Infantile spasms in Down syndrome: a report of 5 cases and review of the literature.

Five patients with Down syndrome (DS) and infantile spasms were examined in a four-year interval. Previous reports of this association have been infrequent except during experimental treatment with 5-hydroxytryptophan, a precursor of serotonin. Malformations of the brain in DS are associated with an increased incidence of epilepsy, and both gross and cytoarchitectural anomalies have been described. The severity and distribution of these central nervous system anomalies presumably predispose to the infantile spasms. The contribution of altered serotonin metabolism is uncertain.     

Salt-dependent conformational diversity of alternating poly (Glu-Leu)

Alternating poly(Glu-Leu) was synthesized by the condensation of the corresponding dipeptide p-nitrophenyl ester at high concentration. It exhibits a random coil structure in pure water at neutral pH. Addition of monovalent cations, such as NH⁺₄ to a final 0.1 M solution, induces a transition to a water soluble β-structure. The salt effect is quite selective since no transition was observed with Li⁺, Na⁺ or Cs⁺ ions. Addition of 0.5 equiv. of calcium, cobalt or manganese chlorides per glutamyl residue induces similar coil to β-sheet transitions. No polymer precipitation was observed at these very low salt concentrations. Addition of 0.5 equiv. of Cu²⁺ or 0.15 equiv. of Fe³⁺ induces a coil to α-helix transition. Molecular modeling has been used to understand tentatively the main factors controlling the different conformations observed with the various metal ions. © Munksgaard 1997.     

Availability of micronutrients from dried, encapsulated fruit and vegetable preparations: a study in healthy volunteers

Background High levels of consumption of fruit and vegetables, which contain antioxidant nutrients including vitamins C and E as well as β‐carotene, are associated with reduced rates of atherosclerotic arterial disease and some cancers. Low plasma levels of these micronutrients are associated with an increased risk of chronic degenerative disease. While increasing consumption of fruit and vegetables would be desirable, many factors including cost tend to prevent this. Preparations of the active components of fruit and vegetables encapsulated to achieve convenience may contribute to solving this problem. Aims This study was designed to determine whether two such supplements prepared from dehydrated fruit and vegetable extracts (Juice Plus+? Fruit and Juice Plus+? Vegetable) would result in elevation in blood concentrations of antioxidants to levels associated with lower disease risk. Methods Sixteen healthy subjects (eight male, eight female, aged 18–52 years) were screened to exclude disease and to exclude any individual with a serum β‐carotene below 0.05 µmol L^–1, and were divided into two groups of eight, each to consume either the fruit or vegetable preparation. Four days before administration of the capsules the subjects commenced a low β‐carotene diet. Venous blood samples for determination of vitamin C, vitamin E (as α‐tocopherol) and β‐carotene were taken in the morning on days 0, 2, 4, 6 and 7, after a 10‐h fast. Two capsules of either the fruit preparation (containing vitamin E 30 mg, vitamin C 150 mg and β‐carotene 6 mg) or vegetable preparation (containing vitamin E 30 mg, vitamin C 50 mg and β‐carotene 9 mg) were taken on days 0–6 inclusive with a 610‐kcal breakfast (47% energy from fat). Results Serum β‐carotene levels rose significantly by 0.56 µmol L^–1 and 0.54 µmol L^–1 after fruit and vegetable preparations, respectively, by day 7, vitamin E levels rose significantly by 3.1 µmol L^–1 after the fruit preparation but not after the vegetable preparation and vitamin C rose significantly from 28 to 62 µmol L^–1, and from 32 to 50 µmol L^–1 after the fruit and vegetable preparations, respectively. Plasma malondialdehyde, regarded as a general indicator of peroxidation, fell significantly by 19 × 10^–5 µmol L^–1 (about a 40% reduction) in both treatment groups. Conclusions These results indicate that concentrated extracts of fruits and vegetables can raise blood antioxidant levels into the ranges associated with reduced risk of disease and that this reduces the concentration of a general measure of lipid peroxidation. Further studies, especially in those with disease characterized by increased oxidative stress, are indicated.     

Neuroprotective actions of lithium]

Lithium has long been one of the primary drugs used to treat bipolar mood disorder. However, neither the etiology of this disease nor the therapeutic mechanism(s) of this drug is well understood. Several lines of clinical evidence suggest that lithium has neurotrophic actions. For example chronic lithium treatment increases the volume of gray matter and the content of N-acetyl-aspartate, a cell survival marker, in bipolar mood disorder patients (Moore et al., 2000). Moreover, treatment with this mood-stabilizer suppresses the decrease in the volume of the subgenual pre-frontal cortex found in bipolar patients (Drevets, 2001). To elucidate molecular mechanisms underlying the neuroprotective and neurotrophic actions of lithium, we employed a preparation of cultured cortical neurons prepared form embryonic rats. We found that treatment with therapeutic doses (0.2-1.2 mM) of lithium robustly protects cortical neurons from multiple insults, notably glutamate-induced excitotoxicity. The neuroprotection against glutamate excitotoxicity is time-dependent, requiring treatment for 5-6 days for maximal effect, and is associated with a reduction in NMDA receptor-mediated Ca2+ influx. The latter is correlated with a decrease in Tyrosine 1472 phosphorylation levels in the NR2B subunit of NMDA receptors and a loss of Src kinase activity which is involved in NR2B tyrosine phosphorylation. Neither the activity of total tyrosine protein kinase nor that of tyrosine protein phosphatase is affected by this drug, indicating the selectivity of the modulation. Lithium neuroprotection against excitotoxicity is inhibited by a BDNF-neutralizing antibody and K252a, a Trk antagonist. Lithium treatment time-dependently increases the intracellular level of BDNF in cortical neurons and activates its receptor, TrkB. The neuroprotection can be completely blocked by either heterozygous or homozygous knockout of the BDNF gene. These results suggest a central role of BDNF and TrkB in mediating the neuroprotective effects of this mood-stabilizer. Finally, long-term lithium treatment of cortical neurons stimulates the proliferation of their progenitor cells detected by co-labeling with BrdU and nestin. Lithium pretreatment also blocks the decrease in progenitor proliferation induced by glutamate, glucocorticoids and haloperidol, suggesting a role in CNS neuroplasticity. We used animal models to investigate further therapeutic potentials for lithium. In the MCAO/reperfusion model of stroke, we found that post-insult treatment with lithium robustly reduced infarct volume and neurological deficits. These beneficial effects were evident when therapeutic concentrations of lithium were injected at least up to 3 h after ischemic onset. The neuroprotection was associated with activation of heat-shock factor-1 and induction of heat-shock protein-70, a cytoprotective protein. In a rat excitotoxic model of Huntington's disease, the excitotoxin-induced loss of striatal medium-sized neurons was markedly reduced by lithium. This lithium protection was correlated with up-regulation of cytoprotective Bcl-2 and down-regulation of apoptotic proteins p53 and Bax, and neurons showing DNA damage and caspase-3 activation. Taken together, our results provide a new insight into the molecular mechanisms involved in lithium neuroprotection against glutamate excitotoxicity. Moreover, these novel molecular and cellular actions might contribute to the neurotrophic and neuroprotective actions of this mood-stabilizer in patients, and could be related to its clinical efficacy for treating mood disorder patients. Clearly, mood-stabilizers may have expanded use for treating excitotoxin-related neurodegenerative diseases.     

Glioblastoma of the cerebellum. Computed tomographic and pathologic considerations

Cerebellar glioblastoma is a brain malignancy that is often difficult to distinguish from metastatic disease in the elderly before biopsy. The clinical course and computed tomographic appearance of four patients with multiform glioblastoma of the cerebellum are presented and correlated with other reports in the literature. The appearance of a cerebellar hemispheric lesion with little mass effect is described, and the pathology of the tumor is reviewed.     

Gingival and mucosal reactions after intensive chlorhexidine gel treatment with or without oral hygiene measures

Abstract – The aim of this study was to elucidate whether soft tissue reactions during chlorhexidine (CHX) treatment might be associated with meticulous oral hygiene measures. A commercially available 1% chlorhexidine digluconate gel (Hibitane Dental Gel) was applied in a custom tray for the mandibular arch, 10 min daily, for 14 days. A split mouth approach was used to allow evaluation of the effect of oral hygiene measures with toothbrush, toothpaste, and dental floss on one side of the arch. During the treatment period, 8 out of 12 subjects developed gingival and/or mucosal reactions appearing as white patches or ulcerations. Both the gingival reactions on the buccal marginal gingiva and the mucosal reactions near the margin of the custom tray occurred only when the gel treatment was combined with meticulous oral hygiene measures. The white patches, which could easily be detached, leaving ulcerated areas, consisted entirely of stratified squamous epithelium. The findings suggest that intensive treatment with chlorhexidine gel, in individually fitted custom trays, combined with meticulous oral hygiene measures may induce toxic effects on the surface layers of the gingiva and mucosa.     

CT in the early diagnosis of herpes simplex encephalitis

Herpes simplex is the most common cause of sporadic viral encephalitis. The recent development of specific antiviral chemotherapeutic agents offers new optimism for patients with this disorder if therapy is begun on or before the fifth day of the disease. Eight patients with herpes simplex encephalitis were studied by CT, and a characteristic but not pathognomonic pattern was observed. In each case a low density lesion was noted in the medial portion of the temporal lobe with extension into the Island of Reil. Sparing of the lenticular nucleus was observed in all cases. Mass effect and streaky linear enhancement after contrast administration was also seen. Unfortunately, the findings may be subtle or absent before the fifth day of disease, and thus CT scans must be examined with a high index of suspicion if the correct diagnosis is to be made at a time when therapy may prove useful. Hemorrhagic areas are rarely observed on CT in this disorder despite the frequent occurrence on pathologic studies. The full extent of involvement may not be appreciated on scans obtained during the first 10 days of the disease.