient, who was treated with radiation therapy, had biochemical recurrence. CONCLUSIONS: Deferred therapy may be a feasible alternative to curative treatment in select patients with favorable, localized prostate cancer. About half of these patients remain free of progression at 10 years and definitive treatment appeared effective in those with progression. Absent cancer on repeat needle biopsy identified cases highly unlikely to progress.     

Giant cell tumor and Paget's disease of bone in one family: geographic clustering

Giant cell tumor is a rare complication of Paget's disease of bone. Typically, this tumor occurs in the case of polyostotic disease and only in pagetic bones. This tumor rarely has been seen in multiple family members who have Paget's disease, although Paget's bone disease clearly has a hereditary component. Our report documents four cases of polyostotic Paget's bone disease complicated by benign giant cell tumor. In two patients, the giant cell tumor also was multifocal. All patients were from one family. They were born in Avellino and reside in Campania, a Southern Italian region. The ancestors of the patients with familial giant cell tumor in Paget's bone disease were born in the same geographic area. These data suggest that a combination of environmental and genetic factors could be responsible for linkage of the patients born in Avellino with this neoplasm that is highly unusual in patients with Paget's disease of bone.     

Absence of donor CD40 protects renal allograft epithelium and preserves renal function

Blocking the CD40‐CD154 pathway prevents allograft rejection and induces donor‐specific tolerance in various experimental models. However, the translation to clinical studies has been hampered by unexpected thromboembolic complications of CD154‐blocking antibodies. Thus, blocking CD40 instead is now considered as an alternative strategy. Here, we evaluated the role of donor CD40 in allospecific T‐cell responses in vitro and in an in vivo model for renal transplantation. Fully MHC‐mismatched allografts from CD40‐deficient donors displayed better renal function than wild type. These functional data correlated with a lower level of apoptosis in renal tubular epithelial cells and higher expression of PD‐L1, which is most probably because of a reduced Th17 response in recipients of a CD40‐deficient donor. This hypothesis was supported in vitro, where donor CD40 expression was important for the induction of direct allospecific T‐cell responses. Especially the induction of Th17 cells was critically dependent on donor CD40. IL‐17A in conjunction with interferon‐γ in turn rendered renal tubular epithelial cells to a more costimulatory state by upregulating CD40 and downregulating PD‐L1 expression. In conclusion, CD40 blockade not only reduces the allospecific T‐cell responses, but might also lead to protection of tubular epithelium from apoptosis and thereby preserve kidney allograft function.     

Deep Venous Thrombosis in Lap Band Surgery: A Single Center Study

Bariatric surgery has been demonstrated to be an effective treatment for morbid obesity. The purpose of this study is to investigate the incidence of pre- and post-operative deep venous thrombosis (DVT) in Lap-Band surgical patients. This study group comprised 56 consecutive patients who underwent Lap-Band surgery. Mean age and body mass index were 38 years (range: 18–64 years) and 50.9 kg/m² (range: 53–74 kg/m²), respectively. All the patients were screened with duplex ultrasonography pre- and post-operatively. There were no iliac, femoral, or popliteal vein thromboses detected at any given point of time. No patient had any clinical signs or symptoms of DVT post-operatively. There were no observable differences attributable to DVT prophylaxis. This data suggest that in the setting of chemical and mechanical prophylaxis, the incidence of DVT in patients undergoing Lap-Band surgery at an established bariatric centre is minimal.