Celastrol and thymoquinone alleviate aluminum chloride-induced neurotoxicity: behavioral psychomotor performance, neurotransmitter level and oxidative-inflammatory burden in brain of rats

The exposure to metal aluminum such as aluminum chloride (AlCl3) induces inflammatory-oxidative reactions with progressive neurodegeneration in different brain regions in animal models. The current study was designed to assess the role of celastrol or thymoquinone (TQ) in alleviating AlCl3 induced behavioral psychomotor changes and oxidative-inflammatory burden in albino male rats. Four groups were used in this study, (i) vehicle control group, (ii) AlCL3 control group: rats received intraperitoneal injection (i.p.) of AlCl3 (10 mg/kg), (iii) AlCl3+TQ (10 mg/kg, i.p.) group and (iv) AlCl3+celastrol (1 mg/kg, i.p.) group. In general, all injections remained for 6 weeks. Behavioral psychomotor evaluation (open field test, rotarod test and forced Swimming test) were done to assess locomotor, motor coordination, anxiety-like behavior and depressive-like behavioral. Markers of oxidative stress, malondialdehyde (MDA), total antioxidant capacity (TAC) and catalase enzyme activity (CAT) and the proinflammatory mediators, tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) were measured in the rat brains. Neurotransmitters including acetylcholine (ACh), dopamine and serotonin in addition to acetylcholinesterase enzyme (AChE) level were measured in brain homogenates. Our results demonstrated that daily injection of TQ or celastrol significantly improved behavior psychomotor deficits, decreased AChE activity towards their normal levels. Tissue oxidative stress and proinflammatory markers were modulated by TQ and celastrol. These results concluded that TQ and celastrol have useful in alleviating AlCl3-induced neurotoxicity by their antioxidant and anti-inflammatory properties. Hence, they are looking promising for investigating their preventive effect in animal models of neurodegenerative diseases.

Automated Bolus Calculators and Connected Insulin Pens: A Smart Combination for Multiple Daily Injection Insulin Therapy

Although automated bolus calculators (ABCs) have become a mainstay in insulin pump therapy, they have not achieved similar levels of adoption by persons with diabetes (PWD) using multiple daily injections of insulin (MDI). Only a small number of blood glucose meters (BGMs) have incorporated ABC functionality and the proliferation of unregulated ABC smartphone apps raised safety concerns and eventually led to Food and Drug Administration (FDA)–mandated regulatory oversight for these types of apps. With the recent introduction of smartphone-connected insulin pens, manufacturer-supported companion ABC apps may offer an ideal solution for PWD and health care professionals that reduces errors of mental math when calculating bolus insulin dosing, increases the quality of diabetes data reporting, and improves glycemic outcomes.

A Fuzzy Method to Quantitatively Evaluate the Effect of Foam Deliquification in Gas Wells

Deliquification is the primary technique for stabilizing gas production and improving gas recovery in gas fields producing water, and foam deliquification is the key subject of research for the purpose of enhancing gas production and cutting down cost. However, there is no systematic method to evaluate and compare the effects of foam deliquification in gas wells in various conditions. Aiming at the above problem, a new fuzzy quantitative evaluation method for foam deliquification is proposed. The method focus on four indicators, namely, rate of change in daily gas production, rate of change in daily water production, rate of change in the difference between tubing and casing pressures, and rate of change in daily injection cost. The evaluation results are calculated by the linear analysis, hierarchy analysis and fuzzy relation synthesis operator. The method has been applied to 30 foam deliquification wells in Sulige gas field and Chongqing gas field, and the comprehensive index of foam deliquification effect is calculated. The advantage of this method is that the technical and economic factors affecting foam deliquifiction, the membership relationships of various indicators, as well as the weight coefficients of the indicators are integratedly considered. It can be used for comprehensive evaluation and quantitative comparison of foam deliquification effects in gas wells in various conditions, assisting in determining candidate wells for foam deliquification, and guiding the selection of foaming agents.

Advanced Hydrogels for the Controlled Delivery of Insulin

Insulin is a peptide hormone that is key to regulating physiological glucose levels. Its molecular size and susceptibility to conformational change under physiological pH make it challenging to orally administer insulin in diabetes. The most effective route for insulin delivery remains daily injection. Unfortunately, this results in poor patient compliance and increasing the risk of micro- and macro-vascular complications and thus rising morbidity and mortality rates in diabetics. The use of 3D hydrogels has been used with much interest for various biomedical applications. Hydrogels can mimic the extracellular matrix (ECM) and retain large quantities of water with tunable properties, which renders them suitable for administering a wide range of sensitive therapeutics. Several studies have demonstrated the fixation of insulin within the structural mesh of hydrogels as a bio-scaffold for the controlled delivery of insulin. This review provides a concise incursion into recent developments for the safe and effective controlled delivery of insulin using advanced hydrogel platforms with a special focus on sustained release injectable formulations. Various hydrogel platforms in terms of their methods of synthesis, properties, and unique features such as stimuli responsiveness for the treatment of Type 1 diabetes mellitus are critically appraised. Key criteria for classifying hydrogels are also outlined together with future trends in the field.

1215. A Mixed Methods Study on Severe Bacterial Infections in People Who Inject Drugs

Background Severe bacterial infections (SBI) associated with intravenous drug use have been increasing in frequency in the U.S. over the last decade. This mixed methods study aims to identify the risk factors associated with SBI in hospitalized individuals with recent injection drug use. Methods We conducted 34 quantitative and 15 qualitative interviews between August 2020 and June 2021 at Bellevue Hospital in New York City. Eligible participants were (1) >/= 18 year of age, (2) admitted with a SBI, and (3) reported injection drug use within the 90 days prior to admission. Quantitative and qualitative data was obtained using a quantitative survey and in-depth, semi structured interviews of participants respectively. Analysis was performed to examine trends and explore common themes potentially contributing factors to SBI. Results Of the 34 participants included, the median age was 37.5, 85% were male, 53% white, and 65% reported being homeless within the past 3 months. Endocarditis was the most common primary diagnosis (65%). Median length of hospital stay was 24 days and 35% required ICU level care during admission. A causative microorganism was identified in 85% of participants and 50% had Staphylococcus aureus as the sole organism. Discharges against medical advice occurred in 35%. Daily injection drug use in prior 30 days was 95% with a median of 10 injections per day. In the 30 days prior to admission, 50% reported an increase in injection frequency, 80% reported reusing needles and/or syringes, 75% reused cookers, 65% reused cottons. Analysis of qualitative interview data revealed high risk injection behaviors. Participants were not practicing and unaware of strategies to reduce their risk of drug injection-related SBI. Prior hospitalizations for SBI did not impact on this knowledge deficit on what constitutes bacterial infection risk and how to prevent it. Conclusion Study findings highlight the complexity of the injection drug use process and the potential social and physiological pathways leading to SBI. Multiple domains at the structural, network, and individual level that impact drug injection practices and provide context by which these factors predispose and lead to physiological tissue damage and the development of SBI among PWID. Disclosures Benjamin Eckhardt, MD, MS, Gilead Sciences (Grant/Research Support)

Therapeutic effects of silver nanoparticle and L-carnitine on aerobic vaginitis in mice: an experimental study

Introduction: Aerobic vaginitis (AV) is a type of vaginal infection that occurs at the reproductive age of women. In this study, we aimed to study the possible anti-AV therapeutic effects of silver nanoparticles (AgNPs) and L-carnitine (LC) in the mouse model. Methods: AV model was established by intra-vaginal inoculation of 108 CFU/mL Staphylococcus aureus and Escherichia coli (1:1) in adult NMRI mice. Susceptibilities of the bacteria were examined against AgNPs by inhibitory concentration (IC-50 and IC-90) and minimum biofilm inhibitory concentration (MBIC- 90) methods. The regimens therapy was intra-vaginal inoculation of AgNPs at MBIC- 90 and a daily injection of 250 mg/kg LC for two weeks. Mice were classified into healthy (control) and AV groups and then treated by LC, AgNPs, and AgNPs + LC. The vaginal smears were taken daily and tissue sections were prepared using the hematoxylin and eosin (H & E) method. Results: Minimum inhibitory concentrations (MICs) of AgNPs for E. coli, S. aureus, and their mixture were 250, 125, and 500 ppm, and their MBIC-90% were 500, 250, and 1000 ppm, respectively. The estrus cycle of mice treated with co-administration of AgNPs and LC was similar to the control group (P < 0.05). The results of histology also showed that infected mice were treated with AgNPs and LC, simultaneously. Conclusion: Single bacteria are more sensitive than their mixed model to these NPs. Co-administration of AgNPs as an antibacterial agent and LC as an antioxidant agent can treat AV in the infected mice.

The concurrent therapeutic potential of adipose-derived mesenchymal stem cells on Gentamycin-induced hepatorenal toxicity in rats

Background: Adipose mesenchymal stem cells (AMSCs) are a type of stem cell employed to repair damaged organs. This study aimed to see how effective AMSCs are at treating gentamycin-induced hepatorenal damage in rats. Methods: 18 male Wister rats were assigned into three groups; control, Gentamycin (GM), and GM+AMSCs. GM induced hepatorenal toxicity through daily injection (100 mg/kg, i.p.) for eight days. On day 9, AMSC (106 cells/ml/rat) was injected intravenously. Results : Creatinine, urea, uric acid, AST, ALP, ALT, TNF-, and MDA levels decreased, whereas IL-10, GSH, and CAT levels increased, indicating the therapeutic potency of intravenous injection AMSCs. Conclusion: The current study demonstrated the simultaneous therapeutic efficacy of adipose mesenchymal stem cells on the liver and kidney in the treatment of Gentamycin-induced hepatotoxicity. These data show that AMSCs could be a feasible therapy option for liver and kidney disease.

Ovarian Folliculogenesis and Uterine Endometrial Receptivity after Intermittent Vaginal Injection of Recombinant Human Follicle-Stimulating Hormone in Infertile Women Receiving In Vitro Fertilization and in Immature Female Rats

The uterine first-pass effect occurs when drugs are delivered vaginally. However, the effect of vaginally administered recombinant human follicle-stimulating hormone (rhFSH) on ovarian folliculogenesis and endometrial receptivity is not well established. We aimed to compare the efficacy of rhFSH administered vaginally and abdominally in clinical in vitro fertilization (IVF) treatment, pharmacokinetic study, and animal study. In IVF treatment, the number of oocytes retrieved, endometrial thickness and uterine artery blood perfusion were not different between women who received the rhFSH either vaginally or abdominally. For serum pharmacokinetic parameters, significantly lower Tmax, clearance, and higher AUC and T1/2_elimination of rhFSH were observed in women who received rhFSH vaginally, but urine parameters were not different. Immature female rats that received daily abdominal or vaginal injections (1 IU twice daily for 4 days) or intermittent vaginal injections (4 IU every other day for two doses) of rhFSH had more total follicles than the control group. In addition, the serum progesterone and progesterone receptors in the local endometrium were significantly higher in the groups treated with intermittent abdominal or vaginal injection of rhFSH, compared with those who recieved daily injection. In summary, vaginal administration of rhFSH may provide an alternative treatment regimen in women receiving IVF.

Which illicit drugs are injected in Oslo? A study based on analysis of drug residues in used injection equipment and self-reported information

Background People who inject drugs (PWID) have a high risk of premature death due to fatal overdoses. Newly emerged fentanyls, much more potent than heroin and other opioids, may increase this risk further. Therefore, precise information on injected drugs is critical to improving prevention strategies. Aims This study aimed to analyse drug residues in used injection equipment in order to determine drug and drug combinations and compare and complement findings with self-reported information. Methods Used syringes and needles ( n=766) were collected at the supervised drug consumption facilities, the needle exchange service and two low-threshold health services for problem drug users in Oslo, Norway. The material was collected every third month from June 2019 to June 2020 and analysed for 64 substances using highly specific analytical methods (ultra–high performance liquid chromatography tandem mass spectrometry). Additionally, a street-recruited sample of PWID was interviewed from 2017 to 2019 regarding their drug injection habits ( n=572). Results Heroin (65.5%) or amphetamines (59.8%), often in combination (30.5%), were commonly detected in drug residues. Other opioids, stimulants or benzodiazepines were rarely detected (6.1%). Fentanyl was detected in only one syringe. Heroin was the most reported drug (77.6% during the past four weeks, 48.3% daily/almost daily), followed by amphetamines (57.5% during the past four weeks, 23.1% daily or almost daily). Injection of methadone, buprenorphine and dissolved tablets was self-reported more frequently than determined in drug residue findings. Conclusions Analysis of the injection equipment proved useful as a non-invasive, rapid and accurate means to obtain detailed information on injected drugs in Oslo and supplement traditional PWID survey information.