Temporal Lobe Epileptogenesis and Epilepsy in the Developing Brain: Bridging the Gap Between the Laboratory and the Clinic. Progression, But in What Direction?

Summary:  The origins of human mesial temporal lobe epilepsy and hippocampal sclerosis are still not well understood. Hippocampal sclerosis and temporal lobe epileptogenesis involve a series of pathologies including hippocampal neuronal loss and gliosis, axonal reorganization, and maybe hippocampal neoneurogenesis. However, the causality of these events is unclear as well as their relation to the factors that may precipitate epileptogenesis. Significant differences between temporal lobe epileptogenesis in the adult and immature brain may require differential approaches. Hereditary factors also may participate in some cases of hippocampal sclerosis. The key point is to identify the significance of these age-dependent changes and to design preventive treatments. Novel strategies for the prevention and treatment of mesial temporal lobe epilepsy and hippocampal sclerosis may include rational use of neuroprotective agents, hormonotherapy, immunizations, and immunotherapy.     

Ultrastructure of a two-cell human embryo

Summary A two-cell human embryo recovered from the Fallopian tube 82 h following the LH peak in plasma and 37 h after a single episode of intercourse was examined by transmission electron microscopy. At the time of recovery the embryo was denuded of cumulus cells, and both the zona pellucida and the two adjoining blastomeres were intact. The finding of two polar bodies in the perivitelline space, two nucleated blastomeres and remnants of the fertilizing sperm tail within the cytoplasm of one of them, were considered as evidences that the embryo was normally fertilized. Among the most compicuous features found were the presence of very distinct desmosome-like structure between blastomeres, and the cytoplasmic cell organelles distribution in three areas referred as: a sub-cortical, a middle and a perinuclear bands. An outstanding feature was the extensive blebbing of the nuclear envelope. In general, the features seem to correspond to a normally developing two-cell embryo undergoing cleavage at a normal rate.     

用显微分光光度计对几种不同类型肺癌癌细胞DNA含量的初步观测

本文用显微分光光度计对39例手术切除的不同组织学类型的人体肺癌标本癌细胞核的DNA含量进行了测量。其中高、中、低分化的鳞癌分别为3、6和5例;高、中、低分化的腺癌分别为3、5和5例;未分化癌大细胞型和小细胞型各为3例和6例。结果发现各类型肺癌的DNA含量均有统计学上的差异(P<0.01)。各DNA含量直方图的峰值部位及分布范围亦不同。从而提示了根据DNA含量的不同,可能有助于肺癌组织学类型及其分化程度的判别:而DNA含量直方图对肺癌类型的判别亦可能是有益的。     

Non-nociceptive capsaicin-sensitive nerve terminal stimulation allows for an original vasodilatory reflex in the human skin

A significant increase of cutaneous laser Doppler flowmetry was found before blood flow decreases with increasing pressure during a 5 mmHg min⁻¹ increase of pressure strain on the finger. Pre-treatment with a local anaesthetic or chronically applied capsaicin, resulted in the disappearance of the vasodilatory response. These results suggest an original vasodilatory axon reflex response to non-noxious pressure strain which is initiated by capsaicin-sensitive nerve terminals in the human skin.     

Crossed inhibition of the soleus H reflex during passive pedalling movement

We hypothesized that sensory input from the moving leg induces presynaptic inhibition of the soleus H reflex pathway in the contralateral stationary leg. The results showed a crossed inhibition during passive pedalling movement of the leg, which was not removed by low levels of tonic contraction of soleus in the stationary leg. The inhibition was correlated exponentially to the rate of the movement (R²=0.934, P<0.05) and was not dependent on the quadrants through which the moving leg was passing. Static flexion of the stationary leg caused ipsilateral inhibition of the reflexes (t=5.590, P<0.05), independent of the orientations of the other leg. We concluded that sensory inflow from the moving leg induces presynaptic inhibition in the stationary leg, that a complex transformation of the sensory input in the spinal cord or brain underlies the tonic crossed inhibition and phasic ipsilateral inhibition, and that descending motor commands exert a powerful control over these sensorimotor modulatory mechanisms.     

Pharmacokinetics of intravenous and oral bolus doses of L-carnitine in healthy subjects

Summary The pharmacokinetics of single intravenous and oral doses of L-carnitine 2 g and 6 g has been investigated in 6 healthy subjects on a low carnitine diet.Carnitine was more rapidly eliminated from plasma after the higher dose. Comparing the 2-g and 6-g doses, the t_1/2 of the elimination phase () was 6.5 h vs 3.9 h, the elimination constant was 0.40 vs 0.50 h^–1 and the plasma carnitine clearance was 5.4 vs 6.11 × h^–1 (p<0.025), thus showing dose-related elimination.Saturable kinetics was not found in the range of doses given. The apparent volumes of distribution after the two doses were not significantly different and they were of the same order as the total body water. Urinary recoveries after the 2-g and 6-g doses were 70% and 82% during the first 24 h, respectively.Following the two oral dosing, there was no significant difference in AUCs of plasma carnitine. Urinary recoveries were 8% and 4% for the 2-g and 6-g doses during the first 24 h. The oral bioavailability of the 2-g dose was 16% and of the 6 h dose 5%. The results suggest that the mucosal absorption of carnitine is already saturated at the 2-g dose.     

Role of dietary fat in calorie intake and weight gain

This paper reviews the literature on the role of dietary fat in calorie intake and body weight gain in humans and laboratory animals. An overview of 40 animal studies which compared growth on high-fat (HF) and high-carbohydrate (HC) solid/powdered diets indicated that the HF diet elicited greater weight gain in 33 out of 40 studies. Enhanced growth on the HF diet was often, but not exclusively, attributable to greater caloric intake. Additional evidence for the growth-enhancing effect of HF diets emerges from "diet option" and "supermarket" feeding studies in rats, and experimental and epidemiological studies in humans. Three principal factors that contribute to the different responses to HF and HC diets are (a) caloric density, (b) sensory properties and palatability, and (c) postabsorptive processing. It is concluded that both calorie intake and metabolic energy expenditure are biased towards weight gain when a HF diet is consumed, and that the high caloric density of high-fat diets plays a primary role in weight gain. Humans may be biologically predisposed to gain weight when a HF diet is consumed.     

The breakdown of Fitts' law in rapid,reciprocal aiming movements

According to Fitts' law, there is speed-accuracy trade-off in a wide variety of discrete aiming movements. However, it is unknown whether the same law applies to cyclic aiming movements. In the present study, a comparison is made between discrete versus cyclic aiming movements. A group of 24 healthy participants made graphical pen movements in 12 different aiming tasks in which successive finger and wrist movements were emphasized, consecutively executed as discrete and cyclic movements and varying in three target widths. In the cyclic condition, aiming movements consisted of back-and-forth movements that were performed in immediate succession for 20 s. In the discrete condition, back-and-forth aiming movements were drawn as 20 single strokes, starting after a go signal and stopping after reaching the target area. The targets had various levels of spatial accuracy and the movements had different directions (from lower left to upper right; from lower right to upper left) elicit either predominantly wrist or finger movements. The amount of information processed per unit of time (bits per second; index of performance, IP), tangential velocity, the pen pressure, and the ratio of peak-over-mean velocity were studied to gain understanding about the differences in control between discrete and cyclic movements. It was found that the IP and movement velocity were almost twice as large in cyclic versus discrete movements. In contrast, the axial pen pressure and the ratios of peak-over-mean velocity were much lower in cyclic movements (1.24 N versus 0.94 N; 2.26 N versus 1.81 N). The results of our study indicate that the predicted constant IP does not hold for rapid cyclic aiming movements and that speed-accuracy trade-off is different. It is concluded that cyclic movements exploit the energetic and physiological properties of the neuromotor system. Expected differences in brain activity related to discrete and cyclic aiming movements are discussed as well as several neurophysiological mechanisms, which predict more economic force recruitment and information processing in cyclic than in discrete movements.     

Lipopolysaccharide Induces CD25-Positive, IL-10-Producing Lymphocytes Without Secretion of Proinflammatory Cytokines in the Human Colon: Low MD-2 mRNA Expression in Colonic Macrophages

Despite the huge number of colonized Gram-negative bacteria in the colon, the normal colon maintains its homeostasis without any excessive immune response. To investigate the potential mechanisms involved, human colonic lamina propria mononuclear cells (LPMCs) obtained from uninflamed mucosa were cultured with lipopolysaccharide (LPS) prepared from Bacteroides vulgatus (BV-LPS) or Bacteroides fragilis (BF-LPS), as representatives of indigenous flora, or pathogenic Salmonella minnesota (SM-LPS). Colonic LPMCs failed to produce inflammatory cytokines in response to any type of LPS. Colonic macrophages barely expressed mRNA for MD-2, an essential association molecule for LPS signaling via Toll-like receptor 4. Further, BV-LPS induced CD25 and Foxp3 expression in lymphocytes and CD4(+)CD25(+) cells expressed IL-10 mRNA. Thus, the low expression of functioning LPS receptor molecules and induction of IL-10-producing CD4(+)CD25(+) lymphocytes by indigenous LPS may play a central role in the maintenance of colonic immunological homeostasis.