Plocamenols A-C, novel linear polyhalohydroxylated monoterpenes from Plocamium cartilagineum

Three new minor linear polyhalohydroxylated marine monoterpenes, plocamenols A-C (1-3), have been isolated from the red alga Plocamium cartilagineum. The structure and relative stereochemistry of these compounds were determined on the basis of spectroscopic evidence.     

Mitochondrial dysfunction associated with a mutation in the Notch3 gene in a CADASIL family

BACKGROUND: Cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by recurrent subcortical ischemic strokes and dementia caused by mutations in the Notch3 gene. In Drosophila melanogaster, Notch signaling has a pleiotropic effect, affecting most tissues of the organism during development. OBJECTIVE: To characterize a potential mitochondrial dysfunction associated with mutations in the Notch3 gene. METHODS: Biochemical, histochemical, molecular, and genetic analyses were performed on muscle biopsy specimens and fibroblasts obtained from patients of a Spanish family with CADASIL. Additional biochemical and molecular analyses of the N(55e11) mutant of D. melanogaster were performed. RESULTS: In muscle biopsy specimens, a significant decrease was found in the activity of complex I (NADH [reduced form of nicotinamide adenine dinucleotide] dehydrogenase), and in one patient, histochemical analysis showed the presence of ragged-red fibers with abnormal cytochrome c oxidase staining. Reduced fibroblast activity of complex V (ATP synthase) was found. Supporting data on patients with CADASIL, it was found that the mutation N(55e11) in Drosophila decreases the activity of mitochondrial respiratory complexes I and V. CONCLUSIONS: Mitochondrial respiratory chain activity responds, directly or indirectly, to the Notch signaling pathway. Mitochondrial dysfunction in patients with CADASIL may be an epiphenomenon, but results of this study suggest that the pathophysiology of the disease could include a defect in oxidative phosphorylation.     

Integration of inpatient and outpatient services in an acute care transplant unit

Creating an ambulatory outpatient service for transplant recipients in an inpatient care unit allows several goals to be met: decreased inpatient length of stay, decreased cost per case, and increased patient satisfaction. By using 6 inpatient beds for ambulatory outpatient procedures, the leadership staff of an adult inpatient care unit in Mount Sinai Medical Center consolidated adult transplant services into a single area promoting quality transplant care.     

Anxiogenic-like activity of L-655,708, a selective ligand for the benzodiazepine site of GABA(A) receptors which contain the alpha-5 subunit,in the elevated plus-maze test

GABA_A receptor is a transmembrane hetero-oligomeric protein which consists of five subunits, the combination of which confers unique pharmacological properties to the receptor. L-655,708 is a new ligand selective for GABA_A receptors containing an alpha-5 subunit. It is a partial inverse agonist that exhibits a 100-fold higher affinity for alpha-5 containing receptors, compared with alpha-1 containing receptors. The aim of this study was to examine the effects of L-655,708 (0.625–5 mg/kg ip) on anxiety tested in the elevated plus-maze in male mice. A number of classical parameters were collected: (a) Open arm duration; (b) Closed arm duration; (c) Central platform duration; (d) Open arm frequency; (e) Closed arm frequency; and (f) Total number of entries in the arms. Likewise, different ethological measures were also obtained (rears, head-dipping [HD], stretched attend posture [SAP] and grooming). Mice treated with L-655,708 showed a marked increase in the frequency of entries and the time spent in closed arms, as well as a reduction in the frequency of entries and the time spent in open arms, as compared with the control group. Unprotected HDs were also significantly decreased after treatment with the drug. Overall, these results indicate that L-655,708 could exhibit an anxiogenic-like profile in the elevated plus-maze test. This ligand is selective for GABA_A receptors containing an alpha-5 subunit, which is mainly expressed over the hippocampal formation, a region which has been involved in the modulation of anxiety.     

Analysis of the human fetal skeleton and organs with xeroradiography

We have used xeroradiography to study normal and abnormal fetuses including some with anencephaly, hydrocephalus, spina bifida, osteogenesis imperfecta (type IV), Jeune syndrome, radial aplasia, thanatophoric dysplasia, and Pena-Shokeir syndrome. Xeroradiography images the lines of ossification and epiphyses in great detail, shows ossification, and reveals abnormalities that alter bone modeling as seen in Jeune syndrome, osteogenesis imperfecta (type IV), and thanatophoric dysplasia. This technique can be used successfully to examine soft tissues and organs. It can also be used in combination with contrast materials to identify the lateral ventricles, the cardiovascular, gastrointestinal, urinary, and respiratory systems, and the cavities (pleural and peritoneal) of the fetal body.     

Subcortical arteriosclerotic encephalopathy (Binswanger's disease): a report of five patients

Five patients with variable clinical symptoms were diagnosed as having--subcortical arteriosclerotic encephalopathy (Binswanger disease) based on the presence of lacunar infarcts in basal ganglia, various abnormalities of subcortical white matter and severe thickening and hyalinization of penetrating arteries and arterioles. One case had a classical clinical picture while in the others the course of the disease was short and was associated with severe systemic abnormalities. The variability of the clinical features, the identify of "classical" clinical symptoms with other forms of cerebral arteriosclerosis, the similarity between "atypical" cases and other entities, and the high frequency of associated conditions makes it difficult to characterize the clinical pathological entity called subcortical arteriosclerotic encephalopathy.     

Restraint-induced stress ulcer. I. Hypothalamic,urinary, and adrenal biochemical studies

The purpose of these experiments was to study the incidence of stress ulcers in restrained rats and to correlate it with hypothalamic and adrenal cortical and medullary activity, with and without vagotomy. A total of 217 adult rats were used, grouped into 56 sets, and distributed at random in 5 experimental groups. Restraint was followed by a 79% incidence of ulceration in the glandular portion of the gastric mucosa. Vagotomy made these worse (p<0.01). Hypothalamic levels of catecholamines and serotonin showed no significant changes. Urinary measurements revealed decreased excretion of 17-ketosteroids (p<0.001), increased excretion of uropepsinogen (p<0.01), and no significant changes in vanillylmandelic acid among the rats submitted to immobilization. In the adrenal glands of stressed animals, there was a decreased level of catecholamines (p<0.01) and no significant changes in corticosteroid content (17-ketosteroids). These results suggest that hypothalamic stimulation and the participation of the adrenal glands are not essential factors in the pathogenesis of restraint-induced experimental stress ulcer.     

Multiple intracranial arterial occlusions (moyamoya disease) in patients with neurofibromatosis one case report with autopsy

Summary The authors report two cases of multiple intracranial arterial occlusive disease occurring in patients affected by neurofibromatosis. Clinicoradiological presentation was, in both cases, typical of the so-called Moyamoya disease. Special emphasis on the anatomopathological necropsy findings in the second case is made, because, to the authors' knowledge, this is the first reported case in the literature.     

Strategies for design of non peptide CCK1R agonist/antagonist ligands

This review mainly covers last five year literature on CCK1R agonists and antagonists. These CCK1R ligands have been found following the two usual and complementary strategies for drug discovery: rational design based on structure activity relationships on the CCK-7 and CCK-4 peptide sequences of the endogenous ligands and random screening of diverse compounds, followed by hit optimization. The first group includes: chimeric bifunctional opioid/CCK peptides, designed as opioid agonists with balanced CCK1R/CCK2R antagonist activity for the treatment of neuropathic pain, antagonist and agonist dipeptoids, and 1,3-dioxoperhydropyrido[1,2-c]pyrimidine- and anthranilic acid-based antagonists. Among the ligands derived from random screening, a few new 1,4-benzodiazepine-, 1,5-benzodiazepine-, and five member ring heterocycle-based CCK1R ligands have been reported. Finally, taking into account the importance of receptor mapping studies for ligand optimization and future precise de novo receptor structure-based design of new selective and more effective ligands, the most significant conclusions of these studies have also been reviewed.