Bioactive rearranged and halogenated semisynthetic derivatives of the marine natural product sarcophine

Cembranoids are natural diterpenes with 14-membered macrocyclic rings. The simplest natural cembranoid, (+)-cembrene, was isolated from pine oleoresin. Sarcophytols A and B are known cembranoids that inhibit tumor promotion. Sarcophine is a related cembranoid isolated from the Red Sea soft coral Sarcophyton glaucum. Sarcophine and its bioconversion products and semisynthetic derivatives are reported to possess cancer chemopreventive activity. Oxymercuration-demercuration of sarcophine using Hg(OAc)2 and NaBH4 afforded four new rearranged and hydroxylated products. Bromination of sarcophine with N-bromosuccinimide (NBS) furnished two new brominated and rearranged products. Reaction with iodine gave the known iso-sarcophinone and (+)-sarcophytoxin B. Structure elucidation was based on a combination of transition state modeling, molecular dynamics, mechanistic considerations, and 2D NMR data. The antiproliferative activity of the new products is also reported.     

The long-term outcome of the endoscopic subureteric implantation of polydimethylsiloxane for treating vesico-ureteric reflux in children: a retrospective analysis of the first 195 consecutive patients in two European centres

OBJECTIVE: To determine the long-term efficacy of endoscopically implanting polydimethylsiloxane (PDS, Macroplastique, Uroplasty BV, Geleen, the Netherlands) for treating vesico-ureteric reflux (VUR) in children. PATIENTS AND METHODS: We retrospectively reviewed the records of 195 children treated with PDS over the past 10 years in two European centres (Netherlands and UK) and conducted follow-up investigations where deemed necessary. In the Dutch centre patients were treated according to a prospective approved study protocol. RESULTS: Of the 195 treated children, 155 had a successful outcome; in all, 311 refluxing renal units were treated, with an overall success rate of 82.3% in a mixed group of patients with unilateral or bilateral VUR and duplex systems. CONCLUSION: The long-term data from these two independent centres confirms the viability of PDS and the technique for treating VUR in children. We conclude that the material is safe and effective and can be used in VUR grades II-V. Treating patients with grade I VUR is recommended in those cases where there is no spontaneous resolution and 'breakthrough' infections.     

Secretin in a patient with treatment-resistant schizophrenia and prominent autistic features

Secretin, a gastrointestinal (GI) peptide, may offer therapeutic benefit in autism. Autistic features can also be present in schizophrenia and a recent study suggested a role for adjunctive secretin in treatment-resistant schizophrenia. The current report describes one patient with undifferentiated schizophrenia and prominent autistic features who received a single dose of secretin and demonstrated substantial yet transient improvement. The case illustrates the potential role of secretin as a novel adjunctive treatment strategy in schizophrenic patients with autistic features.     

Conductive hearing loss: investigation of possible inner ear origin in three cases studies

This is a report of three cases of mixed hearing loss that resulted from inner ear disorders. Two cases were unilateral and the third was bilateral. The diagnosis was based on the findings of normal middle and external ears in association with the absence of round window reflexes. The contralateral stapedial reflex was present in the two unilateral cases. This is the first documentation of conductive deafness due to inner ear abnormality. This diagnosis should be considered in cases of conductive hearing loss if the middle and external ears are normal. More studies are needed to establish the pathophysiology of this entity.     

Indium-111-octreotide scintigraphy,intraoperative gamma-detector localisation and somatostatin receptor expression in primary human breast cancer

12 women with primary breast cancer underwent somatostatin receptor scintigraphy (SRS) with ¹¹¹In-DTPA-D-Phe¹-octreotide. The tumour sizes varied between 2 and 5 cm and were all, except one, palpable at clinical examination. Tumour biopsies were taken with additional sampling from normal breast tissue, fat, muscle, axillary lymph nodes and peripheral blood. Ratios between the ¹¹¹In activity concentration in the tissue biopsies (Ti) and in peripheral blood (B) as well as in normal breast tissue (Br) were calculated. In 8/12 patients the scintillation detector was used intraoperatively for radioactivity measurements of the biopsies in situ and ex vivo. The sstr-subtype profiles were determined by northern blot analysis and the relative expression of sstr2 by ribonuclease protection assay (RPA) and immunocytochemistry. Preoperative SRS visualised all primary breast cancer tumours. The scintigraphic image showed no correlation with the histopathological type of the tumour or with the abundance of oestrogen/progesterone receptors on the tumour. Two patients with a massive tumour infiltration of the lymph nodes had a distinct positive SRS of the ipsilateral axilla. In one patient with three nodal metastases the scintigraphic image of the axilla was weak but visible. Four other patients with a negative axillary scintigraphy had 1–2 lymph node metastases. The Ti/B ratios for the breast tumours varied between four and 33 and were not different from Ti/Br ratios. In lymph node metastases the Ti/B ratios were higher (10–41). Intraoperative detector measurements showed a significant difference between the breast tumour and normal tissue in 2/8 patients in situ. Similar measurements on excised tissues (ex vivo) showed a significant difference in 6/8 patients. Two patients with lymph node metastases exhibited a significantly increased uptake ex vivo by detector measurements, but in only one of them in situ. All tumour biopsies expressed the presence of sstr1, 3, 4 and 5, but not of sstr2 at northern analysis. On the other hand, sstr2 was detected in all tumours by RPA and immunocytochemistry. Preoperative SRS visualised primary breast cancer lesions in all 12 patients. SRS could also demonstrate extensive axillary tumour infiltration. Intraoperative use of the scintillation detector could not exclude axillary metastases in situ. The low Ti/B values of both primary tumours and metastases indicate limitations of the radiopharmaceutical used.     

A pseudoguaiane sesquiterpene xylopyranoside from Echinops hussoni

A new pseudoguaiane sesquiterpene xylopyranoside ester, named echusoside (1), was isolated from the aerial parts of Echinops hussoni Boiss. (Asteraceae) collected from the southeastern border of Egypt. The structure elucidation of echusoside was based primarily on 1D, 2D-NMR analyses and chemical derivatization. This is the first report for a pseudoguainane sesquiterpene in the genus Echinops.     

Steinstrasse after extracorporeal shockwave lithotripsy: aetiology, prevention and management

OBJECTIVE: To determine the causes of steinstrasse, methods of prevention and treatment strategies. PATIENTS AND METHODS: Fifty-two patients with steinstrasse were identified and treated: all patients were initially treated conservatively but when there was obstruction, infection or no progression of the stone fragments, further treatment was used, ranging from repeated extracorporeal shockwave lithotripsy (ESWL), percutaneous nephrostomy (PCN), endoscopic manipulations and finally open surgery, depending on the degree of obstruction, infection, renal function and response to each kind of therapy. RESULTS: Conservative management was successful in 25 patients (48%), repeated ESWL in 12 (23%), PCN in 10 (19%), ureteroscopy in three (6%) and open surgery in two (4%). CONCLUSION: As many patients, and particularly those with larger stones, are treated by ESWL, the risk of developing steinstrasse will increase, with associated patient discomfort, infection or impaired renal function. The optimum selection of cases (aiming to pulverize the stones rather than fragment them) and accurate stone targeting are essential to minimise the development of steinstrasse. The meticulous follow-up of patients with steinstrasse should prevent any loss of renal function. When there is obstruction and/or infection or renal damage, active treatment is indicated, of which ESWL and PCN are the most effective, with ureteroscopy and open surgery reserved for difficult cases.     

New quinoline alkaloids from Ruta chalepensis

The roots of Ruta chalepensis, collected from the northern Saudi desert, yielded two new quinoline alkaloids, namely, 2-?6'-(2H-benzo[d]1' ',3' '-dioxolen-5' '-yl)hexyl?-hydroquinolin-4-one (1) and 2-?6'-(2H-benzo[d]1' ',3' '-dioxolen-5' '-yl)hexyl?-4-methoxy-quinoline (2). Nine previously reported alkaloids, dictamnine, pteleine, skimmianine, rutacridone, isogravacridonechlorine, maculosidine, graveoline, graveolinine, and 4-methoxy-1-methyl-2(1H)-quinolinone, and coumarins, chalepensin, and umbelliferone were also isolated. Structure elucidations were based primarily on 1D and 2D NMR analyses and chemical transformations. Antimicrobial activity of these compounds is discussed.     

Bioactive 12-oleanene triterpene and secotriterpene acids from Maytenus undata

The aerial parts of Maytenus undata yielded four new 12-oleanene and 3,4-seco-12-oleanene triterpene acids, namely, 3-oxo-11alpha-methoxyolean-12-ene-30-oic acid (1), 3-oxo-11alpha-hydroxyolean-12-ene-30-oic acid (2), 3-oxo-olean-9(11), 12-diene-30-oic acid (3), and 3,4-seco-olean-4(23),12-diene-3, 29-dioic acid (20-epi-koetjapic acid) (5), together with the known 3, 11-dioxoolean-12-ene-30-oic acid (3-oxo-18beta-glycyrrhetinic acid) (4), koetjapic acid (6), and the 12-oleanene artifact 3-oxo-11alpha-ethoxyolean-12-ene-30-oic acid (7). Koetjapic acid (6) inhibited the growth of Staphylococcus aureus, methicillin-resistant S. aureus, and Pseudomonas aeruginosa, with an MIC range of 3.125-6.25 microg/mL. The new 3,4-secotriterpene acid 20-epi-koetjapic acid (5) potently inhibited rat neonatal brain microglia phorbol ester-stimulated thromboxane B(2) (IC(50) = 0.5 microM) and superoxide anion (IC(50) = 1.9 microM) generation.