On the Edge of the Known: Extremely Electron-Rich (Di)Carboranyl Phosphines.

The syntheses of the first B9-connected carboranylphosphines (B9-Phos) featuring two carboranyl moieties as well as access to B9-Phos ligands with bulky electron-donating substituents, previously deemed unattainable, is reported. The electrochemical properties of the B9-Phos ligands were investigated, revealing the ability of the mesityl derivatives to form stabilized phosphoniumyl radical cations. The B9-Phos ligands display an extremely electron-releasing character surpassing that of alkyl phosphines and commonly used N-heterocyclic carbenes.

Phosphorus guiding palladium: [4 + 4] metallomacrocyclic Pd complex and self-assembly of heterometallic Pd/Zn grid-type complex.

The reaction of heteroditopic ligand 1 featuring a hard pyridine-hydrazone-pyrimidine (N,N,N) site and a softer pyrimidine-hydrazone-phosphane (N,N,P) pocket with [Pd(CHCN)](OTf) in different metal-to-ligand ratios (M : L) gave the homobimetallic Pd complex [Pd(1)(CHCN)](OTf) (2, M : L ratio 2 : 1), the [4 + 4] metallomacrocyclic Pd complex [Pd(1)](OTf) (3, M : L ratio 1 : 1) and the monometallic complex [Pd(1)](OTf) (4, M : L ratio 1 : 2). The soft N,N,P pocket preferably coordinates Pd, while the harder N,N,N coordination site selectively binds Zn forming the homoleptic meridional "corner" complexes [Zn(1)](OTf) (5) and [PdZn(1)](OTf) (6). The distinctive coordination behavior of ligand 1 is highlighted by the self-assembly of the heterometallic Pd/Zn grid-type complex [PdZn(1)](OTf) (7) in a one-pot reaction.

Heterobimetallic Pd/Mn and Pd/Co complexes as efficient and stereoselective catalysts for sequential Cu-free Sonogashira coupling-alkyne semi-hydrogenation reactions.

A series of heterobimetallic Pd/M complexes (M = Mn, Co) were synthesised and tested as precatalysts for sequential Sonogashira coupling-alkyne semi-hydrogenation reactions to form -aryl alkenes. The carbometalated heterobimetallic Pd/Co complex CoPdL3' demonstrated an apparent cooperative effect compared to the corresponding monometallic counterparts. This compound was identified as a potent single-molecule catalyst for the one-pot Cu-free Sonogashira coupling of aryl bromides with terminal alkynes followed by chemo- and stereoselective semi-hydrogenation of the alkyne intermediate using NH·BH as a hydrogen source.

Palladium Goes First: A Neutral Asymmetric Heteroditopic , Ligand Forming Pd-3d Heterobimetallic Complexes.

A facile two-step synthesis of bis(1-methylhydrazinyl)pyrimidine from pyridine-2-carbaldehyde and 2-diphenylphosphanylbenzaldehyde gave access to the new asymmetric ligand . The phosphane selectively guides Pd into the softer tridentate ,, pocket, yielding monometallic complex . A second reaction with a 3d transition metal complex precursor (groups 7 to 12) fills the vacant ,, pocket and thus provides a variety of heterobimetallic complexes of the type Pd/M (M = Mn (), Fe (), Co (), Ni (), Cu (), Zn ()).

Effect of Zolpidem in the Aftermath of Traumatic Brain Injury: An MEG Study.

In the past two decades, many studies have shown the paradoxical efficacy of zolpidem, a hypnotic used to induce sleep, in transiently alleviating various disorders of consciousness such as traumatic brain injury (TBI), dystonia, and Parkinson's disease. The mechanism of action of this effect of zolpidem is of great research interest. In this case study, we use magnetoencephalography (MEG) to investigate a fully conscious, ex-coma patient who suffered from neurological difficulties for a few years due to traumatic brain injury.

Supramolecular self-assembly of heterobimetallic complexes: a new N,P-based, selective heteroditopic ligand.

Pyrimidine-hydrazone and phosphole architectures have been combined to create a new heteroditopic ligand capable of forming heterobimetallic Zn/Pd, Pb/Pd and Cu/Pd complexes in high yielding stepwise or one pot reactions. The catalytic activity of these complexes in Heck coupling and Miyaura borylation reactions was investigated.

A review of the evidence of zolpidem efficacy in neurological disability after brain damage due to stroke, trauma and hypoxia: A justification of further clinical trials.

During 15 years, 23 clinical reports and 6 studies have demonstrated associations between sub-sedative doses of zolpidem and recoveries from brain damage due to strokes, trauma and hypoxia. Clinical findings include unexpected awakenings from vegetative states and regressions of stroke symptoms after dosing that disappear during elimination and reappear on repeat dosing. Initially single-photon emission computed tomography scans showed improved perfusion within, around and distant from infarctions.

Three dosimetry models of lipoma arborescens treated by 90Y synovectomy.

Purpose: Lipoma arborescens (LA) is a benign intra-articular lipomatous proliferation of the synovial membrane. This extremely rare condition has previously been treated by intra-articular (90)Y radiosynoviorthesis but dosimetry literature on this form of radionuclide therapy is nonexistent. The authors detail methodology for successful treatment of LA and provide for the first time estimates of radiation dosimetry.

Lipoma arborescens successfully treated with (90)Y synovectomy.

Lipoma arborescens (LA) in the knee is a benign intra-articular lipomatous proliferation of the synovial membrane, and data on treatment of LA by radionuclide therapy is sparse. We present a rare case of bilateral LA in the knees successfully treated with injection of Y-citrate colloid. We assessed the biodistribution of the radiopharmaceutical through the use of SPECT/CT imaging.

Disorders of consciousness and pharmaceuticals that act on oxygen based amino acid and monoamine neurotransmitter pathways of the brain.

Oxygen based neurotransmitters in the synapses of the brain are proposed to play an important role in the generation of consciousness. They include the amino acids glutamate and GABA which use Krebs cycle precursors for their synthesis, and the monoamines dopamine, noradrenalin, adrenalin and serotonin, which are derived from tyrosine and tryptophan. During ischemia after an acute brain injury, a GABA surge often initiates brain suppression.

Blood-brain barrier integrity in a zolpidem-responder patient.

A 27-year-old neurologically disabled but fully conscious male zolpidem-responder patient was investigated for blood brain barrier (BBB) dysfunction 5 years after a traumatic brain injury. A baseline single-photon emission computed tomography (SPECT) technetium-99m-labelled hexamethylpropylene amine oxime (99mTcHMPAO) brain scan was performed and the patient was administered 10 mg zolpidem daily. The patient was rescanned 2 weeks later when 99mTcHMPAO was injected 1 hour after zolpidem application.

Radioiodine retention on percutaneous endoscopic gastrostomy tubes.

An 80-year-old male with recurrent thyroid cancer and a percutaneous endoscopic gastrostomy (PEG) tube in situ was referred for radioiodine therapy and was administered 5510 MBq I-131 sodium iodide intravenously. Sequential whole-body images taken over the subsequent 7 days for dosimetric evaluation revealed an area of persistent high uptake in the abdomen. Delayed imaging with single photon emission CT/CT at 15 days post administration revealed this uptake to be at the junction of the PEG tube with the anatomically normal stomach wall.

Neurotransmitters in disorders of consciousness and brain damage.

Restorations from disorders of consciousness such as the minimally conscious state and the vegetative state have been achieved spontaneously or by pharmacological agents such as zolpidem, baclofen, dopaminergic agents and tricyclic antidepressants in some patients. Other restoration methods have included electric and magnetic nerve stimulation, oxygen, Kreb's cycle constituent substitution and axonal re-growth. Although apparently unrelated, these methods all influence neurotransmitter availability or production within the brain.

Dissociation of Tc-99m DTPA in a nebulizer.

An unexpected biodistribution of nebulized Tc-99m diethylene triamine pentaacetic acid was detected after the ventilation of a patient referred for diagnosis of pulmonary embolism. Radiochemical purity testing of the stock vial showed more than 95% labelling. Further investigation indicated that the problem was possibly associated with a cleaning agent used for the nebulizer, leading to the dissociation of the Tc-99m diethylene triamine pentaacetic acid.

Clinical and brain SPECT scan response to zolpidem in patients after brain damage.

Unlabelled: Previous reports document transient improvements after daily zolpidem (CAS 82626-48-0) in patients with brain damage. This multi-patient study evaluates the response to zolpidem in neurologically disabled patients, using 99mTcHMPAO brain SPECT scans and clinical rating scales.

Method: 23 of 41 consecutive adult patients, at least 6 months after brain damage were identified as neurologically disabled patients by scoring less than 100/100 on the Barthel Index.

Orbital metastases from neuroendocrine carcinoma, masquerading as graves orbitopathy.

We describe a patient with metastases from neuroendocrine carcinoma masquerading as Graves ophthalmopathy. This rare tumour possibly has a propensity for orbital spread, and we postulate a mechanism evoking the 'seed and soil' hypothesis.

Neurotransmitters in coma, vegetative and minimally conscious states, pharmacological interventions.

Articles on pharmacological interventions in disorders of consciousness after brain damage are increasingly appearing in the medical literature. This hypothesis links disorders of consciousness to the depletion of oxygen reliant neurotransmitters based in two biochemical axes, the amino acid axis (glutamate/GABA) and the monoamine axis (dopamine/noradrenalin and serotonin). After a brain injury, an immediate response inside the brain constitutes a surge of amino acids such as glutamate, GABA and others.

GABA(A) alpha-1 subunit mediated desynchronization of elevated low frequency oscillations alleviates specific dysfunction in stroke--a case report.

Objective: The paradoxical effects of the hypnotic imidazopyridine zolpidem, widely reported in persistent vegetative state, have been replicated recently in brain-injured and cognitively impaired patients. However, the neuronal mechanisms underlying these benefits are yet to be demonstrated. We implemented contemporary neuroimaging methods to investigate sensorimotor and cognitive improvements, observed in stroke patient JP following zolpidem administration.

Drug induced arousal from the permanent vegetative state.

Background: Zolpidem is an omega 1 specific indirect GABA agonist that is used for insomnia, but may have efficacy in brain damage. The long term efficacy of zolpidem in the permanent vegetative state is described in three patients.

Method: Two motor vehicle accident patients and one near drowning patient, all of them in the permanent vegetative state for at least three years, were rated according to the Glasgow Coma and Rancho Los Amigos scale before and after zolpidem application.

Targeting the alpha-folate receptor with cyclopenta[g]quinazoline-based inhibitors of thymidylate synthase.

The alpha-FR has been reported to be overexpressed in many carcinomas, in particular those of the ovary and uterus. The high expression of alpha-FR in some tumours compared with normal tissues has been exploited over the last decade for folate-mediated targeting of macromolecules, anticancer drugs, imaging agents and nucleic acids to cancer cells. CB300638, a cyclopenta[g]quinazoline-based inhibitor of thymidylate synthase (TS), has been reported to have high affinity for the receptor and selectivity for alpha-FR overexpressing tumour cell lines.

Comparison of different methods of DatSCAN quantification.

Background: The quantification of DaTSCAN images can be used as an adjunct to visual assessment to differentiate between Parkinson's syndrome and essential tremor. Many programs have been written to assess the relative uptake in the striatum.

Aim: To compare two of the commercially available programs: QuantiSPECT, which analyses isolated data in two dimensions, and BRASS, which performs three-dimensional processing referencing a normal image template.

The influence of weather and environment on pulmonary embolism: pollutants and fossil fuels.

Previous publications have highlighted seasonal variations in the incidence of thrombosis and pulmonary embolism, and that weather patterns can influence these. While medical risk factors for pulmonary thrombo-embolism such as age, obesity, hypercoagulable states, cancer, previous thrombo-embolism, immobility, limb paralysis, surgery, major illness, trauma, hypotension, tachypnoea and right ventricular hypokinesis are not directly implicated regarding environmental factors such as weather, they could be influenced indirectly by these. This would be especially relevant in polluted areas that are associated with a higher pulmonary embolism risk.

Effect of zolpidem on brain injury and diaschisis as detected by 99mTc HMPAO brain SPECT in humans.

The study investigates the effect of zolpidem (CAS 82626-48-0) on brain injuries and cerebellar diaschisis. Four patients with varied brain injuries, three of them with cerebellar diaschisis, were imaged by 99mTc HMPAO Brain SPECT before and after application of zolpidem. The baseline SPECT before zolpidem showed poor tracer uptake in brain injury areas and cerebellar diaschisis.

Antifolate chemistry: synthesis of 4-[N-[(6RS)-2-methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino]benzoic acid via a (propargyl)Co2(CO)6+ complex.

A new route to compound 3 (4-[N-(6RS)-2-methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino]benzoic acid), a crucial intermediate for the synthesis of potent inhibitors of thymidylate synthase (TS), is described. In this sequence the C6-N10 bond was constructed first, by the reductive amination of 5-acetamido-6-bromoindan-1-one 6 with tert-butyl 4-aminobenzoate, then the cyclopenta[g]quinazolinone ring was formed and the propargyl group was introduced on the N10-position using the (propargyl)Co2(CO)6+ complex as the electrophilic propargyl reagent.