Severe cerebral edema associated with exertional heat stroke is a major cause of death or disability. However, few studies on severe cerebral edema resulting from heat stroke have reported neuroradiological findings. Moreover, all the patients in these previous reports either died or remained severely disabled. Here, we report a case of exertional heat stroke with severe cerebral edema that probably developed or worsened due to delayed body temperature normalization. In contrast to previous reports, the patient showed complete clinical and neuroradiological recovery. This rare case suggests that severe cerebral edema could be reversed through meticulous supportive management. Moreover, it confirms the importance of rapid and effective cooling in heat stroke treatment.

Severe cerebral edema associated with exertional heat stroke is a major cause of death or disability. However, few studies on severe cerebral edema resulting from heat stroke have reported neuroradiological findings. Moreover, all the patients in these previous reports either died or remained severely disabled. Here, we report a case of exertional heat stroke with severe cerebral edema that probably developed or worsened due to delayed body temperature normalization. In contrast to previous reports, the patient showed complete clinical and neuroradiological recovery. This rare case suggests that severe cerebral edema could be reversed through meticulous supportive management. Moreover, it confirms the importance of rapid and effective cooling in heat stroke treatment.

Increased levels of tissue corticosteroids are associated with important protective responses of critically ill patients. Critical illness and its treatment interfere with the normal corticosteroid response to illness and induce tissue corticosteroid insufficiency. Therefore, corticosteroid is commonly used in critically ill patients. In intensive care units, the main reasons for using steroids are critical illness-related corticosteroid insufficiency (CIRCI), septic shock, acute respiratory distress syndrome (ARDS), airway edema, etc. CIRCI may be suspected due to symptoms or signs such as unconsciousness, hemodynamic instability, fever, or electrolyte imbalance. An adrenocorticotropic hormone stimulation test or measurement of a random plasma cortisol level is necessary to diagnose CIRCI. Corticosteroid administration can be helpful when CIRCI is confirmed. Similar to CIRCI, corticosteroid can be used in septic shock. However, corticosteroid administration is not recommended for patients with sepsis without shock. The use of corticosteroid in patients with ARDS is still controversial. Although steroids are commonly used for critically ill patients, there are controversies related to the use of steroids in the intensive care unit. In this article, we review the physiology of the corticosteroid response to critical illness and practical issues relating to the diagnosis and treatment of corticosteroid insufficiency in critically ill patients.
Adrenal Cortex Hormones ; Adrenal Insufficiency ; Adrenocorticotropic Hormone ; Critical Illness ; Diagnosis ; Edema ; Fever ; Hemodynamics ; Humans ; Hydrocortisone ; Intensive Care Units ; Physiology ; Plasma ; Respiratory Distress Syndrome, Adult ; Sepsis ; Shock ; Shock, Septic ; Steroids ; Unconsciousness

Methamphetamine (MA) is one of the most commonly abused drugs in the world by illegal drug users. Addiction to MA is a serious public health problem and effective therapies do not exist to date. It has also been reported that behavior induced by psychostimulants such as MA is related to histone deacetylase (HDAC). MeBib is an HDAC6 inhibitor derived from a benzimidazole scaffold. Many benzimidazole-containing compounds exhibit a wide range of pharmacological activity. In this study, we investigated whether HDAC6 inhibitor MeBib modulates the behavioral response in MA self-administered rats. Our results demonstrated that the number of active lever presses in MA self-administered rats was reduced by pretreatment with MeBib. In the hippocampus of rats, we also found MA administration promotes GluN2B, an NMDA receptor subunit, expression, which results in sequential activation of ERK/CREB/BDNF pathway, however, MeBib abrogated it. Collectively, we suggest that MeBib prevents the MA seeking response induced by MA administration and therefore, represents a potent candidate as an MA addiction inhibitor.

No abstract available.
Acyclovir ; Humans

FoxO1, a member of the Forkhead transcription factor family subgroup O (FoxO), is expressed in a range of cell types and is crucial for various pathophysiological processes, such as apoptosis and inflammation. While FoxO1’s roles in multiple diseases have been recognized, the target has remained largely unexplored due to the absence of cost-effective and efficient inhibitors. Therefore, there is a need for natural FoxO1 inhibitors with minimal adverse effects. In this study, docking, MMGBSA, and ADMET analyses were performed to identify natural compounds that exhibit strong binding affinity to FoxO1. The top candidates were then subjected to molecular dynamics (MD) simulations. A natural product library was screened for interaction with FoxO1 (PDB ID-3CO6) using the Glide module of the Schrödinger suite. In Silico ADMET profiling was conducted using SwissADME and pkCSM web servers. Binding free energies of the selected compounds were assessed with the Prime-MMGBSA module, while the dynamics of the top hits were analyzed using the Desmond module of the Schrödinger suite. Several natural products demonstrated high docking scores with FoxO1, indicating their potential as FoxO1 inhibitors. Specifically, the docking scores of neochlorogenic acid and fraxin were both below -6.0. These compounds also exhibit favorable drug-like properties, and a 25 ns MD study revealed a stable interaction between fraxin and FoxO1. Our findings highlight the potential of various natural products, particularly fraxin, as effective FoxO1 inhibitors with strong binding affinity, dynamic stability, and suitable ADMET profiles.