Moderate Doses Research Articles

Nationwide Big Data Analysis of Statin Use and Intracerebral Hemorrhage Risk in Acute Ischemic Stroke Patients in Taiwan.

Background and Objectives: Although statins are recommended for secondary prevention of acute ischemic stroke, some population-based studies and clinical evidence suggest that they might be used with an increased risk of intracranial hemorrhage. In this nested case-control study, we used Taiwan's nationwide universal health insurance database to investigate the possible association between statin therapy prescribed to acute ischemic stroke patients and their risk of subsequent intracerebral hemorrhage and all-cause mortality in Taiwan. Materials and Methods: All data were retrospectively obtained from Taiwan's National Health Insurance Research Database. Acute ischemic stroke patients were divided into a cohort receiving statin pharmacotherapy and a control cohort not receiving statin pharmacotherapy. A 1:1 matching for age, gender, and index day, and propensity score matching was conducted, producing 39,366 cases and 39,366 controls. The primary outcomes were long-term subsequent intracerebral hemorrhage and all-cause mortality. The competing risk between subsequent intracerebral hemorrhage and all-cause mortality was estimated using the Fine and Gray regression hazards model. Results: Patients receiving statin pharmacotherapy after an acute ischemic stroke had a significantly lower risk of subsequent intracerebral hemorrhage (p < 0.0001) and lower all-cause mortality rates (p < 0.0001). Low, moderate, and high dosages of statin were associated with significantly decreased risks for subsequent intracerebral hemorrhage (adjusted sHRs 0.82, 0.74, 0.53) and all-cause mortality (adjusted sHRs 0.75, 0.74, 0.74), respectively. Conclusions: Statin pharmacotherapy was found to safely and effectively reduce the risk of subsequent intracerebral hemorrhage and all-cause mortality in acute ischemic stroke patients in Taiwan.

Acute ethanol disrupts conditioned inhibition in the male rat.

Alcohol can disrupt conditioned sexual inhibition (CSI) established by first-order conditioning in male rats. CSI can also be induced using second-order conditioning, during which male rats are trained to associate a neutral odor with a nonreceptive female. As a result, when given access to two receptive females (one scented and one unscented) during a copulatory preference test, they display CSI toward the scented female. The present study examined the effect of low-to-moderate doses of alcohol on CSI and brain activation following exposure to alcohol and the olfactory cue alone. Sexually-naïve Long-Evans rats received alternate conditioning sessions with unscented receptive or scented (almond extract) non-receptive females. Following the conditioning phase, males were injected with saline, alcohol 0.5g/kg or 1g/kg, 45min before a copulatory test with two receptive females, with one bearing the olfactory cue. Fos activation was later assessed, following exposure to alcohol and the olfactory cue alone, in several brain regions involved in the expression and regulation of male sexual behavior. While males in the saline group displayed sexual avoidance towards the scented female, those injected with alcohol before the copulatory test, regardless of the dose, copulated indiscriminately with both females. Subsequent exposure to alcohol and the olfactory cue alone induced different Fos expression between groups in several brain regions. Low to moderate doses of alcohol disrupt conditioned sexual inhibition in male rats and induce a differential pattern of neural activation, particularly in regions involved in the expression and regulation of sexual behavior.

Low to moderate dose 137Cs (γ) radiation promotes M2 type macrophage skewing and reduces atherosclerotic plaque CD68+ cell content in ApoE(−/−) mice

The effects of low doses of ionizing radiation on atherosclerosis remain uncertain, particularly as regards the generation of pro- or anti-inflammatory responses, and the time scale at which such effects can occur following irradiation. To explore these phenomena, we exposed atheroprone ApoE(−/−) mice to a single dose of 0, 0.05, 0.5 or 1 Gy of 137Cs (γ) administered at a 10.35 mGy min−1 dose rate and evaluated short-term (1–10 days) and long-term consequences (100 days). Bone marrow-derived macrophages were derived from mice 1 day after exposure. Irradiation was associated with a significant skewing of M0 and M2 polarized macrophages towards the M2 phenotype, as demonstrated by an increased mRNA expression of Retnla, Arg1, and Chil3 in cells from mice exposed to 0.5 or 1 Gy compared with non-irradiated animals. Minimal effects were noted in M1 cells or M1 marker mRNA. Concurrently, we observed a reduced secretion of IL-1β but enhanced IL-10 release from M0 and M2 macrophages. Effects of irradiation on circulating monocytes were most marked at day 10 post-exposure, when the 1 Gy dose was associated with enhanced numbers of both Ly6CHigh and Ly6Low cells. By day 100, levels of circulating monocytes in irradiated and non-irradiated mice were equivalent, but anti-inflammatory Ly6CLow monocytes were significantly increased in the spleen of mice exposed to 0.05 or 1 Gy. Long term exposures did not affect atherosclerotic plaque size or lipid content, as determined by Oil red O staining, whatever the dose applied. Similarly, irradiation did not affect atherosclerotic plaque collagen or smooth muscle cell content. However, we found that lesion CD68+ cell content tended to decrease with rising doses of radioactivity exposure, culminating in a significant reduction of plaque macrophage content at 1 Gy. Taken together, our results show that short- and long-term exposures to low to moderate doses of ionizing radiation drive an anti-inflammatory response, skewing bone marrow-derived macrophages towards an IL-10-secreting M2 phenotype and decreasing plaque macrophage content. These results suggest a low-grade athero-protective effect of low and moderate doses of ionizing radiation.

Psychotropic medications and mortality from cardiovascular disease and suicide for individuals with depression in Taiwan

BackgroundPolypharmacy for treatment of depression has been increasing in Taiwan. MethodsIndividuals having depressive disorders were identified in a national database for healthcare services and followed up for 5 years. The mean dosage of antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotics was calculated; the associations between the exposure dosage to different psychotropic medications and patients’ overall death and death due to cardiovascular diseases (CVD) and suicide were examined. ResultsA total of 400,042 individuals with depressive disorders (63.8% women) were identified. Compared with those with no exposure to antidepressants, patients prescribed antidepressants had decreased mortality. Use of antipsychotics had a dose-related increase in overall mortality risk compared to no exposure group. Contrarily, depressed patients taking sedative-hypnotics had decreased overall and CVD mortality compared to no exposure group, with the most prominent decrease in CVD mortality of up to 54.9% for those in the moderate exposure group (hazard ratio: 0.451, 95% confidence interval: 0.405–0.503). A moderate or high dose of antidepressants or sedative-hypnotics was shown to be associated with a significantly increased mortality for suicide compared to those with no exposure. ConclusionsAntidepressant and sedative-hypnotic use was associated with decreased all-cause and CVD-related mortality and use of antipsychotics was associated with a dose-related increase in mortality risk. Future studies are needed to further clarify the involved mechanisms and benefits and risks should be carefully weighed when prescribing psychotropic medications in patients with depressive disorders.

Impact of SMAASH-C, a novel nutritional supplement, on drug-seeking and toxicity in female and male rats.

Relapse to drug use after abstinence is a major challenge in treating substance use disorder. Exposure to drug-associated cues during abstinence can trigger intense craving and precipitate relapse. New and more effective anti-relapse interventions are critically needed, particularly for cocaine use disorder since no effective pharmacological intervention is available. We discovered that a nutritional supplement we developed as part of a nutritional approach for managing patients with substance use disorder reduced patient reports of drug craving and relapse. The goal of this study was to determine the efficacy of this supplement, SMAASH-C, at reducing drug-craving/relapse vulnerability in males and females in rat models with cocaine. Effects were determined following extended-access cocaine self-administration (24-hr/day for 10 days) and a two-week treatment regimen at a moderate and moderate-to-high dose (0.4 and 0.8 g/kg/day) as well as a 6-week regimen at a moderate dose (0.4 g/kg/day; Experiment 2). We also determined its efficacy to offset serum markers of organ toxicity in response to chronic cocaine self-administration and abstinence (aspartate transaminase, alanine transaminase, amylase; urea nitrogen). In females, both the 2- and 6-week SMAASH-C treatment regimens reduced cocaine-seeking (extinction or cue-induced reinstatement), particularly when drug-seeking was heightened (e.g., during estrus). Despite a lack of efficacy to reduce drug-seeking in males, SMAASH-C treatment normalized cocaine/abstinence-induced increases in serum levels of aspartate transaminase and amylase, which are markers of liver and pancreatic toxicity respectively. Thus, the beneficial effects of oral SMAASH-C treatment over abstinence following chronic cocaine self-administration appears to be sex-specific.

Gamma-irradiation-induced tailoring of physical, electrical, optical, and mechanical properties of PVC/PANI/TiO2 nanocomposites for different applications

Gamma irradiation exhibits a complex influence on the properties of PVC/PANI/TiO2 nanocomposite films. XRD analysis reveals a non-monotonic response in crystallinity, with an initial increase at lower doses due to crosslinking followed by a decrease at higher doses attributed to polymer chain scission. Mechanical properties exhibit an improvement in tensile strength and Young's modulus at moderate doses (up to 100 kGy) due to crosslinking. However, excessive irradiation (>100 kGy) induces chain degradation, causing a decrease in both tensile strength and elongation at break. Similar dose-dependent behavior is observed in thermal properties, with moderate doses improving thermal stability and melting temperature before a decline at higher doses due to chain degradation. Gamma irradiation significantly affects AC conductivity, suggesting potential changes in structure, charge carrier density, and conduction mechanisms. While the core chemical structure remains largely unaffected, FTIR and UV–Vis spectroscopy analyses indicate alterations in the degree of crosslinking and optical properties, warranting further investigation. Refractive index increases with irradiation due to enhanced density and changes in polarizability. This study highlights the importance of tailoring the gamma irradiation dose to achieve desired properties in PVC/PANI/TiO2 nanocomposite films for various applications.

Effects of Hemorrhagic Shock and Rhabdomyolysis on Renal Microcirculation, Oxygenation, and Function in a Female Swine Model.

Hemorrhagic shock (HS) and rhabdomyolysis (RM) are two important risk factors for acute kidney injury after severe trauma; however, the effects of the combination of RM and HS on kidney function are unknown. The purpose of this study was to determine the impact of RM and HS on renal function, oxygenation, perfusion, and morphology in a pig model. Forty-seven female pigs were divided into five groups: sham, RM, HS, HS and moderate RM (RM4/HS), and HS and severe RM (RM8/HS). Rhabdomyolysis was induced by intramuscular injection of glycerol 50% with a moderate dose (4 ml/kg for the RM4/HS group) or a high dose (8 ml/kg for the RM and RM8/HS groups). Among animals with HS, after 90 min of hemorrhage, animals were resuscitated with fluid followed by transfusion of the withdrawn blood. Animals were followed for 48 h. Macro- and microcirculatory parameters measurements were performed. RM alone induced a decrease in creatinine clearance at 48 h (19 [0 to 41] vs. 102 [56 to 116] ml/min for RM and sham, respectively; P = 0.0006) without alteration in renal perfusion and oxygenation. Hemorrhagic shock alone impaired temporarily renal microcirculation, function, and oxygenation that were restored with fluid resuscitation. The RM4/HS and RM8/HS groups induced greater impairment of renal microcirculation and function than HS alone at the end of blood spoliation that was not improved by fluid resuscitation. Mortality was increased in the RM8/HS and RM4/HS groups in the first 48 h (73% vs. 56% vs. 9% for the RM8/HS, RM4/HS, and HS groups, respectively). The combination of HS and RM induced an early deleterious effect on renal microcirculation, function, and oxygenation with decreased response to resuscitation and transfusion compared with HS or RM alone.

Coenzyme Q10 alleviates depression-like behaviors in mice with chronic restraint stress by down-regulating the pyroptosis signaling pathway

To explore the neuroprotective effect of coenzyme Q10 and its possible mechanism in mice with chronic restraint stress (CRS). Mouse models of CRS were treated with intraperitoneal injections of coenzyme Q10 at low, moderate and high doses (50, 100 and 200 mg/kg, respectively, n=8), VX765 (a caspase-1 specific inhibitor, 50 mg/kg, n=8), or fluoxetine (10 mg/kg, n=8) on a daily basis for 4 weeks, and the changes in depression-like behaviors of the mice were assessed by sugar water preference test, forced swimming test and tail suspension test. The expression of glial fibrillary acidic protein (GFAP) in the hippocampus of the mice was detected using immunohistochemistry, and the number of synaptic spines was determined with Golgi staining. Western blotting was performed to detect the changes in the expressions of GFAP and pyroptosis-related proteins in the hippocampus, and the colocalization of neurons and caspase-1 p10 was examined with immunofluorescence assay. Compared with the normal control mice, the mouse models of CRS showed significantly reduced sugar water preference and increased immobility time in forced swimming and tail suspension tests (P < 0.05), and these depression-like behaviors were obviously improved by treatment with coenzyme Q10, VX765 or FLX. The mouse models showed a significantly decreased positive rate of GFAP and lowered GFAP protein expression in the hippocampus with obviously decreased synaptic spines, enhanced expressions of GSDMD-N, caspase-1 and IL-1β, and increased colocalization of neurons and caspase-1 p10 (all P < 0.05). All these changes were significantly ameliorated in the mouse models after treatment with Q10. Coenzyme Q10 can alleviate depression-like behaviors in mice with CRS by down-regulating the pyroptosis signaling pathway.

The Role of Pigments and Cryptochrome 1 in the Adaptation of Solanum lycopersicum Photosynthetic Apparatus to High-Intensity Blue Light.

The effects of high-intensity blue light (HIBL, 500/1000 µmol m-2s-1, 450 nm) on Solanum lycopersicum mutants with high pigment (hp) and low pigment (lp) levels and cryptochrome 1 (cry1) deficiency on photosynthesis, chlorophylls, phenols, anthocyanins, nonenzymatic antioxidant activity, carotenoid composition, and the expression of light-dependent genes were investigated. The plants, grown under white light for 42 days, were exposed to HIBL for 72 h. The hp mutant quickly adapted to 500 µmol m-2s-1 HIBL, exhibiting enhanced photosynthesis, increased anthocyanin and carotenoids (beta-carotene, zeaxanthin), and increased expression of key genes involved in pigment biosynthesis (PSY1, PAL1, CHS, ANS) and PSII proteins along with an increase in nonenzymatic antioxidant activity. At 1000 µmol m-2s-1 HIBL, the lp mutant showed the highest photosynthetic activity, enhanced expression of genes associated with PSII external proteins (psbO, psbP, psbQ), and increased in neoxanthin content. This mutant demonstrated greater resistance at the higher HIBL, demonstrating increased stomatal conductance and photosynthesis rate. The cry1 mutant exhibited the highest non-photochemical quenching (NPQ) but had the lowest pigment contents and decreased photosynthetic rate and PSII activity, highlighting the critical role of CRY1 in adaptation to HIBL. The hp and lp mutants use distinct adaptation strategies, which are significantly hindered by the cry1 mutation. The pigment content appears to be crucial for adaptation at moderate HIBL doses, while CRY1 content and stomatal activity become more critical at higher doses.

Synergy of lytic phage pB23 and meropenem combination against carbapenem-resistant Acinetobacter baumannii.

Phage-antibiotic combination treatment is a novel noteworthy drug delivery method in anti-infection. In the current study, we have isolated a new phage, pB23, against carbapenem-resistant Acinetobacter baumannii 2023. Synergistic antibacterial effect between phage pB23 and meropenem combination could be more stable, using moderate doses of phage (multiplicity of infection ranging from 0.1 to 1,000) based on results of in vitro antibacterial activity. Phage pB23 and meropenem combination could effectively clear mature biofilms and prevent biofilm formation of carbapenem-resistant Acinetobacter baumannii in vitro. Phage pB23 and meropenem combination also has good synergistic antibacterial effects against carbapenem-resistant Acinetobacter baumannii in different growth phases under static culture conditions. The pig skin explant model shows that phage pB23 and meropenem combination has a synergistic effect to remove bacteria from wounds ex vivo. Phage pB23 and meropenem combination also exhibited a synergistic antibacterial effect in vivo using a zebrafish infection mode. The potential promotion of phage proliferation by meropenem and the sensitivity recovery of phage-resistant bacteria to meropenem might elucidate the mechanism of the synergistic antimicrobial activity. In summary, our study illustrates that phage pB23 and meropenem combination could produce synergistic antibacterial effects against carbapenem-resistant Acinetobacter baumannii under static growth conditions. This study also demonstrates that phage-antibiotic combination will become an effective strategy to enhance antibacterial activity of individual drug and provide a new idea of the drug development for the treatment of infections due to carbapenem-resistant Acinetobacter baumannii and other multidrug-resistant bacteria.

Provocative Findings From a Transdiagnostic Counseling Intervention to Improve Psychiatric Comorbidity and HIV Care Engagement Among People With HIV: A Pilot Randomized Clinical Trial.

Depression, anxiety, post-traumatic stress, and alcohol/substance use disorders are prevalent among people with HIV (PWH), commonly co-occur, and predict worse HIV care outcomes. Transdiagnostic counseling approaches simultaneously address multiple co-occurring mental health disorders. We conducted a pilot individually randomized trial of the Common Elements Treatment Approach adapted for people with HIV (CETA-PWH), a transdiagnostic counseling intervention, compared with usual care at a large academic medical center in the southern United States. Participants were adults with HIV; at risk for HIV care disengagement; and with elevated symptoms of depression, anxiety, post-traumatic stress, and/or alcohol/substance use. Mental health and HIV care engagement were assessed at 4 and 9 months. Among participants (n = 60), follow-up was high at 4 (92%) and 9 (85%) months. Intervention engagement was challenging: 93% attended ≥1 session, 43% attended ≥6 sessions in 3 months ("moderate dose"), and 30% completed treatment. Although not powered for effectiveness, mental health outcomes and HIV appointment attendance improved in CETA-PWH relative to usual care in intent-to-treat analyses; those receiving a moderate dose and completers showed progressively greater improvement. Viral load showed small differences between arms. The dose-response pattern was not explained by differences between those who did and did not complete treatment. This pilot trial provides preliminary evidence for the potential of CETA-PWH to simultaneously address co-occurring mental health comorbidities and support HIV appointment attendance among PWH. Additional strategies may be an important part of ensuring that clients can engage in the full course of treatment and realize its full benefits.

Analysis of Mechanical Properties of Fiber-Reinforced Soil Cement Based on Kaolin.

Adding fibers into cement to form fiber-reinforced soil cement material can effectively enhance its physical and mechanical properties. In order to investigate the effect of fiber type and dosage on the strength of fiber-reinforced soil cement, polypropylene fibers (PPFs), polyvinyl alcohol fibers (PVAFs), and glass fibers (GFs) were blended according to the mass fraction of the mixture of cement and dry soil (0.5%, 1%, 1.5%, and 2%). Unconfined compressive strength tests, split tensile strength tests, scanning electron microscopy (SEM) tests, and mercury intrusion porosimetry (MIP) pore structure analysis tests were conducted. The results indicated that the unconfined compressive strength of the three types of fiber-reinforced soil cement peaked at a fiber dosage of 0.5%, registering 26.72 MPa, 27.49 MPa, and 27.67 MPa, respectively. The split tensile strength of all three fiber-reinforced soil cement variants reached their maximum at a 1.5% fiber dosage, recording 2.29 MPa, 2.34 MPa, and 2.27 MPa, respectively. The predominant pore sizes in all three fiber-reinforced soil cement specimens ranged from 10 nm to 100 nm. Furthermore, analysis from the perspective of energy evolution revealed that a moderate fiber dosage can minimize energy loss. This paper demonstrates that the unconfined compressive strength test, split tensile strength test, scanning electron microscopy (SEM), and mercury intrusion porosimetry (MIP) pore structure analysis offer theoretical underpinnings for the utilization of fiber-reinforced soil cement in helical pile core stiffening and broader engineering applications.

An investigation of photocatalytic and biological properties of Croton bonplandianum-mediated Ag-Cu bimetallic nanoparticles

The green synthesis of nanoparticles using plant parts and their essence is considered an archetypal tactic in material synthesis for environmental beneficence. Multitudinous metal nanoparticles with potential bioactivities have been prepared based on plant extract. This study's main objective is synthesizing Ag-Cu bimetallic nanoparticles (Ag-Cu BMNPs) using leaf extract of Croton bonplandianum L (CB). Furthermore, its photocatalytic, antibacterial, anti-fungal, and anti-tuberculosis activities are systematically investigated in detail. The surface morphology of the prepared sample is shown to be highly porous, with an average grain size of ∼ 16 nm. The FTIR spectra exhibited that the phytomolecules from CB leaf extract serve as a capping and reductantfor forming Ag-Cu BMNP. Brunauer-Emmitte-Teller (BET) comprehends the CB leaf extract to be an active, cost-effective, reusable, and high surface area catalyst. The sample exhibited improved photocatalytic activity with an efficiency of 92.31 % at the moderate catalyst dose of 30 mg against methylene blue (MB) dye. Ag-Cu BMNPs exhibited a 17 mm inhibition zone at higher concentrations against both gram (+ve) and gram (−ve) bacterial strains. Also, the synthesized Ag-Cu BMNPs produced a clear inhibition zone of 16 mm and 15 mm at lower concentrations. The anti-fungal activity against A. flavus and C. albicans at higher and lower concentrations produced a clear inhibition zone of 17 mm,15 mm, and 6 mm, 9 mm, respectively. In addition, the anti-tuberculosis activity against Mycobacteria tuberculosis exhibited good results at a 0.4 µg/mL concentration for the synthesized sample. Moreover, Ag-Cu BMNPs enhanced their biological ability and did not increase their cytotoxicity, which provides a potential for the clinical applications of Ag-Cu BMNPs. In general, the suggested method for producing Ag-Cu bimetallic nanoparticles is successful in combating microbiological diseases.

Subchronic oral toxicity assessment of Ayurvedic herbo-metallic formulation Mahalaxmi Vilas Rasa in Wistar rats

Abstract BACKGROUND: Mahalaxmi Vilas (MV) Rasa, a revered Ayurvedic herbo-metallic formulation, holds historical significance for its therapeutic potential. In light of its traditional use, a rigorous evaluation of its safety profile in Wistar rats is imperative for establishing its evidence-based safety. This study aims to contribute valuable insights to the scientific community and healthcare practitioners, facilitating informed decision-making regarding the integration of MV into contemporary medical practices. The findings hold relevance for advancing our understanding of Ayurvedic formulations in the context of safety and efficacy, fostering a bridge between traditional wisdom and modern scientific scrutiny. METHODS: In the present study, a total of 24 Wistar rats were randomly divided into four groups as one control vehicle and three dose levels of the test drug MV Rasa. The test drug was made into suspension in a vehicle (honey-to-water ratio, 2:3) and administered orally once a day for 90 consecutive days in three dose levels (51.36, 205.44, and 513.6 mg/kg). Clinical observations, body weight changes, and food and water consumption were noted during the study. Then, on the 91st day, rats were sacrificed humanely, and parameters, such as hematological, biochemical, relative organ weight, and histopathological changes, were studied. RESULTS: There was a significant decrease in water intake in high-dose group rats (513.6mg/kg) in the weeks 1, 3, and 4, as compared with control group rats, the observed effect was not treatment related. In addition, MV (51.36, 205.44, and 513.6 mg/kg) produced no significant alterations in any of the hematological and biochemical parameters, except for a significant increase in direct bilirubin in the moderate dose group (205.44 mg/kg). However, no considerable cellular changes were found in the organs analyzed. CONCLUSION: MV had no toxic effect in Wistar rats during this repeated dose oral toxicity (90 days) study, even at 10 times the therapeutic dose (513.6 mg/kg). This was evidenced by their normal behavioral, hematological, biochemical, and histopathological examinations.

Low to moderate doses of dietary resistant starch and a renin-angiotensin system inhibitor exhibit nephroprotective effects through similar mechanisms in a preclinical model of diabetes

The investigative goal of our study was to determine the molecular mechanisms of nephroprotection of a drug-diet intervention for type II diabetes in a pre-clinical model. Our working hypothesis proposed that a combination of moderate doses of dietary resistant starch and a low-dose renin-angiotensin system (RAS) inhibitor would decrease renal biomarkers associated with the progression and complications of type II diabetes through the modulation of the renal renin-angiotensin system. Four weeks old Zucker Diabetic Fatty rats ( fa/fa) ( ZDF, n=48) and Zucker lean rats (n=7) were obtained from Charles River Laboratories and acclimated for one week. ZDF rats were then randomly assigned to one of three diets: AIN-93G diet with 0% resistant starch (RS), which served as the control diet, AIN-93G diet with 5% RS, or AIN-93 with 10% resistant starch, which were adjusted at the expense of cornstarch in the diet composition, for a total of eight weeks. At six weeks old, they were randomly assigned to daily intraperitoneal (IP) injections of either captopril (at a dose of 0.5 g/kg of body weight) in saline water and ascorbic acid solution or placebo solution, which consisted of just the vehicle, until the end of the 8-weeks. Zucker lean rats were assigned to an AIN-93G diet with 0% RS and administered daily IP placebo injections at the same timeline as the ZDF counterparts. Rats were placed in metabolic cages 12 hours before euthanization by exsanguination to collect urine and feces. Samples and tissues were aliquoted and frozen, respectively, until further analyses. Enzyme-linked immunosorbent assays were used to quantify different renal biomarkers in the urine and serum samples (i.e., 25-hydroxy-vitamin D, albumin, creatinine). Protein was extracted from kidney samples for Western Blot analyses. ZDF 10% RS and captopril group (ZDF 10% cap) had a decrease of 62.5% in urinary protein creatinine ratio, 29% of urinary albumin levels, and 18% of 25-hydroxy vitamin D (25D) levels, compared to the diabetic control group (ZDF 0% RS placebo). The ZDF 10% RS cap group also exhibited a 62% increase in serum 25D levels, while the 5% RS and captopril group had an 8.7% increase in 1,25-dihydroxy-vitamin D levels compared to the diabetic control. The ZDF 10% RS cap group also presented a 5.5% increase in relative abundance of nephrin and a decrease of 5.9% and 33.3% in angiotensin II receptor I and aldosterone synthase relative abundance, respectively, compared to the diabetic control group. Our results suggest that a combination of dietary resistant starch and a RAS inhibitor help to protect kidney integrity in type II diabetic rats, evidenced by a decrease of biomarkers in the urine and expression of proteins that play a part in the RAS, and increase in serum biomarkers and expression of glomerular structural proteins. Our work was funded by a USDA-NIFA grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Exploring low-dose gamma radiation effects on monoterpene biosynthesis in Thymus vulgaris: insights into plant defense mechanisms.

Thymus vulgaris, commonly known as thyme, is a plant renowned for producing monoterpenes. This study aimed to understand the effects of low-dose gamma radiation, specifically in the range of 1-5Gy, on various traits of Thymus vulgaris, providing context on its importance in agricultural and medicinal applications. The research explored morpho-physiological, biochemical, and gene-expression responses in thyme plants under no gamma- and gamma-ray exposure conditions. The study revealed complex relationships between gamma-ray doses and plant characteristics. In particular, shoot and root lengths initially increased with low doses (1-3Gy) but decreased at higher doses (5Gy), suggesting a dose-dependent threshold effect. Similarly, shoot and root fresh weights displayed an initial increase followed by a decline with increasing doses. Biochemical parameters showed dose-dependent responses, with low to moderate doses (1-3Gy) stimulating enzyme activities and high doses (5Gy) inhibiting them. Gene expression analysis was focused on the following specific genes: thymol synthase, γ-terpinene synthase, and carvacrol synthase. Low to moderate doses increased the expression of these genes, resulting in increased production of bioactive compounds. However, higher doses had diminished effects or suppressed gene expression. Metabolite analysis demonstrated dose-dependent responses, with moderate doses enhancing secondary metabolite production, while higher doses provided limited benefits. These findings underscore the implications of using gamma radiation to enhance secondary metabolite production in plants and its potential applications in agriculture, medicine, and environmental science. The study emphasizes the potential of gamma radiation as an external stressor to influence plant responses and highlights the importance of understanding such effects in various fields.

Evaluation of the effectiveness of phenylephrine in hypotension management in anesthesia for cardiac surgery using extracorporeal circulation

Background: Phenylephrine is a vasoconstrictor often chosen to raise blood pressure during induction of anesthesia. The study aimed to evaluate the effectiveness of phenylephrine in hypotension treatment in anesthesia for cardiac surgery using extracorporeal circulation. Methods: Descriptive study and evaluation of phenylephrine response in 40 cardiac surgery patients using extracorporeal circulation. Results: During the induction phase, phenylephrine increased mean arterial blood pressure the most at time T2 (mean mean ∆BP was 26.2 ± 6.9), then the trend gradually decreased and remained within normal limits (p&lt;0.05). The mean number of intravenous injections of phenylephrine during the induction period was 1.1 ± 0.3 times, the mean dose of phenylephrine used was 0.9 ± 0.3 µg/kg. During the extracorporeal circulation phase, phenylephrine increased mean blood pressure early, and persistently, peaking at T5 (mean ∆HATB of 17.4 ± 3.6 mmHg). The mean number of intravenous injections of phenylephrine during the extracorporeal circulation phase was 1 time, the mean dose of phenylephrine used was 0.8 ± 0.3 µg/kg. Conclusion: Phenylephrine is used effectively with a small number of injections and a moderate dose when treating hypotension in anesthesia for cardiac surgery using extracorporeal circulation.

Successful treatment of concurrent cold agglutinin disease and myelodysplastic syndrome

Herein, we describe a case of severe anemia presenting with myelodysplastic syndrome with cold agglutinin disease that was successfully treated by a moderate dose of steroids followed by cyclosporine. In patients with myelodysplastic syndrome, autoimmunity in erythroid cells is occasionally demonstrated, and autoimmune hemolytic anemia is seen in some patients. However, hemolytic anemia with cold agglutinin in patients with myelodysplastic syndrome is less common, and the effect of corticosteroids for autoimmune hemolytic anemia caused by cold agglutinin is thought to be limited. Although the elevated levels of reticulocytes and LDH are usually caused by ineffective hematopoiesis in myelodysplastic syndrome, clinicians should be aware of latent cold agglutinin disease. In the present case, in addition to the improvement of erythroid dysplasia, the corticosteroid-sparing effect on cold agglutinin disease may have played a role in the mechanism underlying the effectiveness of cyclosporine.

Effect of &lt;i&gt;Polyalthia Longifolia&lt;/i&gt; Leaf Extract on Uterine Function Indices of Female Wistar Rats

The bark of Polyalthia longifolia plant is commonly used in the treatment of various diseases like diabetes, malaria and many others. In this research, phytochemical screening and effects of the aqueous extract of P. longifolia leaves on the uterine function indices of female Wistar rats were investigated. Phytochemical analysis of the extract was performed using standard methods. The animals were randomized into four groups (Control A, B, C and D) of five rats each. Animals in the control group were given 1ml of distilled water daily, for 30days. While those in groups B, C and D were administered with the same volume of 50, 100 and 200mg/kg body weight of the plant extract, respectively, for 30days as well. At the end of the administration period, the animals were sacrificed 24 hours after the last day of administration. Uterine function indices were evaluated afterwards. Phytochemical screening indicated the presence of saponins, flavonoids, tannins, phenolics, cardiac glycosides, steroids, anthraquinones, phlobatannins and alkaloids while terpenoids were not detected. The extract at a moderate dose of 100mg/kg body weight gave a significant increase and decrease (P&lt;0.05) in uterine glucose and uterine cholesterol respectively; it also revealed a significant increase and decrease(P&lt;0.05) in alkaline phosphatase activity and total protein, when compared with the control. In general, it could be inferred that the aqueous extract of P. longifolia leaves possesses fertility enhancing potentials with regards to the uterus and uterine function indices.

Registry of Members of the Association of Patients with Hereditary Angioedema of Perú

To report the registry of the HAE Peruvian patient's association. We used the questionnaire of the Latin American HAE committee. Consent was requested from the patient's association to report the data. We report data of 63 patients, 51 Female, 12 Male, range age between 6 to 74 years. Nine under 18 years old, 5/9 between 6 to 13 years. Forty-five HAE C1-INH type I, 12 HAE-FXII, 5 HAE UNK, 1 AAE. Symptoms onset average age in 56/62 HAE patients was 16.8. In a group of 50/62 adult HAE patients, the average diagnostic delay approximately was 19.3 years. Laboratory tests: we can perform C4 complement C1-inhibitor antigenic and functional tests. Treatments: The patients have access to tranexamic acid (TA) and attenuated androgens. We do not have registered specific long-term prophylaxis treatments. We used moderate/high doses of TA, in most patients up to 6 gr i.v./in 24 hours, we start with the treatment immediately the HAE acute crisis is beginning, it helps to the HAE attacks are less symptomatic, resolves in a few days and decrease the frequency. We present 63 members of the Association of Patients with Hereditary Angioedema of Perú. We have improved blood tests for HAE diagnosis. Moderate and high doses of Tranexamic Acid are used for prophylaxis and acute crisis respectively, with acceptable response. No deaths have been reported due to HAE crisis in the patient's association.