The use of a selective serotonin reuptake inhibitor decreases heavy alcohol exposure-induced inflammatory response and tissue damage in rats.

Alcohol intoxication and psychiatric medication overdoses, including antidepressants, are common emergency room events. Heavy alcohol and antidepressant exposure are able to induce changes in cytokines disturbing normal physiology. We examined the inflammatory and physiological effects of selective serotonin reuptake inhibitor (SSRI) medication after heavy alcohol exposure. Rats were randomly divided into Alc (EtOH 5g/kg, intravenous infusion for 3 h), SSRI (paroxetine oral intake) and Alc+SSRI groups. Serum samples were collected to measure blood ethanol, aspartate transferase, alanine transferase, creatine phosphokinase, lactate dehydrogenase, amylase, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels. Lactate dehydrogenase levels in bronchoalveolar lavage fluid were also examined. Liver, pancreas and lungs were removed after sacrifice and any pathological changes were catalogued. Ethanol infusion resulted in blood levels of ethanol of >100 mg/dL after ethanol infusion. Serum levels of aspartate transferase, alanine transferase, creatine phosphokinase, lactate dehydrogenase, amylase, TNF-α and IL-6 in the Alc+SSRI group were lower than in the Alc group. Moreover, pathological damages to the liver, pancreas and lungs were slightly lower in the Alc+SSRI group than in the Alc group. These findings suggested that SSRI is able to decrease the release of pro-inflammatory cytokines and thereby reduce liver and pancreas damage after heavy alcohol exposure.

MicroRNA-101-mediated Akt activation and estrogen-independent growth.

MicroRNAs are gene regulators that work through a posttranscriptional repression mechanism. Dysregulation of microRNA expression could lead to a variety of disorders, in particular, human cancer, and has also been implicated in antihormone therapy resistance. However, little is known whether microRNAs have a role in estrogen-independent growth, leading to tamoxifen resistance in estrogen receptor (ER)-positive tumors. In this study, we use an in vivo selection system against a microRNA library using the MCF-7 model and demonstrate that miR-101 promotes estrogen-independent growth and causes the upregulation of phosphorylated Akt (pAkt) without impacting the ER level or activity. Importantly, although miR-101 suppresses cell growth in normal estradiol (E2)-containing medium, it promotes cell growth in E2-free medium. Moreover, estrogen deprivation greatly enhances miR-101-mediated Akt activation. Finally, we show that MAGI-2 (membrane-associated guanylate kinase), a scaffold protein required for PTEN (phosphatase and tensin homolog) activity, is a direct target for miR-101; suppression of MAGI-2 by miR-101 reduces PTEN activity, leading to Akt activation. Taken together, these results not only establish a role for miR-101 in estrogen-independent signaling but also provide a mechanistic link between miR-101 and Akt activation.

Lack of exercise decreases survival and increases organ damage after hemorrhagic shock in rats.

Inflammatory response secondary to hemorrhagic shock (HS) frequently precedes multiple organ failure and death in trauma patients. Researchers have recognized that exercise benefits immune function. However, the effects of exercise on HSinduced death and organ damage are unknown. In this study, the authors aimed to explore the effects of exercise on survival rate and organ injury after HS. Rats were divided into exercise and nonexercise groups. The exercise group received running training 30 min/day five times/week for 4 weeks. After 4 weeks, researchers withdrew 60% of total blood volume in both groups to mimic HS. Levels of blood aspartate transferase (GOT), alanine transferase (GPT), blood urea nitrogen (BUN), creatinine (Cr), lactic acid dehydrogenase (LDH), creatine kinase-myoglobin (CK-MB), blood glucose, and lactate were measured. The survival rate and injury scores for the liver, kidney, and lung were examined 48 hr after HS. Physical activity was measured in surviving rats from the 3rd to the 7th day after HS. Exercise training significantly increased the survival rate (75% for the exercise group vs. 50% for the nonexercise group) after HS and decreased organ injury. In addition, the exercise group was more active than the nonexercise group after HS.

Physiological and chemical indicators for early and late stages of sepsis in conscious rats.

Endotoxin shock is a major cause of death in patients with septicemia. Endotoxin induces nitric oxide (NO) production and causes tissue damage. In addition, the release of oxygen free radicals has also been observed in endotoxin shock and was found to be responsible for the occurrence of multiple organ failure. The purpose of the present study was to evaluate suitable indicators for early and late stages of endotoxin shock. The experiments were designed to induce endotoxin shock in conscious rats by means of an Escherichia coli lipopolysaccharide (LPS) injection. Arterial pressure (AP) and heart rate (HR) were continuously monitored for 72 h after LPS administration. The maximal decrease in AP and increase in HR and nitrate/nitrite level occurred at 9-12 h following LPS administration. The white blood cell (WBC) count had decreased at 3 h. Hydroxyl radical (methyl guanidine, MG) decreased rapidly after LPS administration. Plasma levels of blood urea nitrogen (BUN), creatinine (Cr), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and glutamic oxaloacetic transaminase increased before the rise of amylase. Our results suggest that changes in AP, HR, WBC, free radicals, and chemical substances (BUN, Cr) can possibly serve as approximate indicators for the early stage of endotoxin shock. Severe multiple organ damage may be caused by amylase release in the late stage of endotoxin shock.

Spectro-temporal modulation transfer functions and speech intelligibility.

Detection thresholds for spectral and temporal modulations are measured using broadband spectra with sinusoidally rippled profiles that drift up or down the log-frequency axis at constant velocities. Spectro-temporal modulation transfer functions (MTFs) are derived as a function of ripple peak density (omega cycles/octave) and drifting velocity (omega Hz). The MTFs exhibit a low-pass function with respect to both dimensions, with 50% bandwidths of about 16 Hz and 2 cycles/octave. The data replicate (as special cases) previously measured purely temporal MTFs (omega = 0) [Viemeister, J. Acoust. Soc. Am. 66, 1364-1380 (1979)] and purely spectral MTFs (omega = 0) [Green, in Auditory Frequency Selectivity (Plenum, Cambridge, 1986), pp. 351-359]. A computational auditory model is presented that exhibits spectro-temporal MTFs consistent with the salient trends in the data. The model is used to demonstrate the potential relevance of these MTFs to the assessment of speech intelligibility in noise and reverberant conditions.