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Patients with major depressive disorder (MDD) exhibit several clinical symptoms including difficulties in flexible thinking. Flexible thinking mainly relies on a cognitive ability called shifting; however, the mechanisms underlying shifting in patients with MDD have not yet been clarified. Therefore, we conducted a preliminary intervention study to clarify the association between depression and shifting ability. We examined the hemodynamic responses in the frontal regions during the shifting task using functional near-infrared spectroscopy (fNIRS) in 21 patients with MDD who were treated using high-frequency repetitive transcranial magnetic stimulation (rTMS). Behavioral performance on the shifting task did not change between pre- and posttreatments, whereas patients who responded well to rTMS treatment showed a significant decrease in hemodynamic responses posttreatment. On the other hand, the poor responders did not show significant changes in the hemodynamic responses between pre- and posttreatments. These results suggest that the good responders were successfully remedied with rTMS treatment and did not need effortful activity in frontal regions for shifting, which made their brain activity more efficient., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Pharmacokinetic (PK) data for antithrombin III (AT) are limited in the critical patients. We therefore performed PK analysis using a two-compartment model and also examined whether plasma AT activity would change depending on two administration methods, AT agent at 500 U/8 h (divided group) or 1,500 U/24 h (combined group) for 3 days, a regulated dosage for disseminated intravascular coagulation (DIC) treatment in Japan, in critical patients with DIC. Clinical prospective randomized study. A high care unit in a university hospital. Twenty-four consecutive critical patients with DIC. Ages ranged from 34 to 91 years. Acute physiology age and chronic health evaluation II scores were 25 to 35. Antithrombin III activities in the combined group caused remarkable transient increases but returned to near the preadministration level 24 h after the infusion. Antithrombin III level in the divided group showed small elevations on each session; therefore, steady increases were found after serial administrations of the agent. On the third day, AT trough activities in the divided group were significantly higher than those in the combined group (P = 0.005). However, peak AT activities in the combined group after AT administration were higher than those in the divided group throughout the study (P = 0.024). Aggravation of bleeding tendency occurred more frequently in the combined group (P = 0.03). Half-life times on the distribution phase in both groups were remarkably shorter than those of previously reported control in congenital AT deficiency. This suggests an increased vascular permeability in the critical patients in this study. Distribution volume in the patients here increased significantly as compared with the previous controls. This is the first PK report using a two-compartment model to demonstrate that remarkable increases in vascular permeability and distribution volume occur in critical patients with DIC, and if the same dose is administered intermittently in such PK situation, AT administration in divided manner can maintain plasma AT trough activity higher than that in the combined method.

Background: Despite the availability of a variety of immunosuppressive agents, acute rejection and infection after organ transplantation remain serious problems., Methods and Results: We examined the effect of macrophage colony-stimulating factor (M-CSF) on the production of tumor necrosis factor (TNF) in a Bacille de Calmette Guérin-lipopolysaccharide-challenged mouse model. Both serial and repeated injections of M-CSF inhibited TNF production in a dose-dependent manner. Electrophoretic mobility shift assay showed that M-CSF-induced inhibition of TNF production was a result of suppression of nuclear factor-kappaB. High-dose M-CSF significantly prolonged skin graft survival in mice with orthotopic transplantation compared with the control and low-dose M-CSF groups. The combined administration of low-dose M-CSF and cyclosporine also significantly prolonged graft survival compared with the control and low-dose single agent-treated groups., Conclusions: Our results indicate that M-CSF at a high dose is a potent inhibitor of cytokine production and can potentially be used as an immunosuppressive agent for allograft rejection.

Electrohydraulic total artificial heart (EHTAH) and electrohydraulic ventricular assist device (EHVAD) systems have been developed in our institute. The EHTAH system comprises a pumping unit consisting of blood pumps and an actuator, as well as an electronic unit consisting of an internal controller, internal and external batteries, and transcutaneous energy transfer (TET) and optical telemetry (TOT) subunits. The actuator, placed outside the pericardial space, reciprocates and delivers hydraulic silicone oil to the alternate blood pumps through a pair of flexible oil conduits. The pumping unit with an external controller was implanted in 10 calves as small as 55 kg. Two animals survived for more than 12 weeks in a good general condition. The assumed cardiac output ranged between 6 and 10 L/min, the power consumption was 12-18 W, and the energy efficiency was estimated to be 9-11%. Initial implantation of subtotal system including electronic units was further conducted in another calf weighing 73 kg. It survived for 3 days with a completely tether free system. The EHVAD system is developed by using the left blood pump and the actuator of the EHTAH, which were packaged in a compact metal casing with a compliance chamber. In vitro testing demonstrated maximum output more than 9 L/min and more than 13% maximum efficiency. The initial animal testing lasted for 25 days. These results indicate that our EHTAH and EHVAD have the potential to be totally implantable systems.

Objective: Therapeutic moderate hypothermia has the potential for neuronal protection against brain injury. Microglia, a type of immune-related cell in the brain, may play a certain role in neuronal damage subsequent to injury. We examined the effects of culture temperature changes from 37 degrees C to 33 degrees C or 30 degrees C on mediator release, including nitric oxide, interleukin-6, and tumor necrosis factor-alpha from lipopolysaccharide-stimulated microglia harvested from neonatal rats., Design: Laboratory study., Setting: University medical school., Subjects: Microglial cells isolated from primary cultures of rat brains., Interventions: The production of nitric oxide was measured by a nitrite accumulation method in a culture medium, whereas cytokines, interleukin-6, and tumor necrosis factor-alpha were measured by enzyme-linked immunosorbent assay., Measurement and Main Results: At 30 degrees C and 33 degrees C, nitric oxide production stimulated by lipopolysaccharide decreased to 10 and 30% of control (37 degrees C), respectively, 24 hrs after the stimulation, and the decrease was sustained for 48 hrs. Interleukin-6 production at 30 degrees C and 33 degrees C was also reduced to 30% of control 6 hrs after the activation. Such responses lasted throughout the study. However, tumor necrosis factor-alpha release at 30 degrees C and 33 degrees C was depressed for only 6 hrs after stimulation, followed by subsequent elevation to concentrations similar to those at 37 degrees C. Microglial morphologic activation, showing changes from round to bipolar, reached a peak at 6 hrs in the 37 degrees C group, returning to round 12 hrs after lipopolysaccharide application. In 30 degrees C and 33 degrees C, the zenith was detected at 6 hrs, with activation remaining even 12 hrs after the stimulation, suggesting prolongation of the microglial response to lipopolysaccharide, which was inconsistent with changes in tumor necrosis factor release., Conclusions: Decreasing culture temperature inhibits the production of nitric oxide and interleukin-6 from activated microglia. Differences were found in the degree or time course change between tumor necrosis factor-alpha and the other mediators. Also, the time course of morphologic changes in microglia was dependent on culture temperature. Further studies are required to define the mechanisms for such differences in mediator release from cooled microglia and also to clarify the inconsistency between morphologic change and its function in the cell.

To define a mechanism for the pressor effects of thyrotropin-releasing hormone (TRH), we evaluated changes in mean blood pressure (MBP) when a synthetic form of TRH (0.1 mg/kg, i.v.) was injected into two types of comatose patients: vegetative and brain dead. The patients in the vegetative group (n = 7, age 58 +/- 6) retained spontaneous respiration and brainstem function, whereas the brain-dead (BD) patients (n = 7, age 68 +/- 4) lacked these functions. In the vegetative group, TRH caused significant increases in MBP (from 91 +/- 8 mm Hg to 110 +/- 10 mm Hg) at 2 min after the injection [p < 0.05, analysis of variance (ANOVA) with a Scheffé F-test]. In contrast, five of the seven BD patient showed no alterations in the measured parameter in response to the TRH injection. However, the remaining two BD patients, who had spinal reflexes, exhibited an elevation in MBP. In such BD patients, baroreceptor reflex function was virtually absent, suggesting that the blood pressure regulation mediating through the baroreceptor reflex system might be abolished. These results indicate that in comatose patients, the hemodynamic effects of TRH may differ depending on impairments in the central nervous system; the results support previous reports indicating a mediation of the central sympathetic nervous system in the development of pressor effects of TRH. Furthermore, because brain-dead patients with spinal reflexes showed hypertensive responses to TRH, there is a possibility that these responses may have resulted from an activation of TRH receptors in the spinal cord.

The effect of low and high concentrations of halothane, enflurane, and isoflurane on posttraining memory function was studied in male ddN mice. Mice were trained to escape an aversive electric foot shock as an unconditioned stimulus within 3 s after being exposed to light and a buzzer as a conditioned stimulus. Immediately after training (first session: 30 trials), the animals were exposed to halothane, enflurane, or isoflurane for 120 min and then were tested again on the avoidance task (second session: 30 trials) 22 h after cessation of exposure. The performance ratios, [B/A] (i.e., A is the score in the first session, and B the score in the second) were compared between the anesthetized groups and their respective control (nonanesthetized) groups. Mean performance ratios in the control groups ([B/A]c) ranged from 136.8% to 163.9% and those in the anesthetized groups ([B/A]a) ranged from 151.4% to 174.7%. [B/A] in each anesthetized group exceeded [B/A] in its corresponding control group. [B/A]a significantly exceeded [B/A]c by 13.1% in the 1.23 minimum alveolar concentration (MAC) enflurane group (P < 0.05) and by 12.4% in the 0.29 MAC isoflurane group (P < 0.05). These results suggest that posttraining exposure to volatile anesthetics facilitates memory.

A 46-year-old female motorcyclist, who suffered injuries to the brain stem in a traffic accident, showed hypotensive and bradycardiac responses to thyrotropin-releasing hormone (TRH) given to counter consciousness disturbance. The cardiodepressive responses to TRH were reduced with i.v. pretreatment with atropine sulfate, suggesting an involvement of the vagal nervous system in the development of the responses. Furthermore, this patient had complicated impairments in the sympathetic nervous system, which were revealed by the results of testing baroreceptor reflex sensitivity to pharmacological alterations in blood pressure. We thus speculate that the hypotensive and bradycardiac effects of TRH observed in this patient may result from derangements of the sympathetic nervous system caused by the injuries. This case report is believed to be a novel description of the cardiodepressive effects of TRH.

In eight anesthetized ventilated goats, the hemodynamic effect of isoproterenol (ISU), dopamine (DOP), norepinephrine (NE), nitroglycerin (NTG), and Ringer's lactate (RL) infusion was evaluated after inducing acute pulmonary hypertension (PHN) to decrease cardiac output. Therapy with ISU significantly (p less than .05) increased cardiac output, but also increased transmural right ventricular end-diastolic pressure (RVEDPTM) and heart rate (HR) and decreased stroke volume (SV) and right ventricular ejection fraction (RVEF). NE increased cardiac output, mean arterial pressure (MAP), systemic vascular resistance (SVR), and RVEF. DOP decreased pulmonary vascular resistance (PVR) and increased cardiac output, MAP, and RVEF, but also significantly increased HR. NTG increased cardiac output and RVEF while decreasing SVR and PVR. Intravascular volume expansion by RL infusion increased cardiac output, SV, and RVEDPTM and decreased HR and PVR. The results of this study indicate that volume loading may be the treatment of choice to restore cardiac output in the face of acute PHN. NE and NTG may be effective as an adjunct therapy. Although ISU and DOP increase cardiac output, the concomitant elevation in HR is undesirable.

Acute alveolar injury induced by subcutaneous injection of N-nitroso-N-methylurethane (NNNMU) closely resembles the pathology of human adult respiratory distress syndrome (ARDS). However, its effects on cardiovascular function have not been evaluated. We measured hemodynamic variables and venous admixture (Qsp/Qt at FIO2 0.21) and shunt fraction (Qsp/Qt at FIO2 1.0) in 7 dogs. The measurements were repeated when a single subcutaneous injection of 8.0 mg/kg NNNMU decreased PaO2 on room air to 40 torr (phase I) and 30 torr (phase II). Within 5 to 7 days after injection, PaO2 decreased to 40 torr, Qsp/Qt at FIO2 0.21 increased from 0.18 to 0.70, Qsp/Qt at FIO2 1.0 increased to 0.55, and pulmonary vascular resistance index (PVRI) increased from 213 +/- 37 to 407 +/- 142 dyne X sec/cm5 X m2 (p less than .05). However, a decrease in mean arterial pressure (MAP) from 153 +/- 16 to 131 +/- 32 mm Hg was the only significant hemodynamic change. At phase II, decreased systemic vascular resistance index (SVRI) was the only significant hemodynamic alteration. We conclude that single subcutaneous injection of NNNMU produces hemodynamic and pulmonary dysfunction similar to that seen in human ARDS. This acute lung-injury model may be useful for evaluating different ARDS therapies.