Injection Of Acetate Research Articles

The Combined Application of Bleomycin and Triamcinolone for Treating Refractory Keloids.

Triamcinolone acetate injections are considered the first treatment option for keloids, but quite high proportions of keloids either do not respond to triamcinolone or develop recurrence. Beneficial effects of intralesional bleomycin have been recently shown in the treatment of keloids and hypertrophic scars. However, the efficacy of combination therapy using intralesional triamcinolone and bleomycin remains undetermined. The purpose of this study was to evaluate the efficacy of using bleomycin and triamcinolone mixture to treat refractory keloids. In total, 33 patients with resistant keloids (including 8 men and 25 women) and a mean age of 36.52 years (age range of 18-65 years) were enrolled in this study. A mixture of bleomycin (1 u/cc) with triamcinolone acetonide (13.3 mg/cc) was injected intralesionally into the keloids every 4 to 6 weeks for a maximum of 6 cycles. The clinical improvement was evaluated using the Japan Scar Scale (JSS) and the physician's global assessment of the flattening of the lesions. Side effects were also noted and recorded. In all patients, the total JSS scores decreased significantly after treatment (2.33 ± 1.05), compared with baseline (11.61 ± 2.59), ( p < .001); 26 keloids (78.8%) showed an excellent response (75%-100% flattening), 7 keloids (21.2%) showed a fair response (25%-75% flattening), and 0 keloids (0%) showed a poor response (<25% flattening). Observed side effects were ulceration (33.3%), hyperpigmentation (33.3%), hypopigmentation (15.15%), secondary infection (33.3%), and telangiectasis (15.15%). The combined use of bleomycin and triamcinolone offers a promising treatment option for individuals who have not responded well to traditional therapies.

Effects of Combined Laparoscopic Cystectomy and Leuprolide Acetate Therapy on Anti-Mullerian Hormone Level and Antral Follicle Count Profile in Endometriosis

Objective: This study examines the effectiveness of combined laparoscopic cystectomy and leuprolide acetate therapy on AMH level and AFC profile in endometriosis. Method: This study is a randomized controlled clinical trial with open label form. The subjects were divided into control and therapy groups, with the therapy group receiving leuprolide acetate injection following laparoscopic cystectomy. In both groups, the AMH levels and AFC were examined prior to the surgery and six weeks after before they were compared. Results: There were significant pre-post differences of AMH levels(p = 0.000) and AFC (p = 0.000) in the therapy group but not in the control group. In the therapy group, the mean increases of AMH level and AFC were 0.94 (95% CI: 0.63-1.25) and 9.53 (95% CI: 6.83-12.24), respectively. Linear regression model found that AFC level prior to intervention was a significant predictor of endometriosis ASRM grade (p = 0.001) with an R-value of 0.633, suggesting strong correlation. Conclusion: The combined therapy of laparoscopic cystectomy and leuprolide acetate injection for endometriosis provided better outcome concerning ovarian reserve, as opposed to the therapy with laparoscopic cystectomy alone.

Physiological and behavioral effects of hormonal contraceptive treatment in captive, pair-bonded primates (Plecturocebus cupreus).

Hormonal contraception is an effective, reversible tool for managing birth rates in humans and nonhuman animals alike. However, manipulating reproductive hormones has behavioral consequences that can impact social and sexual behavior between conspecifics. First, we studied 18 pairs of nonreproductive titi monkeys (Plecturocebus cupreus) to test the efficacy of a novel method of hormonal contraception (deslorelin acetate implants) on reproductive hormone cycling in females and found significant reductions in urinary estrogens and progestagens among treated females compared to untreated controls. We then studied 35 nonreproductive pairs of coppery titi monkeys (Plecturocebus cupreus) to ascertain whether treating females with one of 2 different forms of hormonal contraception (deslorelin acetate implants (n = 17) or medroxyprogesterone acetate injections (n = 9)) would influence the relationship between pair mates compared to the relationship between untreated females and their vasectomized male mates (n = 9). Over a 5-month period, we found no differences in affiliative behaviors between pairs containing untreated females compared to pairs in which the female was treated with either deslorelin acetate or medroxyprogesterone acetate. Similarly, we found no differences in affiliation between pairs in the 2 treatment groups. This study is the first to examine behavioral consequences of hormonal contraception in a pair-bonding species. The results are encouraging for captive, managed breeding colonies of such social animals, especially those used in behavioral research.

Comparison of triamcinolone and methylprednisolone efficacy and steroid flare reaction rates after shoulder corticosteroid injection: a prospective interrupted time series study.

A corticosteroid flare reaction is a well-described phenomenon that causes significant pain and dysfunction. The paucity of literature impedes decision making regarding which corticosteroid to use for shoulder injection. The purpose of this study was to compare methylprednisolone acetate (MPA) and triamcinolone acetonide (TA) injections in the glenohumeral joint and/or subacromial space in terms of efficacy and the incidence of steroid flare reactions. In this prospective, interrupted time series, parallel study, patients received injections in the glenohumeral joint and/or subacromial space. MPA and TA were used during 2 discrete 3-month periods. The injections consisted of 2 mL of lidocaine, 2 mL of bupivacaine, and 80 mg of either MPA or TA. Visual analog scale (VAS) pain scores were recorded immediately before injection; 1-7 days after injection; and 3, 6, and 12 months after injection. The primary outcome was the incidence of a steroid flare reaction, defined as a post-injection increase in the VAS score by ≥2 points. The secondary outcome was injection failure, defined as a post-injection VAS score greater than the baseline score or the need for another intervention. We used linear mixed models with a patient-level random intercept to identify the mean VAS score change for TA injections in the first week after injection. MPA or TA shoulder injections were administered in 421 patients; of these patients, 15 received bilateral-joint injections whereas 406 received a single-joint injection, for a total of 436 injections (209 MPA and 227 TA injections). Pain scores in the first week after injection were available for 193 MPA and 199 TA injections. Significantly more patients in the MPA cohort reported flare reactions compared with the TA cohort (22.8% vs. 4.0%, P<.001) during the first week after injection. In the first week after injection, the mean VAS score of patients receiving TA injections was 1.05 (95% confidence interval, 0.47-1.63) lower than that of patients receiving MPA injections when adjusted for age, sex, race, pain type, surgeon type, and injection site. At 3 months, surveys for 169 MPA and 172 TA injections were completed, with no significant difference in the rate of injection failure for MPA vs. TA (42.6% vs. 36.1%, P=.224). Treatment failure rates were significantly higher for MPA than for TA at 6 months (78.44% vs. 62.5%, P<.001) but not at 12 months (81.18% vs. 81.42%, P=.531.) CONCLUSION: TA injections resulted in a >5-fold reduction in steroid flare reactions, with statistically superior 6-month efficacy rates, compared with MPA injections. This study supports TA as a more viable corticosteroid option for shoulder injection.

Periprosthetic Joint Infection Risk After Primary Total Knee Arthroplasty: Are All Preoperative Corticosteroid Injections the Same?

BackgroundPrevious evidence has demonstrated an increased risk of periprosthetic joint infection (PJI) following primary total knee arthroplasty (TKA) in patients receiving corticosteroid injection (CSI) within 3 months of surgery. The study aimed to determine if PJI risk after TKA varied among different corticosteroid agents. MethodsA total of 85,073 patients undergoing primary TKA from 2009 to 2019 were identified from a large national database. Of these, 1,092 (1.3%) received an ipsilateral, intra-articular CSI within 90 days of TKA. These patients were compared to those not receiving CSI using multivariate logistic regressions following 1:4 propensity score matching, with PJI development as the primary outcome. ResultsPatients given an injection of any corticosteroid within 90 days of TKA had significantly higher PJI rates compared to controls (1.6 versus 0.41%; P < .001). This finding was driven by patients receiving methylprednisolone acetate (n = 543) or betamethasone (n = 153), with prevalence rates of 1.7 and 2.6%, respectively (P = .003 and P = .01, respectively). No significant increase in the rate of PJI was observed for patients receiving triamcinolone (1.2%; P = .08; n = 342) or dexamethasone (0.0%; P = 1; n = 54) within 90 days preceding TKA. PJI risk for all agents, administered more than 90 days preoperatively normalized to control levels (0.51 versus 0.34%). ConclusionsThese results suggest that PJI risk varies with CSI type. In this large database study, only patients given methylprednisolone acetate or betamethasone injections within 90 days of surgery had significantly higher PJI rates compared to controls.

Expression of Ki67 and CD68+ cells of red bone marrow monocyte sprout under triptorelin administration in the hypothalamic-pituitary-testis regulatory system: the experimental study

Background. Red bone marrow (RBM) is the main organ of human haemopoiesis. Monocytopoiesis plays an important role in the formation of transitional states: from normal to pathology and in the transformation of pathological processes from one stage to another. In modern urological practice, the substance triptorelin is widely used for androgen deprivation therapy, according to the recommendations of the European Association of Urology. Ki67, a commercially available monoclonal antibody that reacts with a nuclear antigen detected only in proliferating cells, is used to assess immunohistochemical changes. CD68 is a valuable cytochemical marker for immunostaining of monocytes/macrophages during histochemical analysis of tissues in inflammation, cancer and other immunohistopathological purposes. The purpose of the study is to evaluate the proliferative activity and differentiation of progenitor cells through the expression of Ki67 and CD68+ monocyte sprouting of RBM under chemical castration of central origin in male rats caused by the administration of triptorelin solution with quercetin addition to the diet for one year. Materials and methods. The study was conducted on 60 adult male white rats. They were divided into 3 groups: group I — control (n = 10), group II (n = 25) — subcutaneous injection of triptorelin, group III (n = 25) — subcutaneous injection of triptorelin acetate and quercetin. Immunohistochemical analysis of biopsy specimens was conducted following a standard protocol at the Department of Pathological Anatomy in Sumy State University, under the supervision of the Head of the Department, Prof. Romaniuk A.M. Results. The study evaluated Ki67 expression on microsections of rat red bone marrow through immunohistochemistry, which exclusively reacted with nuclear antigen in the monocyte sprout’s proliferating cells. Irregular changes were revealed depending on the experimental groups and time periods. Immunohistochemical analysis of RBM tissue using anti-CD68 antibodies in the experimental groups revealed a strong positive cytoplasmic response in monocytes and resident macrophages located in the monocyte sprout and surrounding environment. The data of the two experimental groups of RBM had a noticeable proliferating compartment, as evidenced by the high content of mitotically active DNA in them. These data correspond to the results obtained in the experiment with triptorelin, where we found a marked positivity of Ki67, depending on the timing of the experiment and the addition of the flavonoid quercetin. This discrepancy suggests that bone marrow cells that grow and proliferate under normal conditions are guided by natural control mechanisms and may lose their Ki67 expression after leaving the progenitor compartment and entering the differentiation compartment. Conclusions. Triptorelin administration induces hormonal imbalance in the hypothalamus-pituitary-testis-RBM system, resulting in quantitative and qualitative alterations in the cells of the RBM monocytic lineage. The level of cell proliferation, as measured by Ki67, is highest during the third month of observation. Cytoplasmic expression of CD68 is evident in two experimental groups from the third to the sixth month, suggesting activation of immunoreactive cells as they migrate from the progenitor compartment to the differentiation compartment.

Field evaluation of carbon injection method for in-situ biological denitrification in groundwater using geochemical and metataxonomic analyses

This study focuses on the bioremediation of nitrate-contaminated groundwater, which has become a significant environmental problem due to the increasing usage of fertilizers and sewage disposal. The nitrate reduction efficiencies of biological denitrification by injection of carbon source in a pilot-scale treatment system setup were investigated at a groundwater contamination site. The field test was conducted using acetate as a carbon source for 22 days to assess the nitrate reduction efficiencies of in-situ treatment. Geochemical parameters and microbial community analysis using next-generation sequencing were performed before and after carbon source injection. After 12 h of reaction time, nitrate concentration decreased from 31.6 to 4.2 mg-N/L at PC-2, and then remained stable at 3.9 mg-N/L. The nitrate reduction rate when acetate was injected was 29.0 mg-N/L/day. Aquabacterium commune, pseudomonas brassicacearum, dechloromonas denitrificans, and Massilia FAOS were dominant species after acetate injection. Predictive metabolic pathway analysis indicated that nitrate reduction metabolisms during injection of acetate were denitrification and assimilatory nitrate reduction to ammonium. The evaluated hazard quotient of nitrate-contaminated groundwater significantly decreased after acetate injection (non-carcinogenic risk decreased from 1.176 to 0.134 for children). This research could provide fundamental information for decision-makers in nitrate-contaminated groundwater quality protection and management.

FRI312 Diplopia And Headache After Treatment With GnRH Agonist

Abstract Disclosure: A.A. Zakkar: None. M. Al Mushref: None. M. Fadanelli: None. Case Report: The Patient is a 46-year-old male with past medical history of hypertension and prostate cancer, currently undergoing treatment with leuprolide acetate injections, who presented to the emergency department with a complaint of worsening headache. He received his second injection 3 days prior to admission and within hours he developed a headache in the frontal area that was continuous and worsening over time, increasing with positional changes of his head. One day after the treatment he developed persistent double vision. The patient reported that he has had worsening vision over the last year and was to see an ophthalmologist but was diagnosed with prostate cancer at the same time so he became more focused on the oncologic care. He also reported poor balance, excessive thirst and increased urination of large volumes of urine every hour with nocturia several times. On exam the vital signs were normal, he was A&amp;Ox4 and in no distress. He had left abducens and oculomotor nerve palsy but an otherwise benign exam. MRI of the brain revealed a sellar mass measuring 2.2 x 1.7 x 2.3 cm consistent with pituitary macroadenoma extending into the suprasellar cistern, compressing the pituitary stalk and the optic chiasm. Patient was evaluated by ophthalmology who noted +2 optic nerve edema of the left eye. Laboratory evaluation revealed low ACTH of 6 pg/mL at 5:30AM along with corresponding cortisol level of only 1.6 mcg/dL. FSH was low and LH undetectable as expected with GnRH agonist therapy. Growth hormone level, IGF-1, l and prolactin levels were all normal. The TSH was 0.50 microunits/mL with a freeT4 of 1.0. Urinalysis revealed dilute urine with specific gravity &amp;lt;1.006. Serum sodium on admission was 137 mmol/L and after overnight fasting was 140 mmol/L. The patient was started on desmopressin 0.1 mg po at bedtime and on intravenous dexamethasone 4 mg q6hrs. He was evaluated by neurosurgery and ENT who recommended trans-sphenoidal resection of the mass. Pathology report of the specimen was consistent with a pituitary adenoma with infarction without hemorrhage. The patient reported an improvement in his left eye vision and lateral rectus palsy. He was transitioned to oral hydrocortisone 20 mg daily and 10 mg every afternoon prior to discharge. On follow up with endocrinology several months later he was found to have persistent adrenal insufficiency and developed central hypothyroidism that required treatment. Conclusion: Patients with an undiagnosed pituitary adenoma are at risk of tumor expansion and mass effect as well as pituitary apoplexy during treatment with GnRH agonists. In our case clinical presentation was consistent with pituitary apoplexy without evidence of pituitary hemorrhage soon after GnRH agonist. A full ophthalmologic exam may be an appropriate screening prior to initiation of such therapy. Presentation: Friday, June 16, 2023

Comparative Study of Combination of Intralesional Triamcinolone Acetate with 5-Fluorouracil Versus Triamcinolone Alone in Treatment of Keloid

Objectives To assess various parameters of outcomes in the management of keloid by comparing the combination of 5-Fluorouracil (5-FU) with triamcinolone acetate and triamcinolone alone. Materials and Methods The present study was carried out as a prospective comparative study over a period of 24 months. A total of 70 diagnosed Keloids patients were included in the study, who were randomly divided into two equal groups: 35 patients were administered triamcinolone acetate and 5-FU (0.1 mL TA + 0.9 mL 5-FU) were classified as Group A (Triamcinolone acetonide [TAC] + 5-FU) while the remaining 35 (50.0%) patients were administered a 1 mL intralesional injection of triamcinolone acetate alone and were classified as Group B (TAC alone). Patients of both groups were administered the injections selected for them at a 3 week interval for 3–6 months. Patients and independent observers assessed the scar at each visit until the last follow-up. Assessment by patients was done for pain, itching, scar colour, stiffness, thickness and irregularity of the keloid on a 10-point scale, with higher values showing worse results. Assessment of scars by an independent observer was done on a similar scale, including vascularization, pigmentation, thickness and pliability. Results Initially vascularity, scar colour, vascularity and thickness of patients’ scars in both the groups assessed by the patient as well as the observer were comparable, which remained comparable up to the administration of the second dose. Thereafter, both patient and observer observed that the parameters of TAC + 5-FU administered patients were significantly lower than of those administered TAC alone. Assessment of irregularity in shape and pliability of scar was done only by the patient. Initially both irregularity and pliability of the patients in both groups were comparable, which remained comparable up to the administration of the third dose. Thereafter, the parameters of TAC + 5-FU administered patients were significantly lower than those administered TAC alone. Conclusion The findings in this study indicate that adjuvant 5-FU to TAC was more effective as compared to TAC alone.

Multiple ammonia-induced episodes of hepatic encephalopathy provoke neuronal cell loss in bile-duct ligated rats

Hepatic encephalopathy (HE) is defined as a reversible syndrome and therefore should resolve following liver transplantation (LT). However, neurological complications have been reported in up to 47% of LT recipients, which have been documented to be associated with a history of overt HE pre-LT. We hypothesise that multiple episodes of HE lead to permanent cell injury and exacerbate neurological dysfunction. Our goal was to evaluate the impact of cumulative HE episodes on neurological status and brain integrity in rats with chronic liver disease. Episodes of overt HE (loss of righting reflex) were induced following injection of ammonium acetate in bile duct ligation (BDL) rats (BDL-Ammonia) every 4 days starting at week 3 post-BDL. Neurobehaviour was evaluated after the last episode. Upon sacrifice, plasma ammonia, systemic oxidative stress, and inflammation markers were assessed. Neuronal markers including neuron-specific nuclear antigen and SMI311 (anti-neurofilament marker) and apoptotic markers (cleaved caspase-3, Bax, and Bcl2) were measured. Total antioxidant capacity, oxidative stress marker (4-hydroxynonenal), and proinflammatory cytokines (tumour necrosis factor-alpha and interleukin-1β) were measured in brain (hippocampus, frontal cortex, and cerebellum). Proteomic analysis was conducted in the hippocampus. In hippocampus of BDL-Ammonia rats, cleaved caspase-3 and Bax/Bcl2 ratio were significantly increased, whereas NeuN and SMI311 were significantly decreased compared with BDL-Vehicle rats. Higher levels of oxidative stress-induced post-translational modified proteins were found in hippocampus of BDL-Ammonia group which were associated with a lower total antioxidant capacity. Ammonia-induced episodes of overt HE caused neuronal cell injury/death in BDL rats. These results suggest that multiple bouts of HE can be detrimental on the integrity of the brain, translating to irreversibility and hence neurological complications post-LT. Hepatic encephalopathy (HE) is defined as a reversible neuropsychiatric syndrome resolving following liver transplantation (LT); however, ∼47% of patients demonstrate neurological impairments after LT, which are associated with a previous history of overt HE pre-LT. Our study indicates that multiple episodes of overt HE can cause permanent neuronal damage which may lead to neurological complications after LT. Nevertheless, preventing the occurrence of overt HE episodes is critical for reducing the risk of irreversible neuronal injury in patients with cirrhosis.

Effects of leonardite and lignite on blood parameters in rats exposed to lead acetate

The study aimed to research in vivo changes in the hematological and biochemical parameters of laboratory rats' blood when they were continuously exposed to a moderate dose of lead acetate while receiving humic feed additives made of leonardite and lignite. Two-month-old white rats were used to assess the detoxifying properties of the humic compounds leonardite and lignite. The analog pair approach was used to create four groups of eight animals from 32 male laboratory rats for the study. Rats received a pre-meal injection of lead acetate at a dose of 7 mg/100 g of animal weight (1/110 LD50) using a veterinary feeding needle. By creating solutions from lignite and leonardite at a dosage of 18 and 25 mg/kg depending on the active ingredient, humic feed additives were supplied to animals. It has been demonstrated that lignite- and leonardite-based feed additives may affect the morphological parameters of lead acetate-treated rats' blood, including hemoglobin, hematocrit, erythrocyte, and platelet count. These parameters were very near to the levels of the intact rats, which suggests that these humic feed additives may have an anti-anemic impact. The effects of feed additives from leonardite and lignite on laboratory rats in groups that were also exposed to a toxic agent for all 21 days of the experiment led to the normalization of markers of the state of protein metabolism in the group of intact animals (serum protein, albumins, urea, creatinine), particularly activity of the enzyme’s aspartate aminotransferase and alanine aminotransferase. As one of the most crucial indicators of lipid metabolism together with cholesterol, the concentration of triglycerides was slightly lower in the humic substances treated groups than in the intact animals. It was discovered that using a feed supplement made from leonardite in a dosage of 18 mg/kg, which contained more fulvic acids than lignite, led to more favorable blood test results in the research group.

Pharmacological effect of Argyrolobium roseum (Camb.) Jaub & Spach extracts against lead-induced toxicity in rats.

Argyrolobium roseum (Camb.) Jaub & Spach (Papilionaceae) is a medicinal plant, cultivated in northern areas of Pakistan. The consumption of trace minerals (lead) is very toxic to the vital organs of the body, therefore the overcome of these minerals is very necessary. In this regard, this study aimed to assess the potential pharmacological effect of aqueous and ethanolic extract of Argyrolobium roseum (Camb.) Jaub & Spach against pb-induced oxidative stress, histological changes in Pb-induced rats' liver and kidney, and anti-inflammatory effect. The metal concentrations in liver and kidney homogenates were measured through atomic absorption spectrophotometer. The antioxidant activity was measured through DPPH and FRAP assay. Pb concentrations were significantly higher in liver and kidney homogenates after injection of Pb acetate was given intraperitoneally (45.2 ± 6.8 and 58.8 ± 7.9, respectively; p < .0001). The level of Pb in liver and kidney homogenates was significantly reduced by aqueous and ethanolic extracts of Argyrolobium roseum (Camb.) Jaub & Spach. The Pb + Aq-600 mg/kg-treated rats exhibited a protective effect on hepatocytes cells against Pb-induced liver injury and restored the cells of the kidney. Pb + Aq-600 mg/kg showed higher antioxidant activity as compared to other treated groups. The highest decreased MDA level was found in liver and kidney homogenate of Pb + Aq-600 mg/kg rats (11.2 ± 1.51 nmol/mg; p < .001) and GSH and CAT levels tended to normal after treatment of Pb + Aq-600 mg/kg in rats. The ALAD, ALT, AST, and ALP level were enhanced and tended to be normal after the Aq-400 and Aq-600 mg/kg treatment in Pb-exposed rats. The result showed that 600 mg/kg Aq + Pb exhibited significant (p < .001) anti-inflammatory activity. The findings of this study concluded that treatment of the aqueous extract of Argyrolobium roseum (Camb.) Jaub & Spach reduces the renal and hepatic damage in Pb-induced rats and it also decreases oxidative stress via improving antioxidant components.

EDUKASI ANIMASI KANKER SERVIKS MENINGKATKAN MINAT WANITA USIA SUBUR TERHADAP PEMERIKSAAN IVA

The low achievement of the target of the visual acid acetate injection examination (IVA) suggests that women of fertile age (WUS) still get little education about cervical cancer. The use of pocketbook media did not show the achievement of IVA inspection targets. The aims to know the impact of cervical cancer animation education on the increased interest of WUS in conducting IVA examinations in Puskesmas Pal Lima. The Method is quasi-experimental research was carried out from April to May 2022 in the UPT Puskesmas Pal Lima work area. The large sample for the research was 30 subjects obtained from the Lameshow formula. Interest scores before and after cervical cancer animation education were measured using a questionnaire of 20 questions. Data analysis using a pair-t test The results of this study showed that giving cervical cancer animation education increased WUS interest in IVA examinations (p = 0,007). The interest score increased by 6.37. Cervical cancer education using animated videos can be used as a midwife to increase WUS interest in IVA examination. Cervical cancer education with audiovisual animation is more efficiently accepted by society than pocket books.

1537-P: Regulation of Energy Balance by a Gut–Brain Axis Mediated by SCFAs and FFA2/3 in the Brain

Short-chain fatty acids (SCFAs) derived from gut microbiota fermentation have been shown to generate beneficial metabolic effects on energy and glucose homeostasis by binding with free fatty acid receptors 2 (FFA2) and 3 (FFA3). Accumulating evidence indicates that the gut microbiota/SCFAs interact with the central nervous system (CNS) to regulate central metabolic function. Interestingly, we found that a single bolus intracerebroventricular (ICV) injection of acetate (ACE), propionate (PRO), or butyrate (BUT) dose-dependently inhibited food intake in an FFA2/3-dependent manner. Notably, both in situ hybridization and RNAscope analysis showed that FFA3 but not FFA2 was expressed in the cerebellar granule neurons, which was inhibited by PRO or FFA3-selective agonists in a Gi/o-dependent mechanism. We also showed that high-fat diet (HFD)-induced hypothalamic inflammation is diminished by dietary fiber supplementation, which is associated with increased circulating SCFAs. Notably, these anti-inflammatory effects of dietary fiber supplementation were partially attenuated in FFA2/3 double-knockout mice, suggesting a beneficial effect of FFA2/3 on hypothalamic inflammation. Taking all these together, our results suggest a model that SCFAs act on the brain to regulate energy homeostasis and hypothalamic inflammation. Disclosure X.Yang: None. P.Xu: None. P.Luo: None. B.Feng: None. H.Ye: None. N.Antony: None. L.Carrillo-sáenz: None. V.C.Torres irizarry: None. B.T.Layden: Consultant; Bayer Inc. Y.He: None. Funding National Institutes of Health (R01DK123098, P30DK020595 to P.X.), (P20GM135002, R01DK129548 to Y.H.), (T32AA026577 to V.C.T.I.); American Heart Association (915789 to V.C.T.I.), (20POST35120600 to Y.H.); U.S. Department of Defense (W81XWH-20-1-0075 to P.X

#5852 EFFECT OF DIET ON THE COLLECTOR DUCT BEHAVIOUR: RELEVANCE IN PRECLINICAL DRUG DEVELOPMENT

Abstract Background and Aims Drug induced syndrome of inadequate antidiuretic hormone secretion (SIADH) is a common problem in clinical practice. Early detection of this side effect at a preclinical level would improve safety and efficiency. We investigate the role of different diets in preclinical detection of SIADH. Method Animals were divided into two groups (n = 4 each), one receiving standard pellet based diet, and the other one a diluted hyposodic gelified liquid diet. After one week, both groups were administered daily intraperitoneal (i.p.) injections of desmopressin acetate (ddAVP; 0.4 μg/kg) and a volume of distilled water equivalent to 2.5% of body weight for 7 days. Animals were placed in metabolic cages for 24h at the end of each period to collect and analyse the urine, and a blood sample from the tail vein was obtained. Weight, water and food intake were measured on a daily basis. Results Differences in water and electrolyte balance are shown in Table 1. Pellet fed animals presented an increased water intake and produced a more concentrated urine compared to those on a hyposodic diet. When analysed in detail, urinary osmolality was mainly driven by ionic osmoles in pellet fed animals (42,25 ± 4,72 vs 266,30 ± 17,32 mOsm/kg, p&amp;lt;0,005). Of note, there seems to be an occult osmole, especially prominent in the pellet group (osmol gap 20,40 ± 3,18 vs 99,89 ± 9,81 mOsm/kg, p = 0,017). All of the above suggest there is a net retention of water, sodium and potassium in those animals fed with a conventional pellet diet. Daily administration of ddAVP/water induced a mild transient hyponatremia that was recovered 24h later in both groups; this situation was repeated over a 7 day period. Pellet fed animals did not modify water intake, diuresis, free water clearance or urinary osmolality after ddAVP/water treatment, suggesting that hyperosmolar diets significantly increase urinary osmolality fixating urinary water losses and impairing further urinary concentration. On the contrary, animals on a hyposodic diet did present antiaquaresis, as shown by an increase in water intake, a decrease in diuresis and free water clearance and an increase in urinary osmolality. Animals fed with hyposodic diet progressively lost weight, while pellet fed animals did not. However, this trend was reversed after 4 days of treatment with ddAVP/water, again suggesting a degree of water retention. It is remarkable that we have found signs of water retention despite the fact that the induced hyponatremia is mild and transient. Conclusion The antiaquaretic effect of ddAVP is overridden by the amount of urinary osmoles excreted when on a pellet diet, which seem to fixate the amount of water in the urine. Therefore, the use of hyposodic diets in preclinical drug development is essential when SIADH is likely to be expected, as its effects will be unnoticed if a standard diet is used.

Effects of Intracerebroventricular Injection of the Steroidal and Non-Steroidal Anti-Inflammatory Drugs on the Seizures during the Estrous Cycle in Rat.

Because of the mutual relationship between neural inflammation and seizure, this study aimed to determine the effects of intracerebroventricular (ICV) injection of the steroidal and non-steroidal anti-inflammatory drugs on pentylenetetrazol (PTZ)-induced seizures during the estrous cycle in rats. A total of 105 adult female Wistar rats were selected and divided into seven groups, including the control (saline), ketorolac tris salt (7.5, 15, and 30 µg), and methylprednisolone acetate (0.15, 0.3, and 0.6 µg), each with four subgroups (proestrus, estrus, metestrus, and diestrus) and three replicates (n=5). After a week of acclimatization, the estrous phase determination and synchronization were performed. Acute epilepsy was inspired by the intraperitoneal injection of 80 mg/kg of PTZ 30 min after the ICV injection of ketorolac and methylprednisolone acetate. The initiation time of myoclonic seizures (ITMS), the initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were measured for 30 min. Data were shown as mean±SD and analyzed using One-way ANOVA followed by Tukey-Kramer multiple comparison post hoc test (P<0.05). According to the results, ketorolac (15 and 30 µg) and methylprednisolone acetate (0.3 and 0.6 µg) significantly increased the ITTS and ITMS but decreased SD during the estrous cycle, compared to the control (P<0.05). Moreover, MR and SD were significantly decreased by ketorolac (7.5, 15, and 30 µg) and methylprednisolone (0.3 and 0.6 µg), compared to the control during the estrous cycle (P<0.05). Therefore, it seems that both ketorolac and methylprednisolone possess dose-dependent anticonvulsant effects that may decrease neural inflammation.

Extended pilot test of a cross-injection in situ denitrification system for pre-emptive treatment of municipal well water

Elevated groundwater nitrate concentrations have been linked to deleterious health and environmental effects. A significant source of the nitrate is nitrogen fertilizers applied to agricultural landscapes. Beneficial Management Practices (BMPs), including the optimization of fertilizer use and selective crop rotations, have proven to be effective in some cases. The city of Woodstock in southern Ontario relies on public wells for all of its municipal supply. Several of the wells have experienced chronic increases in nitrate concentrations exceeding the maximum allowable limit of 10 mg/L N-NO3−. While BMPs are established, an interim reduction plan based on enhanced in situ denitrification (Cross Injection System, CIS) in a 15 m thick zone of high nitrate mass flux within the aquifer zone was evaluated. Based in the results of preliminary acetate injection experiments, a C:N ratio of 2.35, (approximately 260 mg acetate/L), was selected to optimize the denitrification reaction. Injections were performed for six hours a day every day for a period of approximately two months. Dissolved oxygen (DO) and nitrate concentrations recorded over time indicated that reduction of both commenced within a few days of the beginning of the acetate injections and reduced levels were maintained for the remainder of the two-month injection period. Denitrification occurred throughout the profile although nitrate reduction was the highest in the lower groundwater velocity zones. An overall reduction of nitrate of 50% was achieved through the treated section of the aquifer. It is estimated that an upscaled treatment system utilizing a treatment width of only 70 m would be sufficient to reduce the nitrate concentrations to below the drinking water limit demonstrating the potential for the CIS method to functions as an interim groundwater nitrate reduction strategy.

Results of a Phase III, Multinational, Double-blind, Placebo-controlled Study in Subjects with Relapsing Forms of Multiple Sclerosis (RMS) to Assess the Efficacy, Safety, and Tolerability of GA Depot, a Long-Acting IM Injection of Glatiramer Acetate, Administered Once Every Four Weeks (P6-3.014)

Results of a Phase III, Multinational, Double-blind, Placebo-controlled Study in Subjects with Relapsing Forms of Multiple Sclerosis (RMS) to Assess the Efficacy, Safety, and Tolerability of GA Depot, a Long-Acting IM Injection of Glatiramer Acetate, Administered Once Every Four Weeks (P6-3.014)

Delayed Onset Cryptogenic Organizing Pneumonia in Alemtuzumab Treatment Patient (P14-3.004)

<h3>Objective:</h3> NA <h3>Background:</h3> Alemtuzumab is a highly effective disease modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS). However, its use carries known risk of immune-mediated conditions, including autoimmune thyroid disease, nephropathies, immune thrombocytopenia, acquired hemophilia, and rheumatoid arthritis. Numerous other autoimmune-related adverse effects are rare but have also been reported. We report a case of alemtuzumab-associated cryptogenic organizing pneumonia. <h3>Design/Methods:</h3> We present a 40-year-old female who was diagnosed RRMS at age 19, in 2001. She was initially treated with interferon beta-1a and glatiramer acetate injections, but discontinued due to drug intolerance. In 2003, she received 2 cycles of alemtuzumab as part of the Ilex/Campath-1H drug trial. <h3>Results:</h3> In 2018, she was identified to have persistent perihilar ground-glass infiltrates on CT thorax in the context of developing dyspnea on exertion, pleuritic pain and productive cough. Serologies and repeated bronchoscopies were unremarkable. She underwent lung biopsy which showed evidence of cryptogenic organizing pneumonia. She was started on prednisone which improved her pulmonary symptoms and perihilar infiltrates. Unfortunately, she did not tolerate prednisone taper and developed worsening symptoms and radiographic findings on lower dose of prednisone. Due to concern for worsening lower extremity edema and obesity, she was eventually transitioned from prednisone to mycophenolate mofetil. From a RRMS standpoint, she remained relapse-free following alemtuzumab and was not treated with additional DMT. <h3>Conclusions:</h3> We present a rare, non-infectious steroid-responsive lung disorder following alemtuzumab administration. While autoimmunity is common following alemtuzumab treatment, delayed onset cryptogenic organizing pneumonia has not been reported with its use in the literature. <b>Disclosure:</b> Dr. Cheng has nothing to disclose. Dr. Lannen has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Genentech. Dr. Lannen has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for TG Therapeutics.

A novel mushroom (Auricularia polytricha) glycoprotein protects against lead-induced hepatoxicity, promotes lead adsorption, inhibits organ accumulation of lead, upregulates detoxifying proteins, and enhances immunoregulation in rats.

Lead is a ubiquitous environmental and industrial pollutant. Its nonbiodegradable toxicity induces a plethora of human diseases. A novel bioactive glycoprotein containing 1.15% carbohydrate, with the ability of adsorbing lead and effecting detoxification, has been purified from Auricularia polytricha and designated as APL. Besides, its mechanisms related to regulation of hepatic metabolic derangements at the proteome level were analyzed in this study. Chromatographic techniques were utilized to purify APL in the current study. For investigating the protective effects of APL, Sprague-Dawley rats were given daily intraperitoneal injections of lead acetate for establishment of an animal model, and different dosages of APL were gastrically irrigated for study of protection from lead detoxification. Liver samples were prepared for proteomic analyses to explore the detoxification mechanisms. The detoxifying glycoprotein APL displayed unique molecular properties with molecular weight of 252-kDa, was isolated from fruiting bodies of the edible fungus A. polytricha. The serum concentrations of lead and the liver function biomarkers aspartate and alanine aminotransferases were significantly (p<0.05) improved after APL treatment, as well as following treatment with the positive control EDTA (300 mg/kg body weight). Likewise, results on lead residue showed that the clearance ratios of the liver and kidneys were respectively 44.5% and 18.1% at the dosage of APL 160 mg/kg, which was even better than the corresponding data for EDTA. Proteomics disclosed that 351 proteins were differentially expressed following lead exposure and the expression levels of 41 proteins enriched in pathways mainly involved in cell detoxification and immune regulation were normalized after treatment with APL-H. The results signify that APL ameliorates lead-induced hepatic injury by positive regulation of immune processing, and suggest that APL can be applied as a therapeutic intervention of lead poisoning in clinical practice. This report represents the first demonstration of the protective action of a novel mushroom protein on lead-elicited hepatic toxicity.