Postnatal emergence of mature release properties in terminals of rat fast- and slow-twitch muscles

Motor nerve terminals in adult mammalian slow-twitch muscles have lower levels of spontaneous and evoked neurotransmitter release than terminals in fast-twitch muscles. These reflect adaptive differences, allowing terminals in slow (postural) muscles to sustain release during the prolonged firing trains experienced in vivo. Here we ask whether these differences in terminal release properties in Sprague-Dawley rat extensor digitorum longus (EDL, fast) and soleus (slow) muscles reflect their early cytodifferentiation in the embryo or whether they might be adaptations to their distinct mature activity patterns, which emerge around two weeks postnatally. We find that the mature pattern of differences in release arise through co-ordinated increases in presynaptically dependent release properties (quantal content, spontaneous release frequency and evoked potential amplitude), beginning at three weeks, which are particularly substantial in EDL. In contrast, other synaptic properties are either consistently greater in the same muscle throughout development (evoked potential kinetics, muscle fibre diameter) or display no systematic muscle type-dependent differences (terminal area, input resistance, spontaneous release amplitude). Thus, the emergence of adaptive differences in terminal release properties correlates with the differentiation of locomotor activity patterns in postnatal rat hindlimb muscles.     

Clinical, electrophysiological and neuropsychological findings of twenty-two children with mesial temporal sclerosis

Twenty-two patients, followed with the diagnosis of epilepsy between the ages of 8.5 and 19 years who were found to have mesial temporal sclerosis (MTS) on brain magnetic resonance imaging (MRI) were evaluated according to their clinical, electrophysiological and neuropsychological characteristics, and assessed for the significance of neuropsychological tests on lateralization. In both MTS groups, a remarkable number of patients had their intial seizure before one year of age (45.5% in the right MTS group, and 36.4% in the left MTS group). Half of the patients were seizure-free for a period of two months-9.5 years (average 3.9 years). The duration between the febrile seizure and first non-febrile seizure was 6.2 years. Eleven patients had MTS on the left temporal lobe. Interictal EEG was normal in five (22.5%) patients; 10 (45.5%) had temporal spike on the corresponding side with MTS. Six (27.3%) patients had paroxysmal activity and voltage asymmetry on cortical areas other than temporal region. The Wechsler Memory Scale (WMS), Visual Reproduction Subtest and Auditory Verbal Learning Test (AVLT) Delayed Recall and Retrieval Subtest performances were poor in the right MTS group.     

A method for off-line nasal nitric oxide measurement

We conducted a study to test the accuracy of an immediate and delayed off-line technique for measuring nasal nitric oxide (NO) by comparing it with on-line measurements. With the assistance of one volunteer, we obtained these measurements during 30 sessions over a period of 2 months. Off-line measurements were made immediately following the acquisition of NO samples and 1, 2, and 4 hours later. NO samples were obtained from nasal air collected in syringes. We found that the correlation between on-line measurements and the immediate and delayed off-line measurements ranged from 95 to 98%, according to a Bland-Altman analysis. We conclude that off-line nasal NO measurements can be reliably used in clinical practice and research projects, thus obviating the need for patients/subjects to be in close proximity to the analyzer. Off-line nasal NO measurements can effectively substitute for on-line measurements when the latter technique is not practical.     

High output heart failure 8 months after an acquired arteriovenous fistula

Congestive heart failure (CHF) due to hyperkinetic states can occur in systemic diseases and in arteriovenous fistulas. An 18 year old Turkish male patient complaining of dyspnea and palpitations, who had suffered a stab wound to his abdomen eight months earlier, was admitted to our clinic. Auscultation revealed a systolodiastolic murmur over the entire abdomen. Chest x-rays demonstrated significant cardiomegaly. Echocardiography revealed biatrial enlargement and significant mitral and tricuspid regurgitation accompanied by dilatation of the inferior vena cava. Right heart catheterization showed increased oxygen saturation at the inferior vena cava. A diagnosis of an aortocaval fistula was made by aortography. The symptoms subsided and valvular regurgitations ceased alter surgical correction. This rare case demonstrates the significance of routine physical examination and history of the patient.     

Elevated levels of phosphorylated neurofilament proteins in cerebrospinal fluid of Alzheimer disease patients

Neurofilament (NF) subunits NF-H, NF-M and NF-L are hyperphosphorylated and elevated in Alzheimer disease (AD) brain. We investigated the level and phosphorylation states of NF subunits in lumbar cerebrospinal fluid (CSF) from living patients by bienzyme substrate-recycle enzyme-linked immunosorbent assay. We found: (i), that the levels of phosphorylated NF-H/M (pNF-H/M), non-phosphorylated NF-H/M (npNF-H/M) and NF-L were significantly higher (pNF-H/M, 12–24-fold; npNF-H/M, 3–4-fold) in neurologically healthy aged people than young control individuals; (ii), that in AD, the levels of npNF-H/M, and NF-L were similar to vascular dementia (VaD), and higher than in age-matched controls; and (iii), that the levels of pNF-H/M were significantly higher than in aged controls, non-AD neurological disorders and VaD. Based on these findings, it is suggested that the increased level of total NF proteins in CSF could be used as a marker for brain aging and neurodegenerative disorders in general, and the levels of pNF-H/M as a marker to discriminate AD from normal brain aging and as well as neurological conditions including VaD.     

Evaluation of the outcomes of short bowel syndrome and indications for intestinal transplantation

Long-term parenteral nutrition (PN) and intestinal transplantation (IT) are life-saving therapies for patients with short bowel syndrome (SBS). However, indications and timing of these therapies are controversial. In this study we aimed to evaluate the indications for IT. Forty-two patients, each with <100 cm of small bowel, were divided into three groups according to the length of remnant: group I patients (n = 18): colon plus 50 to 100 cm of small bowel (SB); group II patients (n = 14): colon plus <50 cm of SB; and group III patients (n = 10): <50 cm of SB without colon. One-year mortality rates for groups I, II, and III were 50%, 72%, and 100%, respectively. All group I survivors developed intestinal adaptation, returning to regular oral feedings at 1 year. Interestingly, three of four surviving patients in group II developed adaptation and were fed an oral short bowel diet (SBD) at 1 year. None of the group III patients survived >1 year, dying due to multiorgan failure in the early postoperative period or from sepsis within 1 year. We conclude that patients with a very short bowel are candidates for IT when stable. If the colon is intact, however, regardless of small bowel remnant length, the patient should be given a chance to develop intestinal adaptation before making the decision for permanent PN or IT.     

The effect of topical fluticasone on nasal nitric oxide levels in a patient with allergic rhinitis

Nitric oxide (NO) in exhaled breath is produced primarily by the upper respiratory airway mucosa. The nasal output of this gas is increased in patients with allergic rhinitis. We performed a study on a 41-year-old nonsmoking male volunteer with allergic rhinitis to investigate the effect of fluticasone nasal spray on nasal NO output (VNO). A total of 28 nasal NO measurements from both nostrils were taken during the 2-month period of June and July 2002. During the second half of the study period (treatment phase), the patient took fluticasone in doses of 100 micrograms per nostril once a day. During the treatment phase, nasal NO measurements were taken 10 days after the initiation of treatment. In addition, we also recorded the patient's nasal symptom scores and the grass pollen counts in the greater Pittsburgh area. The patient's mean VNO was 989.9 nl/min prior to treatment and 787.7 nl/min following treatment--a statistically significant 20.4% decrease (p < 0.01). The findings of our study support the observation that topical nasal steroid treatment decreases NO production in sinonasal mucosa.     

The Development of β-Lactam Antibiotics in Response to the Evolution of β-Lactamases

beta-Lactam antibiotics, viz., penicillin, penicillin derivatives, cephalosporins, cephamycins, carbapenems, monobactams. and monocarbams, are the most widely used of all antimicrobial classes by virtue of their high efficacy and specificity and the availability of several derivatives. The expression of one or several beta-lactamases (beta-lactam antibiotic-inactivating enzymes) represents the most widespread and the most clinically relevant resistance mechanism to these antibiotics. The development of beta-lactam antibiotics has thus been a continuous battle of the design of new compounds to withstand inactivation by the ever-increasing diversity of beta-lactamases. This article traces antibiotic development in response to the evolution of beta-lactamases.     

A study on the genotoxic activities of some new benzoxazoles

The Bacillus subtilis rec assay has been specially developed to detect DNA-damaging potential in chemicals, with the rationale based on the relative difference of survival of a DNA repair combination proficient strains and its deficient strain, which is interpreted as genotoxicity. The genotoxic activities of newly (1–6) and previously (7–18) synthesized various benzoxazoles and benzimidazoles were analyzed via the B. subtilis rec assay. Newly obtained benzoxazole and benzimidazole derivatives (1–6) were synthesized in the presence of polyphosphoric acid (PPA) and 6 N HCl, respectively to detect their DNA-damaging activities. Among the tested compounds, 6-methyl-2-(o-chlorophenyl)benzoxazole (9), 5-amino-2-(p-methylbenzyl)benzoxazole (4), 5-(p-fluorobenzamido)-2-phenylbenzoxazole (13), and 2-(p-methylaminophenyl)benzoxazole (18) showed genotoxic activities having Rec₅₀ values of 1.85, 1.74, 1.60, and 1.50 or S-probit values of 0.534, 0.482, 0.460, and 0.357, respectively. On the other hand, 2-(p-bromobenzyl)-5-methylbenzimidazole (6) and 2-benzyl-5-(p-fluorophenylacetamido)-benzoxazole (15) were exhibited a reverse effect that displayed a bacterial growth in the rec ^- strains while there was no any bacterial growth in rec ⁺ strains at the same concentration.