Treatment with inhaled aerosolised ethanol reduces viral load and potentiates macrophage responses in an established influenza mouse model.

AIM: Treatment options for viral lung infections are currently limited. We aimed to explore the safety and efficacy of inhaled ethanol in an influenza-infection mouse model. MATERIALS AND METHODS: In a safety and tolerability experiment, 80 healthy female BALB/c mice (20 per group) were exposed to nebulized saline (control) or three concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods, with a two-hour break between exposures. In a separate subsequent experiment, 40 Female BALB/c mice were nasally inoculated with 104.5 plaque-forming units of immediate virulence "Mem71" influenza. Infection was established for 48-h before commencing treatment in 4 groups of 10 mice with either nebulized saline (control) or one of 3 different concentrations of ethanol (40/60/80% ethanol v/v in water) for 3x30-minute periods daily over three consecutive days. In both experiments, mouse behavior, clinical scores, weight change, bronchoalveolar lavage cell viability, cellular composition, and cytokine levels, were assessed 24-h following the final exposure, with viral load also assessed after the second experiment. RESULTS: In uninfected BALB/c mice, 3x30-minute exposures to nebulized 40%, 60%, and 80% ethanol resulted in no significant differences in mouse weights, cell counts/viability, cytokines, or morphometry measures. In Mem71-influenza infected mice, we observed a dose-dependent reduction in viral load in the 80%-treated group and potentiation of macrophage numbers in the 60%- and 80%-treated groups, with no safety concerns. CONCLUSIONS: Our data provides support for inhaled ethanol as a candidate treatment for respiratory infections.

Surgical incision pain induced an increase in alcohol consumption in mice.

INTRODUCTION: Large population-based studies have suggested a link between increased alcohol use and reduced pain. In addition, these studies suggest that higher levels of pain intensity are associated with an increase in alcohol consumption and rates of hazardous drinking which potentiates the risk of developing alcohol use disorders (AUD). The mechanisms and determinants of the alcohol-pain interaction can be studied in preclinical studies. METHODS: The overall goal of this study is to use animal models to explore the impact of acute postoperative pain on alcohol intake. To achieve this, we characterized the timeline and levels of alcohol intake and preference in mice after laparotomy in the 2-bottle choice paradigm. RESULTS: Our results show that laparotomy surgery increased alcohol intake and preference in male mice but not females in the 2-bottle choice and 3-bottle choice assays. In addition, ketoprofen administration blocked the increase in alcohol consumption in male mice after laparotomy. We also found that changes in alcohol initial sensitivity and acute functional tolerance, using loss of righting reflex (LORR) response, occur after surgery in mice. CONCLUSION: Taken together, these findings suggests that sex, pain and alcohol sensitivity-related factors may modulate the relationship between alcohol consumption and pain.

[Ultrasound-guided anhydrous ethanol and microwave ablation for functional parathyroid cyst: a case report].

We report a case of functional parathyroid cyst treated by ultrasound-guided anhydrous ethanol sclerotherapy and microwave ablation. The 63-year-old female patient was diagnosed to have functional parathyroid cyst with hypercalcemia, high PTH and cystic space-occupying lesions in the neck by ultrasound, radionuclide scanning and PTH measurement of the cystic fluid. The patient refused to receive cyst resection, and anhydrous ethanol sclerotherapy with microwave ablation was performed under ultrasound guidance. The procedure was completed smoothly without any complications either during or after the operation. Follow-up examination of the patient at 18 months after the operation showed a significant reduction of the mass and normal blood calcium and iPTH levels, demonstrating a clinical cure of the patient. Ablative treatment of functional parathyroid cyst has not been documented so far. This approach provides a minimally invasive treatment modality for such cases where surgical resection is not an option, but its efficacy and safety need to be evaluated in more cases with longer follow-up time.

Ultrasound-Guided Ethanol Ablation as a Primary Treatment for Thyroglossal Duct Cyst: Feasibility, Characteristics, and Outcomes.

OBJECTIVES: To evaluate the feasibility, characteristics, and outcomes of ultrasound-guided ethanol ablation (US-EA) as a primary treatment for thyroglossal duct cysts (TGDCs). STUDY DESIGN: Prospective case series. SETTING: Single center study. METHODS: The inclusion criteria were as follows: (i) patients with TGDC aged ≥18 years, (ii) benign TGDC in imaging and cytological examinations, and (iii) patients' need for nonsurgical scarless treatment. US-EA was used as the primary treatment strategy. The primary outcome variables were the volume reduction rate (VRR) and cosmetic score at the last follow-up. RESULTS: We enrolled 28 patients with TGDC. The median TGDC volume at baseline was 6.7 mL. The median procedure time of the US-EA was 6.5 minutes. The median volumes of the cyst aspirate and injected ethanol were 4.0 and 2.0 mL, respectively. Overall, 18, 8, and 2 patients underwent 1, 2, and 3 treatment sessions, respectively. There were no complications. The median VRR was 96.2%, and the treatment success rate was 96.4%. The World Health Organization cosmetic score decreased from 4 (baseline) to 1 (after treatment) in all patients. The subjective grade for cosmetic satisfaction was satisfactory or highly satisfactory in all patients. The VRR, treatment success rate, and the number of treatment sessions did not differ as functions of the characteristics of the TGDC, including the initial volume, septation, debris, or viscosity of the cyst fluid. CONCLUSION: US-EA was feasible, safe, and effective in patients with TGDC. Therefore, US-EA can be used as a primary treatment for TGDC, evading general anesthesia and surgical scar.

Acute and chronic ethanol administration: A potential model of behavioral sensitization using wheel-running in male CD1 mice.

RATIONALE: We define behavioral sensitization as an augmented response to subsequent dosing after chronic intermittent administration of a drug. However, the biphasic effects of ethanol (EtOH), first stimulatory followed by depressive, make animal models of behavioral sensitization rare. OBJECTIVES: This study aimed to determine a dose of EtOH that did not depress wheel-running (WR) in CD1 mice and then to develop a model of EtOH-induced behavioral sensitization. METHODS: For the first part of this study, male CD1 mice (n = 24, 6/group) were administered either phosphate buffer saline (PBS), 0.5 g/kg, 1 g/kg, or 2 g/kg EtOH at a volume of 3 ml/kg, intraperitoneally (IP). Mice were divided into equal groups and received the weight-based dose once daily on Days 1, 2, 3, 4, and 5. All mice received a challenge dose of 0.5 g/kg on Day 10. In both parts of the study, mice were habituated to the running wheel for 5 min prior to dosing and wheel running was measured for 10 min after each dose. RESULTS: The acute dose-response of EtOH effects on wheel running determined a significant difference between doses in wheel running (p < 0.05), with a post-hoc analysis establishing that 0.5 g/kg EtOH resulted in significantly more WR compared to 2 g/kg EtOH (p < 0.05). The chronic study demonstrated a significant main effect of Day (1 vs. 5 vs. Challenge, p < 0.001) and an interaction between Day and Treatment, with post-hoc analysis determining the effect to be between PBS and EtOH WR on Day 5 (p < 0.05). In addition, Bonferroni post-hoc analysis determined no differences between Days in the PBS condition, but a significant difference in the EtOH condition between Day 1 and Day 5 (p < 0.001) and that difference from Day 1 persisted when comparing to the Challenge Day (p < 0.01). CONCLUSION: After chronic, intermittent, low dose administration of EtOH, male mice showed an increase in activity as measured by wheel running. Therefore, we laid the groundwork for a potentially useful rodent model for EtOH-induced behavioral sensitization.

Low versus high level of response to alcohol affects amygdala functional connectivity during processing of emotional stimuli.

BACKGROUND: Low levels of response (low LR) to alcohol predict heavy drinking and alcohol problems. Functional magnetic resonance imaging (fMRI) studies of emotion processing have shown that low LR individuals exhibit lower activation in task-related brain regions following both placebo and alcohol administration, but these studies did not examine functional brain networks that might contribute to the phenomena. The current study expands upon the earlier results by evaluating whether functional connectivity differences between the amygdala and other brain regions modulated by emotional face processing are associated with LR. Based on prior findings, we hypothesized that low LR is related to lower functional connectivity in fronto-amygdalar functional circuits, which underlie the processing of emotional stimuli. METHODS: Secondary analyses were conducted on data from a double-blind, placebo-controlled, within-subjects, cross-over study in 108 18-to-25-year-old low and high LR sex-matched pairs without alcohol use disorder at baseline. Participants performed modified emotional faces processing tasks after receiving placebo or approximately 0.7 ml/kg of ethanol. Psychophysiological interaction analyses examined functional connectivity between left and right amygdalae and related brain circuits using LR-by-alcohol general linear models. The data included 54 sex-matched pairs with 216 fMRI scans comprising alcohol and placebo conditions. RESULTS: Compared with individuals with high LR, low LR subjects demonstrated lower functional connectivity between the amygdala and the frontal lobes, insula, and parietal regions, while processing angry and happy faces. Interactions showed lower connectivity following alcohol in low LR and higher connectivity in high LR groups. CONCLUSIONS: Low LR individuals demonstrated lower functional connectivity in response both to placebo and a modest dose of ethanol. Attenuated connectivity among low LR individuals when processing emotional faces may contribute to an impaired ability to recognize alcohol intoxication in social situations and to appraise angry and happy emotions irrespective of whether alcohol is consumed.

Ultrasound-Guided Injection Treatments Versus Surgical Neurectomy for Morton Neuroma: A Cost-Effectiveness Analysis.

BACKGROUND. Morton neuroma is a common, painful disorder of the foot with multiple treatment options of varying cost and effectiveness. OBJECTIVE. The aim of this study was to determine the most cost-effective treatment pathway for symptomatic Morton neuromas when conservative management has failed. METHODS. An incremental cost-utility analysis was performed comparing a direct to surgical neurectomy strategy with three selective injection strategies in which one or more ultrasound-guided injection therapies was tried first before surgery for patients who did not respond to treatment. The three selective injection strategies were selective steroid injection, selective alcohol injection, and selective steroid/alcohol injection in which both steroid injections and alcohol sclerosing injections were trialed successively before surgical neurectomy. The direct-to-surgery approach was compared with the three different selective injection strategies and with a no-treatment strategy in a decision-analytic model for a hypothetical group of patients with symptomatic Morton neuroma in whom conservative management had failed. Model parameters, including treatment costs, effectiveness, complication rates, and health utility states, were estimated from the literature, reimbursement databases, and expert opinion. The outcome was cost per quality-adjusted life year (QALY) with a time horizon of 3 years. A societal cost perspective was adopted with a willingness-to-pay threshold of $100,000/QALY. Sensitivity analyses for key model parameters were performed. RESULTS. For the base input values, the steroid/alcohol selective injection strategy was dominant and yielded an incremental cost-effectiveness ratio of $4401.61/QALY compared with no treatment. The probabilistic sensitivity analysis supported this strategy in 74% of 10,000 simulated trials. Results were robust with low sensitivity to most input parameters. However, when the probability of successful alcohol injection treatment dropped below 40%, the steroid selective injection strategy became most cost-effective. CONCLUSION. A trial of ultrasound-guided injection therapies for Morton neuroma is a cost-effective strategy compared with proceeding directly to surgical neurectomy. CLINICAL IMPACT. Ultrasound-guided injection therapies are indicated as first-line treatment of patients with symptomatic Morton neuromas when conservative management fails.

Transepithelial Diluted Alcohol and Iontophoresis-Assisted Corneal Crosslinking for Progressive Keratoconus in Adults: 4-Year Clinical Results.

PURPOSE: The aim of this study was to compare the 4-year clinical outcomes of transepithelial diluted alcohol and iontophoresis-assisted corneal crosslinking (DAI-CXL) and standard corneal crosslinking (S-CXL) in adults with progressive keratoconus. METHODS: This retrospective study included 36 eyes of 36 keratoconic patients who underwent DAI-CXL (n = 18) or S-CXL (n = 18). Best spectacle-corrected visual acuity (BSCVA) and corneal topography parameters were analyzed at baseline and at 1, 2, 3, and 4 years of follow-up. Corneal demarcation line depth (DLD) at 1 month was measured, and the relation of DLD with corneal thickness (DL%) was assessed. RESULTS: BSCVA improved significantly only in S-CXL (P = 0.01). A significant decrease in maximum keratometry and mean keratometry occurred at 4 years in both groups (all P < 0.05), and these changes were similar in both groups (all P > 0.05). There was a significant reduction in the thinnest corneal thickness in S-CXL (P = 0.01); however, the mean thinnest corneal thickness in DAI-CXL remained stable (P = 0.094). Higher-order aberrations and coma aberration decreased significantly in both groups at 4 years (all P < 0.05), with a higher decrease in S-CXL (all P < 0.05). Spherical aberration showed a significant reduction only in S-CXL (P = 0.005). In contrast to the similar mean DLD in both groups, DL% in DAI-CXL was significantly greater than that in S-CXL (P = 0.032). There were no correlations between the improvement in BSCVA, maximum keratometry, mean keratometry, higher-order aberrations, and the mean DLD and DL% (all P > 0.05). CONCLUSIONS: DAI-CXL was as effective as S-CXL in arresting the progression of keratoconus and showed similar clinical results to S-CXL at the 4-year follow-up.

Profiling of extracellular vesicle-bound miRNA to identify candidate biomarkers of chronic alcohol drinking in nonhuman primates.

BACKGROUND: Long-term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it has been challenging to identify reliable biomarkers of alcohol drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle-bound microRNAs (EV-miRNAs) have been found to be consistent biomarkers of conditions that include cancer and liver disease. METHODS: In this study, we profiled the plasma EV-miRNA content by miRNA-Seq from 80 nonhuman primates after 12 months of voluntary alcohol drinking. RESULTS: We identified a list of up- and downregulated EV-miRNA candidate biomarkers of heavy drinking and those positively correlated with ethanol dose. We overexpressed these candidate miRNAs in control primary peripheral immune cells to assess their potential functional mechanisms. We found that overexpression of miR-155, miR-154, miR-34c, miR-450a, and miR-204 led to increased production of the inflammatory cytokines TNFα or IL-6 in peripheral blood mononuclear cells after stimulation. CONCLUSION: This exploratory study identified several EV-miRNAs that could serve as biomarkers of long-term alcohol drinking and provide a mechanism to explain alcohol-induced peripheral inflammation.

Behavioral genetics of alcohol's effects in three zebrafish (Danio rerio) populations.

Alcohol abuse is one of the most dangerous and serious problems for patients and society. Interpopulation studies are important in understanding how genetic background contributes to the effects of alcohol. In this study, we applied a chronic alcohol exposure protocol in three zebrafish populations (Danio rerio; both sexes; AB, TU, and outbred fish - OB). We analyzed the behavioral responses and mRNA expression involved in neurotransmitter metabolism - th1, tph1, ache, ada1, gaba1, gad1b, and bdnf. Locomotion patterns were similar between populations (increased speed after acute alcohol and unaltered locomotion after chronic and withdrawal treatments). All populations exhibited increased expression of genes associated with locomotion (th1, gad1b, and gaba1) after acute alcohol exposure. Anxiety-like responses increased in AB and TU fish during withdrawal and decreased in AB fish after acute alcohol exposure. Genes related to anxiety-like behavior (tph1 and ada1) were overexpressed in AB and TU fish after acute and withdrawal treatments, while OB fish exhibited unaltered responses. Bdnf levels decreased during withdrawal in AB and OB fish, while TU showed upregulated levels in both chronic and withdrawal treatments. Our results suggest that zebrafish populations respond differently to alcohol exposure, which may contribute to understanding the mechanisms underlying alcohol use and dependence. Moreover, we found that a more diverse genetic background (OB) was related to higher variability in behavioral and mRNA expression, demonstrating that inbred populations (AB and TU) may be useful tools in identifying alcohol use and abuse mechanisms.

Percutaneous ethanol sclerotherapy is a promising treatment for recalcitrant angiolymphoid hyperplasia with eosinophilia.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare benign vascular proliferation, which manifests as characteristic red nodules and papules, mostly located on the scalp and periauricular regions. Patients seek treatment for both aesthetic and functional reasons, as lesions may ulcerate, bleed and itch. Many therapeutic approaches have been reported, with variable success, and relapse remains a troublesome issue. The aim of this study was to report our experience treating ALHE using percutaneous ethanol sclerotherapy (PES). We present a retrospective case series of three patients treated with PES (1-2 treatment sessions each). All patients had tried and failed other treatments prior to this intervention, but following PES treatment, all patients demonstrated significant improvement, which was sustained at follow-up (range 8-17 months after first treatment). Adverse effects were tolerable and transient. This case series demonstrates PES as a promising treatment for recalcitrant ALHE.

Percutaneous ethanol injection therapy as the first line of treatment of symptomatic thyroid cysts.

BACKGROUND: Our aim was to evaluate the efficacy and security of ultrasound-guided percutaneous ethanol injection therapy (US-PEIT) for the treatment of recurrent symptomatic thyroid cysts in two high-resolution consultations of thyroid nodule in the Valencian Community. PATIENTS AND METHODS: The study comprised thirty-three consecutive patients (51 ±â€¯12 years, 76% women) with symptomatic benign thyroid cysts relapsed after drainage and benign cytology prior to treatment. Through ultrasound, maximum cyst diameter and volume were determined, and the content of the cyst was drained. We then instilled between 2 and 4 ml of ethanol (according to initial volume). We followed up with ultrasound at one, 3, 6 and 12 months and we calculated the total volume and the Volume Reduction Rate (VRR). We evaluated the perceived pain using a visual analog scale. RESULTS: The initial median cyst volume was 11.6 ml (8.5-16.5) A single session of US-PEIT was required in 22 patients (67%), two in 8 (24%) and three in 3 (9%). During PEIT, 49% of the patients experienced virtually no pain, 39% mild pain and 12% moderate pain. There were no complications. After 6 months of follow up the median VRR was 93% (84-98). All the patients achieved a volume reduction of more than 50%, 94% of more than 70% and 56% of more than 90%. Twenty-four patients completed a year of follow-up, achieving a VRR of 97% (93-98). CONCLUSIONS: In our experience US-PEIT has proven to be an effective, safe treatment of symptomatic thyroid cysts. For this reason it can be considered as the first line of treatment and included in the portfolio of services of a high-resolution consultation.

Anti-Oxidant and Anti-Inflammatory Effects of Lipopolysaccharide from Rhodobacter sphaeroides against Ethanol-Induced Liver and Kidney Toxicity in Experimental Rats.

This study aimed to investigate the protective effects of lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) against ethanol-induced hepatotoxicity and nephrotoxicity in experimental rats. The study involved an intact control group, LPS-RS group, two groups were given ethanol (3 and 5 g/kg/day) for 28 days, and two other groups (LPS-RS + 3 g/kg ethanol) and (LPS-RS + 5 g/kg ethanol) received a daily dose of LPS-RS (800 µg/kg) before ethanol. Ethanol significantly increased the expression of nuclear factor kappa B (NF-κB) and levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the liver tissue and decreased anti-oxidant enzymes. Hepcidin expression was downregulated in the liver, with increased serum levels of ferritin and iron. Prior-administration of LPS-RS alleviated the increase in oxidative stress and inflammatory markers, and preserved iron homeostasis markers. In the kidney, administration of ethanol caused significant increase in the expression of NF-κB and the levels of TNF-α and kidney injury markers; whereas LPS-RS + ethanol groups had significantly lower levels of those parameters. In conclusion; this study reports anti-oxidant, anti-inflammatory and iron homeostasis regulatory effects of the toll-like receptor 4 (TLR4) antagonist LPS-RS against ethanol induced toxicity in both the liver and the kidney of experimental rats.

Gastroprotective effect and mechanisms of Chinese sumac fruits (Rhus chinensis Mill.) on ethanol-induced gastric ulcers in mice.

This paper aimed to study the effect of the phenol-rich fraction from Chinese sumac fruits on ethanol-induced gastric ulcers in mice and to further elucidate the potential mechanisms. The results showed that the phenol-rich fraction of the fruits significantly decreased the ulcer index, restored the levels of prostaglandin E-2, heat shock protein 70, glutathione and superoxide dismutase, and reduced the malondialdehyde content. Further analyses revealed that the fraction significantly alleviated the gastric oxidative stress by upregulating the Nrf2 protein pathway to increase the HO-1 and NQO1 expression levels, suppressed the inflammation by reducing the expression levels of p-NF-κB and p-IκBα and inhibited the secretion of tumor necrosis factor-α, interleukin-1ß, and interleukin-6. In addition, the fraction remarkably prevented gastric mucous cell apoptosis by upregulating Bcl-2 and downregulating Bax and cleaved caspase3. This experiment clarified for the first time that the phenol-rich fraction from Chinese sumac fruits can prevent ethanol-induced gastric ulcers in mice by inhibiting the oxidative stress, inflammatory response and cell apoptosis. The results obtained from the current work indicated that the phenol-rich fraction from Chinese sumac fruits could be applied as a kind of natural resource for producing new functional foods to prevent and/or improve gastric ulcers induced by ethanol.

Non-Smad, BMP-dependent signaling protects against the effects of acute ethanol toxicity.

This study explores the effect of acute Ethanol (EtOH) exposure on Bone Morphogenetic Protein (BMP)-evoked intracellular signaling, and the concomitant morphological changes induced by EtOH in C2C12 cells and DRG (Dorsal root ganglion) neurons in an in vitro model related to Fetal Alcohol Syndrome Disorder (FASD). All assays were performed within 30 min of BMP stimulation to specifically investigate the earliest events occurring in BMP-evoked intracellular signaling pathways. We show that Smad phosphorylation and nuclear translocation stimulated by BMPs was not altered following acute exposure to EtOH. In contrast, acute EtOH exposure alone caused a striking concentration-dependent decrease in Akt phosphorylation, as well as a loss of adhesion in C2C12 cells. The addition of BMPs before exposure to EtOH was associated with maintenance of Akt phosphorylation, greater cell adhesion in C2C12 cells, and preservation of growth cone complexity in DRG neurons. Thus, for both C2C12 cells and DRG neurons, BMPs, acting through non-canonical BMP signaling pathways, appear to impart some protection against the profound effects of acute EtOH exposure on cellular adhesion and structure.

Intake of Lactobacillus rhamnosus GG (LGG) fermented milk before drinking alcohol reduces acetaldehyde levels and duration of flushing in drinkers with wild-type and heterozygous mutant ALDH2: a randomized, blinded crossover controlled trial.

Alcohol consumption leads to acetaldehyde accumulation, especially in people with mutant aldehyde dehydrogenase 2 gene (ALDH2). Novel strategies to promote acetaldehyde detoxification are required to prevent alcohol-related toxicity. Probiotic bacteria such as Lactobacillus rhamnosus GG (LGG) were shown to have in vitro capacity to detoxify acetaldehyde. This randomized, blinded, placebo-controlled cross-over trial investigated the effect of LGG fermented milk in people with ALDH2 polymorphisms after moderate alcohol intake. Ten healthy wild-type and ten heterozygous mutant ALDH2 Thai men were block randomized into two groups. Each group consumed a different sequence of 150 mL fermented milk containing 108 CFU mL-1 LGG and lactic-acidified milk (placebo), followed by five glasses of beer (0.4 g ethanol per kg body weight), with a one-week wash-out. Consuming LGG fermented milk before alcohol reduced areas under the response curves of blood and salivary acetaldehyde in wild-type and heterozygous mutant ALDH2 individuals (p < 0.05 and p < 0.01, respectively). Interestingly, participants with mutant ALDH2 responded better than wild-type participants for salivary acetaldehyde (90% vs. 70%, p < 0.001). Their durations of flushing were reduced when consuming LGG milk. Regardless of ALDH2 status, 105 CFU mL-1 LGG was retained in saliva at least 3.5 h after milk consumption. In conclusion, intake of LGG fermented milk before drinking alcohol reduces blood and salivary acetaldehyde levels and duration of flushing in drinkers with wild-type and heterozygous mutant ALDH2. The addition of exogenous capacity to detoxify acetaldehyde using the probiotic product could be a potential strategy to promote the alleviation of exposure to reactive and carcinogenic acetaldehyde associated with alcohol drinking in individuals with defective ALDH2 enzyme.

Antioxidant Activity Derived from Marine Green-Lipped Mussel Perna canaliculus Extracts in Mice.

This study investigates the antioxidant activities of lipid, protein, and carbohydrate extracts from the marine mollusk Perna canaliculus. Lipids were extracted using acetone, which was followed by protein extraction using the broad-spectrum enzyme Alcalase and then carbohydrate extraction using cetylpyridinium chloride. Eighty white BALB/c mice were divided into eight groups according to the administered extracts. Groups 1 and 5 were the control and toxin control groups, respectively. Groups 2, 3, and 4 were administered lipid, protein, and carbohydrate extracts, respectively. The other groups were administered P. canaliculus extracts as well as gentamicin and acetaminophen, known as ethanolic extracts, derived from Nerium oleander to induce oxidation stress. All groups showed significant improvements in body weight (p < 0.05). The lipid extract group showed a significant decrease in low-density lipoprotein cholesterol (p < 0.05) and a significant increase in high-density lipoprotein cholesterol (p < 0.05). After the toxin injection, all groups treated with P. canaliculus extracts showed increased antioxidant effects on hepatocytes (p < 0.05). The lipid extracts induced antioxidant effects to protect the kidney by increasing lipid peroxidation (p < 0.05) and catalase activities (p < 0.05). Also, protein extracts showed antioxidant effects by increasing glutathione and catalase levels significantly (p < 0.005). In conclusion, P. canaliculus extracts, especially lipids and proteins, have potent antioxidant activities that protect vital organs from oxidation stress.

Differential Response in Ethanol Behaviors of Female Rats Given Various Weight Loss Surgeries.

AIMS: Currently, the only effective treatment for morbid obesity and its comorbidities is weight loss surgery (WLS). Growing evidence suggests that different types of WLS, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), have differential effects on alcohol consumption in humans and rats. Thus, we aimed to directly compare the effects of these two surgical procedures, for the first time in female rats, and to determine whether presence or absence of the ghrelin-producing stomach tissue has critical influence on postoperative alcohol intake. METHODS: We performed two experiments using an identical behavioral protocol, a continuous-access two-bottle choice protocol for various concentrations of ethanol (EtOH). In Experiment 1, 23 high fat diet (HFD) obese, female rats were randomized to three groups: RYGB, SG or sham-operated food-restricted (Sham) controls. In Experiment 2, HFD obese female rats received either sham (n = 11) or a modified RYGB surgery where the remnant stomach was removed (RYGB-X; n = 12). RESULTS: SG rats drank significantly less than RYGB for 4, 6 and 8% and significantly less than Sham for 6, 8 and 8% reinstatement. RYGB-X consumed significantly less EtOH than Sham across all concentrations, reaching significance for 6 and 8% reinstatement. CONCLUSION: These findings confirm reduced EtOH consumption by female SG rats as opposed to increased intake following RYGB, and provide the first experimental evidence that the remnant stomach in the RYGB procedure is contributory. Future studies in rats and humans are warranted to confirm that ghrelin plays a critical role in susceptibility to AUD development following WLS.