Topically injected adrenocorticotropic hormone induces mechanical hypersensitivity on a full‐thickness cutaneous wound model in rats

Cutaneous wound pain causes physical and psychological stress for patients with wounds. Previous studies reported that stress induces hyperalgesia and deteriorates wound healing. However, the effect of the stress response such as in hypothalamic‐pituitary‐adrenal (HPA) axis on local wound area is unclear. We aimed to investigate the effects of a stress response on the mechanical withdrawal threshold in the local wound area and describe the identification of a wound pain exacerbation. We topically injected adrenocorticotropic hormone (ACTH) into the granulation tissue of full‐thickness cutaneous wound model rats on the fifth day postwounding and measured the mechanical withdrawal thresholds, cytochrome P450 2Bs levels and concentration of 5,6‐epoxyeicosatrienoic acid in wound exudate. We found that ACTH induced mechanical hypersensitivity at 4 and 6 hours after injection (P = .004 and .021, respectively), and increased gene expression of cytochrome P450 2B12 expression (P = .046). Concentration of 5,6‐EET in the wound exudate was moderately correlated with the mechanical withdrawal threshold (r = ?.630). Finally, the mechanical withdrawal threshold in the 5,6‐EET group was significantly lower than that in the control group at 2 hours after the injection (P = .015). We propose that 5,6‐EET is one of the most promising contributors to the wound pain exacerbation. These findings could guide clinical wound and pain management.     

Impact of mediastinal lymph node dissection on octogenarians with non-small cell lung cancer

Objective: Impacts of mediastinal lymph node dissection on a patient’s course after pulmonary resection is unclear in octogenarians with non-small cell lung cancer. Methods: Retrospectively identified subjects included 39 octogenarians and 1 nonagenarian, with grades according to the Charlson Comorbidity Index ranging from only 0 to 2. We performed mediastinal lymph node dissection in 19 patients (D group), and just lymph node sampling biopsy in the other 21 (S group). We compared clinicopathologic features and outcome after surgery between both groups. Results: Deterioration of performance status at the time of discharge, evident in 17 patients overall, was significantly more frequent in the D group. Postoperative complications occurred in 27 patients overall and there was no significant difference between the two groups. Survival rates in younger patients at 1, 3, and 5 years were 86, 59, and 49%, respectively; in octogenarians these were 83, 58, and 42% (no significant difference). Nor did survival differ significantly by surgical management of mediastinal lymph nodes; 1-, 3-, and 5-year survival rates were 94, 63, and 40%, respectively in the D group and 78, 66, and 43%, respectively in the S group. Conclusion: Octogenarians with non-small cell lung cancer should be treated by urgent pulmonary resection whenever possible. Since mediastinal lymph node dissection has little effect on long-term survival or the carried risk of worsening performance status at discharge, pulmonary resection without complete mediastinal lymph node dissection should be considered.     

Properties of neuronal activity related to a visual reaction time task in the monkey prefrontal cortex

1. Quantitative properties of neuronal activity related to a visual reaction time task were studied in the monkey prefrontal cortex. The task consisted of an initial waiting phase (3.0-s period), a warning phase (green lamp, a variable period of 1.5-3.5 s), a go phase (red lamp), and a reward phase. 2. A total of 189 task-related neurons showed 233 changes in discharge rates during the warning (n = 86), GO (n = 103), and reward (n = 44) phases of the task. Most of the task-related neurons (145/189, 77%) showed changes during only one of the task phases, and were designated W (warning phase)-type (n = 42), GO (go phase)-type (n = 59), and RE (reward phase)-type (n = 44) neurons. The remainder (n = 44, 23%) showed changes during both the warning and the go phases, and were designated WG (warning and go phase)-type neurons. In each phase, onset latencies, peak latencies, and decay times of each change were measured and compared. 3. The changes during the warning phase (n = 86) were separated into three groups based on decay time; that is, phasic changes (n = 31), phasic-tonic changes (n = 23), and tonic changes (n = 32). Onset latencies and peak latencies were homogeneously distributed, and there were no clear groupings, although phasic and phasic-tonic changes tended to show shorter latencies than tonic changes. 4. The changes during the go phase (n = 103) did not show distinct differences, either in terms of decay time or of latency. The changes during the go phase showed various degrees of coupling to both the visual go signal (GS) and lever-release hand movement. To quantitate the coupling, a value to indicate the degrees of coupling (coupling index) was calculated. The changes coupled more strongly to the GS (cue coupled), those coupled more closely to the lever release (movement coupled), and intermediate changes could be distinguished from each other. The cue-coupled changes showed shorter latencies from the time onset of the GS than the movement-coupled changes, and the intermediate changes showed intermediate latencies. The decay time and the duration of the intermediate changes were longer than those of the cue-coupled changes and the movement-coupled changes. 5. The properties of WG-type neurons were compared with those of W-type and GO-type neurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Blocking effect of 1389-S on the sodium current in isolated guinea-pig ventricular myocytes

Under whole cell patch conditions, 1389-S blocked the INa in guinea-pig ventricular myocytes under steady state conditions (Kdrest = 30 microM, Kdi = 2.4 microM) with a shift of the inactivation curve to the hyperpolarizing direction. Both brief and long conditioning pulses could produce a use-dependent block of 1389-S. These results suggest that 1389-S had a higher affinity to the inactivated than to the rested state under steady state conditions and had a higher affinity to the activated state during train pulses as well as to the inactivated state, making channels unavailable for conduction upon activation.     

Catecholamine sensitivities of neurons related to a visual reaction time task in the monkey prefrontal cortex

1. Using microiontophoretic techniques and conscious monkeys, sensitivities to noradrenaline (NA) and dopamine (DA) of neurons of the prefrontal cortex (PFC), which showed changes in activity during a visual reaction time task, were investigated. The visual reaction time task was initiated by the pressing of a lever and consisted of four phases: an initial waiting phase of 3.0 s, a warning phase (green light of variable duration of 1.5-3.5 s), a lever release go phase (red light), and a final reward phase. 2. A total of 153 neurons, which showed changes in activity during one or two phase(s) of the task, were sampled. Of these neurons, 39 changed their activity during the warning phase, 48 changed their activity during the go phase, 38 changed their activity during both the warning and the go phases, and 28 changed their activity during the reward phase. 3. Iontophoretically applied NA and DA (with a current of 30-70 nA, but usually with a current of 50 nA) induced excitatory and/or inhibitory responses in 141 of the 153 task-related neurons. NA induced responses in 99 neurons, and these responses were predominantly inhibitory (n = 90). DA induced excitatory (n = 62) and inhibitory (n = 30) responses in 92 neurons. Fifty neurons were sensitive to both NA and DA. 4. The neurons showing changes in activity during different phases of the task showed different sensitivities to NA and DA applied with 50 nA. The warning phase-related neurons were primarily sensitive to NA (36/39), the go phase-related neurons were primarily sensitive to DA (44/48), neurons related to both the warning and go phases were sensitive to both NA and DA (33/38), and the reward phase-related neurons were primarily sensitive to NA (23/28). 5. In the neurons that showed increased changes in activity during the warning phase, NA reduced the background activity to a greater extent than the activity during the warning phase and increased the ratio of the warning phase-related activity to the background activity. In the neurons that showed decreased changes during the warning phase, NA reduced the activity during the warning phase to a great extent than the background activity, and increased ratio of the background activity to the warning phase-related activity. Furthermore, the latency of onset of the change in activity tended to become shorter by application of NA. Thus, NA enhanced the change in activity during the warning phase, irrespective of whether the direction of the change was toward an increase or a decrease.(ABSTRACT TRUNCATED AT 400 WORDS)     

Left anterior hemiblock studied by computer graphic electrocardiography

In order to find the three-dimensional distribution of ventricular depolarization potentials in left anterior hemiblock (LAHB) diagnosed by the conventional scalar ECG, 7 subjects with LAHB aged 9 to 62 years old who were otherwise healthy were studied by computer graphic electrocardiography (CGECG).Two modes of the initial ventricular depolarization (IVD) were noted. (1) The IVD appeared irregularly and separately on the mid- to lower central region of the anterior body surface. (2) The IVD appeared in a form rather like a parallelogram on the central region of the anterior body surface. Both (1) and (2) potentials propagated toward the left middle, lower, and lateral regions of the anterior body surface as normally observed; however, they were far lower in voltage than those observed in intact subjects.From the results, it has been concluded that LAHB may be, not a block, but rather a defective ventricular septal conduction.Presented at the 34th Annual Congress, International College of Angiology, Budapest, Hungary, July 1992.     

Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis

Ligation of the chemokine receptor CCR2 on monocytes and macrophages with its ligand CCL2 results in activation of the cascade consisting of phosphatidylinositol-3-OH kinase (PI(3)K), the small G protein Rac and lamellipodium protrusion. We show here that a unique clathrin heavy-chain repeat homology protein, FROUNT, directly bound activated CCR2 and formed clusters at the cell front during chemotaxis. Overexpression of FROUNT amplified the chemokine-elicited PI(3)K-Rac-lamellipodium protrusion cascade and subsequent chemotaxis. Blocking FROUNT function by using a truncated mutant or antisense strategy substantially diminished signaling via CCR2. In a mouse peritonitis model, suppression of endogenous FROUNT markedly prevented macrophage infiltration. Thus, FROUNT links activated CCR2 to the PI(3)K-Rac-lamellipodium protrusion cascade and could be a therapeutic target in chronic inflammatory immune diseases associated with macrophage infiltration.     

Catecholaminergic neurons in the brain-stem and sleep apnea in SIDS victims

Background: Tyrosine hydroxylase (TH) is a specific marker for catecholaminergic neurones. Some reports have demonstrated a decrease of TH in the sudden infant death syndrome (SIDS) compared with controls. To further investigate this, the correlation between TH and sleep apnea was investigated here. Materials and methods: Among 27,000 infants studied prospectively to characterize their sleep–wake behavior, 38 infants died under 6 months of age. They included 26 cases of SIDS. All the infants had been recorded during one night in a pediatric sleep laboratory some 3–12 weeks before death. The frequency and the duration of sleep apnea were analyzed. The brain-stem material was collected and subjected to immunohistochemical studies for TH. The density of TH-immunoreactive neurons was measured in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguus and the ventrolateral medulla (VLM) in the medulla oblongata. Correlation analyses were carried out between the density of TH-immunoreactive neurons and the data from the sleep apnea studies. Results: There was no SIDS specific correlation between TH-immunoreactive neurons in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguus and the ventrolateral medulla in the medulla oblongata and the frequency and duration of sleep apnea. Conclusions: No significant association between the pathological data and the physiological data refers to TH-positive neurons in the medulla oblongata in SIDS victims.     

Correlation between the Ki-67 antigen in the brainstem and physiological data on sleep apnea in SIDS victims

Background: The Ki-67 antigen appears in all human proliferating cells during late G1, S, M and G2 phases of the cell cycle, but is consistently absent in the G_o phase (noncycling) cells. The correlation between Ki-67 in the brainstem and sleep apnea in victims of the sudden infant death syndrome (SIDS) was investigated to elucidate cell kinetics in the brainstem of this condition, which is still the main cause of postneonatal infant death. Materials and methods: Twenty-six cases of SIDS occurred among 38 infants dying under 6 months of age in a cohort of 27,000 infants studied prospectively to characterize their sleep–wake behavior. All the infants had been recorded during one night in a pediatric sleep laboratory some 3–12 weeks before death. The frequency and duration of sleep apnea were analyzed. At autopsy, brainstem material was collected and immunohistochemistry for Ki-67 was carried out. The density of Ki-67-positive neurons was measured semiquantitatively. Correlation analyses were carried out between the density of Ki-67-positive neurons and the data on sleep apnea. Results: Except in two cases in SIDS victims and in one control, the detection of Ki-67 was negative. No correlation analysis between the Ki-67 and of sleep apnea was found. Conclusions: There were no abnormal cell kinetics detected by the demonstration of Ki-67 antigen in the brainstems of SIDS victims.