Severe congenital absence of skin in a preterm infant

A severe case of aplasia cutis congenita in a preterm infant is described. Although major problems with thermoregulation and fluid balance were anticipated, these parameters were relatively easy to control once the patient was stabilized. Meticulous skin care and rapid formation of a membranous-like fibrous tissue layer covering the denuded areas probably played an important role in minimizing excessive fluid and heat loss. The prognosis in aplasia cutis congenita is determined by the underlying associated anomalies, the severity of skin lesions and, in our case, the maturity of the infant who died from complications of prematurity.     

The IGF-I amino-terminal tripeptide glycine-proline-glutamate (GPE) is neuroprotective to striatum in the quinolinic acid lesion animal model of Huntington's disease.

Huntington's disease is an incurable genetic neurological disorder characterized by the relatively selective degeneration of the striatum. Lesioning of the striatum in rodents using the excitatory amino acid agonist, quinolinic acid (QA), effectively mimics the human neuropathology seen in Huntington's disease. Using this animal model of Huntington's disease, we investigated the ability of the insulin-like growth factor-I (IGF-I) amino-terminal tripeptide glycine-proline-glutamate (GPE) to protect striatal neurons from degeneration. Adult rats received a single unilateral intrastriatal injection of QA (100 nmol) and then daily injection of either vehicle or GPE (0.3 microgram/microliter/day) into the striatum for 7 days. QA at this dose resulted in a partial lesioning of the striatum after 7 days to approximately 50% of cells of unlesioned levels in vehicle-treated animals. The major striatal neuronal phenotype, GABAergic projection neurons, were identified by immunocytochemical labeling of either glutamate decarboxylase 67 (GAD(67)) or the calcium binding protein calbindin in alternate sections. Treatment with GPE for 7 days reversed the loss in projection neurons when assessed by counts of calbindin-stained cells; however, these rescued cells did not regain immunologically detectable levels of GAD(67). GPE also significantly reversed the phenotypic degeneration of cholinergic interneurons identified by immunolabeling for choline acetyltransferase (ChAT) and NADPH diaphorase interneurons identified histochemically. GPE treatment failed to rescue the calcium binding protein interneuron populations of parvalbumin and calretinin neurons. These findings reveal that exogenous administration of GPE selectively prevents excitotoxin induced phenotypic degeneration of striatal projection neurons and cholinergic and NADPH diaphorase interneurons in an animal model of Huntington's disease.     

GABAA receptors in the primate basal ganglia: An autoradiographic and a light and electron microscopic immunohistochemical study of the α1 and β2,3 subunits in the baboon brain

The distribution of gamma-aminobutyric acid_A (GABA_A) receptors was investigated in the basal ganglia in the baboon brain by using receptor autoradiography and the immunohistochemical localisation of the α₁ and β_2,3 subunits of the GABA_A receptor by light and electron microscopy. In the caudate-putamen, the α₁ subunit was distributed in high densities in the matrix compartment, and the β_2,3 subunits were more homogeneously distributed; the globus pallidus showed lower levels of the α₁ and β_2,3 subunits. Four types of α₁ subunit immunoreactive neurons were identified in the baboon striatum: the most numerous (75%) were type 1 medium-sized aspiny neurons; type 2 (2%) were large aspiny neurons with an indented nuclear membrane located in the ventral striatum; type 3 neurons were the least numerous (1%) and were comprised of large neurons in the ventromedial regions of the striatum; and type 4 (22%) neurons were medium to large aspiny neurons located in striosomes. At the ultrastructural level, α₁ and β_2,3 subunit immunoreactivity was localised in the neuropil of the striatum in both symmetrical and asymmetrical synaptic contacts. In the globus pallidus, α₁ and β_2,3 subunits were localised on large neurons and were found in three types of synaptic terminals: type 1 terminals were small and established symmetrical synapses; type 2 terminals were large; and type 3 terminals formed small synaptic terminals with subjunctional dense bodies. These results show that the subunit composition of GABA_A receptors varies between the striosome and the matrix compartments in the striatum and that there is receptor subunit homogeneity in the globus pallidus. J. Comp. Neurol. 397:297–325, 1998. © 1998 Wiley-Liss, Inc.     

Dramatic Improvement in Decompensated Right Heart Failure due to Severe Tricuspid Regurgitation Following Ligation of Arteriovenous Fistula in a Renal Transplant Recipient

Arteriovenous (AV) fistulas with high blood flow rate are necessary for adequate hemodialysis, but they can also cause significant hemodynamic changes, including raised cardiac output, left ventricular hypertrophy and occasionally overt cardiac failure (Basile et al., Nephrol Dial Transplant, 23, 2008, 282; Unger et al., Am J Transplant, 4, 2004, 2038). We now report a case of rapid and dramatic improvement in symptomatic right heart failure due to severe tricuspid regurgitation following ligation of an arteriovenous fistula. Cardiac magnetic resonance imaging (MRI) performed before and after the ligation of fistula showed striking improvement in both the tricuspid regurgitation and right ventricular dimensions, with minimal impact on left ventricular mass, size, and function.     

Huntington’s disease mice and human brain tissue exhibit increased G3BP1 granules and TDP43 mislocalization

Chronic cellular stress associated with neurodegenerative disease can result in the persistence of stress granule (SG) structures, membraneless organelles that form in response to cellular stress. In Huntington’s disease (HD), chronic expression of mutant huntingtin generates various forms of cellular stress, including activation of the unfolded protein response and oxidative stress. However, it has yet to be determined whether SGs are a feature of HD neuropathology. We examined the miRNA composition of extracellular vesicles (EVs) present in the cerebrospinal fluid (CSF) of patients with HD and show that a subset of their target mRNAs were differentially expressed in the prefrontal cortex. Of these targets, SG components were enriched, including the SG-nucleating Ras GTPase-activating protein-binding protein 1 (G3BP1). We investigated localization and levels of G3BP1 and found a significant increase in the density of G3BP1-positive granules in the cortex and hippocampus of R6/2 transgenic mice and in the superior frontal cortex of the brains of patients with HD. Intriguingly, we also observed that the SG-associated TAR DNA-binding protein 43 (TDP43), a nuclear RNA/DNA binding protein, was mislocalized to the cytoplasm of G3BP1 granule–positive HD cortical neurons. These findings suggest that G3BP1 SG dynamics may play a role in the pathophysiology of HD.     

The QE Health Scale (QEHS): assessment of the clinical reliability and validity of a spiritually based holistic health measure

Purpose. To assess the clinical reliability and validity of a holistic health measure, the QE Health Scale (QEHS), for use with people with physical disabilities.

Method. A test-retest design saw the QEHS administered and compared with established measures of health at admission and discharge from three-week inpatient rehabilitation programmes. Data was analysed by factor and correlation analysis. Clinician-reported credibility and usefulness of the theoretical basis of the QEHS, the QEHS itself, and Patient Profiles derived from the QEHS were also used to evaluate clinical validity.

Results. The QEHS was judged to possess satisfactory reliability and validity.

Conclusion. The QEHS is a clinically reliable, valid, credible and useful holistic health instrument to facilitate client-centred therapeutic interventions, inform decision-making and evaluate outcomes for people with physical disabilities.     

Determination of tryptamine in rat brain by gas chromatography-mass spectrometry

Tryptamine (TA) occurs in trace levels in the brain, but its role in the central nervous system is not clear. However, there is evidence that TA may be a neuromodulator since it binds to specific binding sites in the brain. TA was measured as a diheptafluorobutyryl derivative in rat whole brain by capillary gas chromatography—mass spectrometry using negative chemical ionization (NCI) and single ion monitoring (SIM). d₄-TA was used as the internal standard. The ions m/z 532 and m/z 536 were monitored to identify TA and d₄-TA, respectively and to calculate the concentration of TA in rat whole brain which was found to be 0.19 ± 0.08 ng g⁻¹ (n = 8). The results confirm the earlier TA concentrations measured by GC—MS using positive electron impact ionization. However, NCI improved the signal/noise ratio of the method increasing its sensitivity for TA.     

1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives

A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.