Search results for: mammalian kidney

Authors: Rukia Yosuf

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Diabetes is a national healthcare crisis related to both macrovascular and microvascular complications. We hypothesized that higher levels of physical activity are associated with lower total and visceral fat mass, lower systolic blood pressure, and increased insulin sensitivity. Participant inclusion criteria: 21-50 years old, BMI ≥ 30 kg/m2, hemoglobin A1C 5.7-6.4, fasting glucose 100-125 mg/dL, and HOMA IR ≥ 2.5. Exclusion criteria: history of diabetes, hypertension, HIV, renal disease, hearing loss, alcoholic intake over four drinks daily, use of organic nitrates or PDE5 inhibitors, and decreased cardiac function. Total physical activity was measured using accelerometers, body composition using DXA, and insulin resistance via fsIVGTT. Clinical and biochemical cardiometabolic risk factors, blood pressure and heart rate were obtained using a calibrated sphygmomanometer. Anthropometric measures, fasting glucose, insulin, lipid profile, C-reactive protein, and BMP were analyzed using standard procedures. Within our study, we found correlations between levels of physical activity in a heterogeneous group of prediabetic adults. Patients with more physical activity had a higher degree of insulin sensitivity, lower blood pressure, total visceral adipose tissue, and overall lower total mass. Total physical activity levels showed small, but significant correlations with systolic blood pressure, visceral fat, lean mass and insulin sensitivity. After normalizing for the race, age, and gender using multiple regression, these associations were no longer significant considering our small sample size. More research into prediabetes will decrease the population of diabetics overall. In the future, we could increase sample size and conduct cross sectional and longitudinal studies in various populations with prediabetes.

Keywords: diabetes, kidney disease, nephrology, prediabetes

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Authors: Syed Hadi Hasan, Devendra Kumar Singh, Viyaj Kumar

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Cr (VI) is a known toxic heavy metal and has been considered as a priority pollutant in water. The effluent of various industries including electroplating, anodizing baths, leather tanning, steel industries and chromium based catalyst are the major source of Cr (VI) contamination in the aquatic environment. Cr (VI) show high mobility in the environment and can easily penetrate cell membrane of the living tissues to exert noxious effects. The Cr (VI) contamination in drinking water causes various hazardous health effects to the human health such as cancer, skin and stomach irritation or ulceration, dermatitis, damage to liver, kidney circulation and nerve tissue damage. Herein, an attempt has been done to develop an efficient adsorbent for the removal of Cr (VI) from water. For this purpose nanosorbent composed of polyvinyl alcohol functionalized graphene oxide (GO/PVA) was prepared. Thus, obtained GO/PVA was characterized through FTIR, XRD, SEM, and Raman Spectroscopy. As prepared nanosorbent of GO/PVA was utilized for the removal Cr (VI) in batch mode experiment. The process variables such as contact time, initial Cr (VI) concentration, pH, and temperature were optimized. The maximum 99.8 % removal of Cr (VI) was achieved at initial Cr (VI) concentration 60 mg/L, pH 2, temperature 35 °C and equilibrium was achieved within 50 min. The two widely used isotherm models viz. Langmuir and Freundlich were analyzed using linear correlation coefficient (R2) and it was found that Langmuir model gives best fit with high value of R2 for the data of present adsorption system which indicate the monolayer adsorption of Cr (VI) on the GO/PVA. Kinetic studies were also conducted using pseudo-first order and pseudo-second order models and it was observed that chemosorptive pseudo-second order model described the kinetics of current adsorption system in better way with high value of correlation coefficient. Thermodynamic studies were also conducted and results showed that the adsorption was spontaneous and endothermic in nature.

Keywords: adsorption, GO/PVA, isotherm, kinetics, nanosorbent, thermodynamics

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Authors: Abdolrasoul Daneshjoo

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The purpose of this research was to study the effect of aerobic exercises with 75% heart beats on the amount of urea, uric acid and creatine in blood of Iranian soccer national U-23 players. 27 players were selected according to the following demographic specifications: age: 21.4±1.60 years old; weight: 68±9.4 kg; height: 174.2±8.6 cm. Urea, uric acid and creatine in blood are considered as dependent variations where as 40 minutes running on a track with maximum 75% heart beats are independent variations. Heart beat and blood pressure in rest time, age, height, and weight are considered as the controlled variations. Maximum heart beats are recorded under maximum exercises (8 minutes and 150-250 watt energy) on ergo meter. Then, in order to determine independent variations, 75% maximum heart beats are considered for each player. Blood is taken twice (before and after determining independence variation). Moreover, the players are given a few instructions to be fulfilled 24 hours before the main exercises. Laboratory analysis method for blood urea sample is deacetyl ammoniom, for uric acid Karvy test and for creatine pyric acid. 'T' formula is applied for analyzing statistical data in dependent groups with degree of freedom 7 (d.f=7) urea and uric acid contain P>0.01 and P>0.05 for creatine. 1. Aerobic exercise can effect on the concentration of urea of blood as well as uric acid and creatine in blood serum and increase the amount of them. 2. Urea of blood serum increases from 26.75±2.59 to 28.9±2.67 (25%) with 40 minutes running and 75% heart beat. 3. Aerobic exercise causes uric acid increase 12.5% from 5.7±0.52 (before exercise) to 6.1±0.71 (after exercise). Creatine of blood serum increases from 1.36±0.27 (before exercise) to 1.85±0.49 (after exercise). We came to this result that during aerobic exercise catabolism of protein substrate increases. Moreover, augmentation of urea, uric acid and creatine in blood serum as metabolic poisons causes disorder in kidney. Also, tendons and joints are affected by these poisons. Appropriate diet and exercise can prevent production of these poisons resulted from heavy exercise.

Keywords: aerobic exercise, urea, uric acid, creatine, blood, soccer national players

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Authors: Vikneswaran Murugaiyah, Sultan Ayesh Mohammed Saghir, Kisantini Murugesu, Mohd. Zaini Asmawi, Amirin Sadikun

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Gynura procumbens is a popular medicinal plant used as a folk medicine in Southeast Asia to treat kidney diseases, diabetes mellitus and hyperlipidemia. The present study aims to investigate the antihyperlipidemic potential of phenolic acids rich fraction (PARF) from G. procumbens in chemically-induced acute and high fat diet-induced chronic hyperlipidemic rats. Ethanolic extract of G. procumbens leaves exhibited significant reductions in total cholesterol (TC) and triglycerides (TG) levels (P < 0.01 and P < 0.001, respectively) of poloxamer 407-induced rats compared to hyperlipidemic control after 58 h of treatment. Upon bioactivity guided fractionation the antihyperlipidemic activity was found to be concentrated in the PARF, which significantly reduced the TC and TG levels (P < 0.001). HPLC analysis revealed that 3,5-dicaffeoylquinic acid; 4,5-dicaffeoylquinic acid and chlorogenic acid are the major compounds in the PARF. Likewise, chlorogenic acid (60 mg/kg) exhibited significant reductions in TC and TG levels of hyperlipidemic rats (P < 0.001). Both chlorogenic acid and PARF significantly reduced LDL, VLDL and atherogenic index (P<0.01), while PARF increased the HDL (P < 0.01) compared to hyperlipidemic control. Both were found to be not cytotoxic against normal and cancer cell lines. In addition, LD50 of orally administered PARF was more than 5,000 mg/kg. Further investigation in high fat diet-induced chronic hyperlipidemic rats revealed that chronic administration of PARF dose-dependently restored the increase in lipids parameters. In summary, the phenolic acids rich fraction of G. procumbens leaves showed promising antihyperlipidemic effect in both chemically- and diet-induced hyperlipidemic rats that warrants further elucidation on its mechanisms of action.

Keywords: Antihyperlipidemic, Gynura procumbens, phenolic acids, chlorogenic acid, poloxamer-407, high fat diet

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Authors: Sanchir Erdenebayar, Namuuntsetseg Oyunbaatar

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Objectives: Peritoneal dialysis treatment is one of the important forms of kidney replacement therapy, and it has recently developed instantly in Mongolia for the past five years. Currently, more than 120 patients undergo peritoneal dialysis nationwide. These patients lack nutritional education, which predisposes them to protein deficiency and further impairs their quality of life. However, there is no study which is conducted among those about their dietary in Mongolia. Therefore, integrated nutrition information and educating them about dietary patterns to follow are urgently needed for PD patients. Methods: A cross-sectional study was carried out on 45 patients aged between 18 and 60 years who were undergoing CAPD at the biggest Medvic dialysis center in Ulaanbaatar. The knowledge of nutrition and food intake is assessed by interview based on a validated questionnaire prepared from KDIGO guidelines, semi-FFQ and a 24-hour dietary recall method. In addition, a biochemical blood test that includes total protein, albumin, calcium, phosphorus, potassium, and hemoglobin is used for an assessment of the patient’s current nutritional status. Results: Knowledge of nutritional status for CAPD was great, with 21.4% of patients and 78.65% having poor nutrition knowledge. The rate of mild to moderate malnutrition was 48.8% among research participants. Serum albumin was 38.4 ± 4.7 g/L, and total protein was 67.3±7.5g/l. Patients met 62.5± 26.5% of their daily intake nutritional requirement for calories and 72±40% of their nutritional requirement for protein. All patients’ energy intake was significantly /1328±304kcal/ lower than the energy requirement (2124±378kcal). Only 14.2% met the recommended dietary protein intake recommended to them of greater than 1.2 g/kg. Conclusions: As was established before, nutritional education has a vital positive impact on the health and nutritional status of peritoneal dialysis patients. The results of this study show that nutritional education programs are not enough adequate in peritoneal dialysis patients. There is a crucial priority to establish nutritional educational programs and guidelines for PD patients in Mongolia.

Keywords: renal diet, peritoneal dialysis, nutrition education, CKD diet

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Authors: Sonal Gupta, Rakhi Bansal, Javed Ali, Reema Gabrani, Shweta Dang

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Nanoemulsions (NEs) and microemulsions (MEs) have been an attractive tool for encapsulation of both hydrophilic and lipophillic actives. Both these systems are composed of oil phase, surfactant, co-surfactant and aqueous phase. Depending upon the application and intended use, both oil-in-water and water-in-oil emulsions can be designed. NEs are fabricated using high energy methods employing less percentage of surfactant as compared to MEs which are self assembled drug delivery systems. Owing to the nanometric size of the droplets these systems have been widely used to enhance solubility and bioavailability of natural as well as synthetic molecules. The aim of the present study is to assess the effect of % age of surfactants on cell viability of Vero cells (African Green Monkeys’ Kidney epithelial cells) via MTT assay. Green tea catechin (Polyphenon 60) loaded ME employing low energy vortexing and NE employing high energy ultrasonication were prepared using same excipients (labrasol as oil, cremophor EL as surfactant and glycerol as co-surfactant) however, the % age of oil and surfactant needed to prepare the ME was higher as compared to NE. These formulations along with their excipients (oilME=13.3%, SmixME=26.67%; oilNE=10%, SmixNE=13.52%) were added to Vero cells for 24 hrs. The tetrazolium dye, 3-(4,5-dimethylthia/ol-2-yl)-2,5-diphi-iiyltclrazolium bromide (MTT), is reduced by live cells and this reaction is used as the end point to evaluate the cytoxicity level of a test formulation. Results of MTT assay indicated that oil at different percentages exhibited almost equal cell viability (oilME ≅ oilNE) while surfactant mixture had a significant difference in the cell viability values (SmixME < SmixNE). Polyphenon 60 loaded ME and its PlaceboME showed higher toxicity as compared to Polyphenon 60 loaded NE and its PlaceboNE that can be attributed to the higher concentration of surfactants present in MEs. Another probable reason for high % cell viability of Polyphenon 60 loaded NE might be due to the effective release of Polyphenon 60 from NE formulation that helps in the sustenance of Vero cells.

Keywords: cell viability, microemulsion, MTT, nanoemulsion, surfactants, ultrasonication

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Authors: Magdalena Barbara Kaziuk, Waldemar Kosiba

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Introduction: Despite the development of technologies and improvements in the interior of dialysis stations, dialysis remains an unpleasant procedure, difficult to accept by the patients (who undergo it 2 to 3 times a week, a single treatment lasting several hours). Haemodialysis is one of the renal replacement therapies, in Poland most commonly used in patients with chronic or acute kidney failure. Purpose: An attempt was made to evaluate the quality of life in haemodialysed patients using the WHOQOL-BREF questionnaire. Material and methods: The study covered 422 patients (200 women and 222 men, aged 60.5 ± 12.9 years) undergoing dialysis at three selected stations in Poland. The patients were divided into 2 groups, depending on the duration of their dialysis treatment. The evaluation was conducted with the WHOQOL-BREF questionnaire containing 26 questions analysing 4 areas of life, as well as the perception of the quality of life and health self-assessment. A 5-point scale is used to answer them. The maximum score in each area is 20 points. The results in individual areas have a positive direction. Results: In patients undergoing dialysis for more than 3 years, a reduction in the quality of life was found in the physical area and in their environment versus a group of patients undergoing dialysis for less than 3 years, where a reduced quality of life was found in the areas of social relations and mental well-being (p < 0.05). A significant correlation (p < 0.01) between the two groups was found in self-perceived general health, while no significant differences were observed in the general perception of the quality of life (p > 0.05). Conclusions: The study confirmed that in patients undergoing dialysis for more than three years, the quality of life is especially reduced in their environment (access to and quality of healthcare, financial resources, and mental and physical safety). The assessment of the quality of life should form a part of the therapeutic process, in which the role of the patient in chronic renal care should be emphasised, reflected in the quality of services provided by dialysis stations.

Keywords: haemodialysis, perception of quality of life, quality of services provided, dialysis station

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Authors: Kinjal H. Shah, Piyush M. Patel

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Diabetes mellitus is considered to be a serious endocrine syndrome. Synthetic hypoglycemic agents can produce serious side effects including hematological effects, coma, and disturbances of the liver and kidney. In addition, they are not suitable for use during pregnancy. In recent years, there have been relatively few reports of short-term side effects or toxicity due to sulphonylureas. Published figures and frequency of side effects in large series of patient range from about 1 to 5%, with symptoms severe enough to lead to the withdrawal of the drug in less than 1 to 2%. Adverse effects, in general, have been of the following type: allergic skin reactions, gastrointestinal disturbances, blood dyscrasias, hepatic dysfunction, and hypoglycemia. The associated disadvantages with insulin and oral hypoglycemic agents have led to stimulation in the research for locating natural resources showing antidiabetic activity and to explore the possibilities of using traditional medicines with proper chemical and pharmacological profiles. Literature survey reveals that the inhabitants of Abbottabad district of Pakistan use the dried leaf powder along with table salt and water orally for treating diabetes, skin allergy, wounds and as a blood purifier, where they pronounced the plant locally as ‘Nem.' The detailed phytochemical investigation of the Cedrela toona Roxb. leaves for antidiabetic activity has not been documented. Hence, there is a need for phytochemical investigation of the leaves for antidiabetic activity. The collection of fresh leaves and authentification followed by successive extraction, phytochemical screening, and testing of antidiabetic activity. The blood glucose level was reduced maximum in ethanol extract at 5th and 7th h after treatment. Blood glucose was depressed by 8.2% and 10.06% in alloxan – induced diabetic rats after treatment which was comparable to the standard drug, Glibenclamide. This may be due to the activation of the existing pancreatic cells in diabetic rats by the ethanolic extract.

Keywords: antidiabetic, Cedrela toona Roxb., phytochemical screening, blood glucose

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Authors: Moetazza M. Alshafei, Ahmed M. Mabrouk, Emtenan M. Hanafi, Manal M. Ramadan, Reda M. S. Korany, Seham S. Kassem, Dina Mostafa Mohammed

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Metabolic syndrome (MeS) is a major health problem with a high incidence of obese individuals worldwide. Increased related morbidity of diabetes, hypertension and fatty liver disease, and complicated cardiovascular disease are inevitable. Boswellia serrata gum (Bos) is a promising traditional medicinal plant; it has several pharmacological properties, including anti-inflammatory, antioxidant, and antilipase activities. Probiotics (Bac) supplements have good benefits on health and MeS, whether it is supplemented in combination with prebiotics or alone. Microencapsulation helps to mask unpalatable taste and odor and deliver active ingredients to targeted organs. Methodology MeS rat model was produced by feeding rats with a high fat, high CHO diet (HFD). Bos was extracted, and both Bos and the probiotic were microencapsulated with a spray drier. Female rats were divided into 5 groups (N8). HFD control, control normal receiving basic diet, HFD treated, from the start of the experiment, either with encapsulated Bos, Bac and Bos or Bac only, all treatments were received for eight weeks (after approval from NRC animal ethical committee). Serum was collected to analyze lipid profile, blood sugar, liver and kidney functions, antioxidants, leptin, and progesterone. Rat's organs and body fat were weighed and collected for histopathology. Statistical analysis was done by use of one way Anova test in the SPSS program. Results showed control of elevated body weight, lipid profile, and glucose levels as well as decrease of body fat index and improvement of histopathology of liver and heart, especially in combination. Conclusion: We concluded that both microencapsulated Bos and probiotics have a controlling effect on MeS parameters.

Keywords: metabolic syndrome, Boswellia serata, probiotic, micro-encapsulation, histopathology, liver steatosis

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Authors: Sameer A. Pathan, Biswadev Mitra, Zain A. Bhutta, Isma Qureshi, Elle Spencer, Asmaa A. Hameed, Sana Nadeem, Ramsha Tahir, Shahzad Anjum, Peter A. Cameron

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Background: This study aimed to compare epidemiology, clinical presentations, management and outcomes of renal colic presentations in two major academic centers and discuss potential implications of these results for the applicability of current evidence in the management of renal colic. Methods: We undertook a retrospective cohort study of patients with renal colic who presented to the Hamad General Hospital Emergency Department (HGH-ED), Qatar, and The Alfred ED, Melbourne, Australia, during a period of one year from August 1, 2012, to July 3, 2013. Cases were identified using ICD-9-CM codes, and an electronic template was used to record the data on predefined clinical variables. Results: A total of 12,223 from the HGH-ED and 384 from The Alfred ED were identified as renal colic presentations during the study period. The rate of renal colic presentations at the HGH-ED was 27.9 per 1000 ED visits compared to 6.7 per 1000 ED visits at The Alfred ED. Patients presenting to the HGH-ED were significantly younger [34.9 years (29.0- 43.4) than The Alfred ED [48 years (37-60); P < 0.001]. The median stone size was larger in the HGH-ED group [6 (4-8) mm] versus The Alfred ED group [4 (3-6) mm, P < 0.001]. The intervention rate in the stone-positive population was significantly higher in the HGH-ED group as opposed to The Alfred ED group (38.7% versus 11.9%, p<0.001). At the time of discharge, The Alfred ED group received less analgesic prescriptions (55.8% versus 83.5%, P < 0.001) and more tamsulosin prescriptions (25.3% versus 11.7%, P < 0.001). Conclusions: Renal colic presentations to the HGH-ED, Qatar, were younger, with larger stone size, compared to The Alfred ED, whereas, medical expulsion therapy use was higher at the Alfred ED. Differences in epidemiology should be considered while tailoring strategies for effective management of patients with renal colic in the given setting.

Keywords: kidney stones, urolithiasis, nephrolithiasis, renal colic, epidemiology

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Authors: O’Day Luke

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Purpose: To validate virtual non-contrast reconstructions generated from dual-layer spectral computed tomography (DL-CT) data as an alternative for the acquisition of a dedicated true non-contrast dataset during multiphase contrast studies. Material and methods: Thirty-three patients underwent a routine multiphase clinical CT examination, using Dual-Layer Spectral CT, from March to August 2021. True non-contrast (TNC) and virtual non-contrast (VNC) datasets, generated from both portal venous and arterial phase imaging were evaluated. For every patient in both true and virtual non-contrast datasets, a region-of-interest (ROI) was defined in aorta, liver, fluid (i.e. gallbladder, urinary bladder), kidney, muscle, fat and spongious bone, resulting in 693 ROIs. Differences in attenuation for VNC and TNV images were compared, both separately and combined. Consistency between VNC reconstructions obtained from the arterial and portal venous phase was evaluated. Results: Comparison of CT density (HU) on the VNC and TNC images showed a high correlation. The mean difference between TNC and VNC images (excluding bone results) was 5.5 ± 9.1 HU and > 90% of all comparisons showed a difference of less than 15 HU. For all tissues but spongious bone, the mean absolute difference between TNC and VNC images was below 10 HU. VNC images derived from the arterial and the portal venous phase showed a good correlation in most tissue types. The aortic attenuation was somewhat dependent however on which dataset was used for reconstruction. Bone evaluation with VNC datasets continues to be a problem, as spectral CT algorithms are currently poor in differentiating bone and iodine. Conclusion: Given the increasing availability of DL-CT and proven accuracy of virtual non-contrast processing, VNC is a promising tool for generating additional data during routine contrast-enhanced studies. This study shows the utility of virtual non-contrast scans as an alternative for true non-contrast studies during multiphase CT, with potential for dose reduction, without loss of diagnostic information.

Keywords: dual-layer spectral computed tomography, virtual non-contrast, true non-contrast, clinical comparison

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Authors: Donna Erika E. De Jesus

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Introduction: Cardiac arrest occurs when abrupt cessation of cardiac function results in loss of effective circulation and complete cardiovascular collapse. For every minute of cardiac arrest without early intervention (cardiopulmonary resuscitation [CPR], defibrillation), chances of survival drop by 7-10%. It is crucial that CPR be initiated within 4-6 minutes to avoid brain death. Most out-of-hospital cardiac arrests (OHCA) occur in a residential setting where access to trained personnel and equipment is not readily available, resulting in poor victim outcomes. Methods: This is a descriptive study done from August to November 2021 using a prospective cohort design. Participants of the study include adult patients aged 18 years and above brought to the emergency room who suffered from out-of-hospital cardiac arrest. Out of the total 102 cases of OHCA, 63 participants were included in the study. Descriptive statistics were used to summarize the demographic and clinical characteristics of the patients. Results: 43 were male patients, comprising the majority at 73.02%. Hypertension was identified as the top co-morbidity, followed by diabetes mellitus, heart failure, and chronic kidney disease (CKD). Medical causes of arrest were identified in 96.83% of the cases. 90.48% of cardiac arrests occurred at home. Only 26 patients (41.27%) received pre-hospital intervention prior to ER arrival, which comprised only hands-only CPR. Twenty-three of which were performed by individuals with background knowledge of CPR. 60.32% were brought via self-conduction, the remainder by ambulances, which were noted to have no available equipment necessary to provide proper resuscitation. The average travel time from dispatch to ER arrival is 20 minutes. Conclusion: Overall survival of OHCA in our local setting remains dismal, as a return of spontaneous circulation was not achieved in any of the patients. The small number of patients having pre-hospital CPR indicates the need for emphasis on training and community education.

Keywords: out-of-hospital cardiac arrest, cardiopulmonary resuscitation, basic life support, emergency medical services

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Authors: Jose Carlos Tavares Carvalho, Hady Keita, Giovanna Rocha Santana, Igor Victor Ferreira Dos Santos, Jesus Rafael Rodriguez Amado, Ariadna Lafourcade Prada, Adriana Maciel Ferreira, Helison Oliveira

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Summary: As animal model, zebrafish can be a good opportunity to establish a profile of tissue alteration caused by Bothrops alternatus venom and to screen new anti-venom drugs. Objective: To establish tissue biomarkers from zebrafish injected by snake venom and elucidate the use of glucocorticoids in ophidic accidents. Materials and Methods: The Danio rerio fish were randomly divided into four groups: control group, venom group, Dexamethasone1h before venom injected group and Dexamethasone 1 h after venom injected group. The concentration of Bothrops alternatus venom was 0.13 mg/ml and the fish received 20µl/Fish. The Body weight measurement and histological characteristics of gills, kidneys, liver, and intestine were determinate. Results: Physical analysis shows necrosis accompanied by inflammation in animals receiving the Bothrops alternatus venom. Significant difference was observed in the variation of weight between the control group, and the groups received the venom (t student test, p < 0.05). The average histological alterations index of gill, liver, kidney or intestine was statistically higher in animals received the venom (t Student test, p < 0.05). The alterations were lower in the groups that received Dexamethasone 1h before and after venom injected compared to the group that received only the venom. Dexamethasone 1h before venom injected group had minor histopathological alterations. Conclusion: The organs of zebrafish may be a tissue biomarker of alterations from Bothrops alternatus venom and dexamethasone reduced the damage caused by this venom in the organs studied, which may suggest the use of zebrafish as animal model for research related to screening new drug against snake venom.

Keywords: zebrafish, snake venom, biomarker, drugs

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Authors: C. Mayuren, C. K. Paul Wang, K. Purushotham, C. Dinesh Kumar

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Diabetes Mellitus (DM) is one of the most common non-communicable diseases globally. Although significant advances have led to better understanding of the condition and the development of effective therapies and preventive strategies, the pathway to cure remains elusive and DM prevails as a serious medical challenge in the 21st century. Oxidative stress has been suggested to contribute to the progression and pathophysiological conditions of diabetes. Madecassoside (MA) a major pentacyclic triterpenoid, has been demonstrated to possess various biological activities. However, no attempt has been made to study the antioxidant activity in diabetic rats. Therefore, the present study is aimed to evaluate the antioxidant effect of MA on streptozotocin-nicotinamide induced type-2 diabetes in Sprague-Dawley rats. The study protocol was approved by the institutional ethical committee prior to the conduct of research. Adult male Sprague-Dawley rats weighing 250-300 g were used in the study. The animals were rendered diabetic with a single intraperitoneal dose of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). The diabetic animals after a stabilisation period of 14 days received various treatments (Madecassoside 50 mg/kg; Glimepiride 2.5 mg/kg) suspended in 0.5% carboxymethyl cellulose orally, for a period of 28 days. The animals fasted overnight after the last treatment were sacrificed and the pancreas, liver and kidneys were isolated. The weighted quantity of the samples of various treatments were homogenised in ice-cold condition and were subjected to lipid peroxidation, catalase and superoxide dismutase assay. The data’s obtained were subjected to statistical analysis. Diabetic rats showed significant increase in lipid peroxidation and decrease in enzymatic antioxidant levels. All the treated groups had significantly higher SOD, CAT and reduced LPO activity in the pancreas, liver and kidney. Results suggest madecassoside to have potential antioxidant effect against the diabetic model. However further investigations are necessary to study the mechanism at the cellular level.

Keywords: antioxidant, diabetes, madecassoside, nicotinamide, streptozotocin

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Authors: Prerna Kalra, Surender Singh

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Cisplatin is the most common chemotherapeutic agent used in different solid tumors, but its main limiting factor is dose-dependent nephrotoxicity by generating reactive oxygen species, by stimulating inflammatory and apoptotic pathways. Additional adjuvant therapies to decrease the toxicity of this chemotherapeutic drug are essential. This study was designed to evaluate the protective role of Emblica officinalis Geartn (Indian gooseberry) against cisplatin induced nephrotoxicity. Emblica officinalis was orally administered to Wistar rats (n=6) for 10 days in 50, 100 and 200mg/kg body weight. On day 7, 8mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. Serum creatinine, blood urea nitrogen and antioxidant levels were measured on day10. The renal damage was evaluated by histopathological and transmission electron microscopy. We found that 200mg/kg dose of Emblica officinalis significantly inhibited the elevation of biochemical parameters i.e. serum creatinine, blood urea nitrogen, oxidant stress marker (malondialdehyde) and increased the reduced levels of antioxidant marker (endogenous glutathione and superoxide dismutase). Cisplatin treated rats have shown acute tubular necrosis and infiltration of inflammatory cells in rat kidney which was reversed after treating the animals with Emblica officinalis in the treatment group. In ultrastructural changes cisplatin treated group showed the damaged mitochondria (M) with dissolved cristae and large number of lysosomes (L) and vacuole (V) formation in tubular epithelial cells. EOE administered group showed visible cristae formation and sign of autophagy vacuoles at a dose of 200mg/kg. Further in-silico studies revealed that ellagic acid is responsible for its nephroprotective effect. The above findings conclude that the Emblica officinalis may be used as an adjuvant therapy in cisplatin induced nephrotoxicity.

Keywords: antioxidant, cisplatin, Emblica officinalis, in silico, nephrotoxicity

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Authors: Alexandru Grigorescu, Alexandra Protesanu

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Background: Approximately 34-67 percent of cancer patients experience an episode of uncontrolled pain during the course of their disease, depending on the stage. The aim is to provide evidence-based data for pain prevalence, diagnosis and treatment recommendations on an integrative model of medical oncology and palliative care for patients with cancer diagnostic in a day hospital. Patients and method: Consultation registers and electronic records of 166 Patients (Pts) were studied from April 2022 to March 2023. Pts with pain syndrome were selected. The pain was objectified by the visual pain scale. To elucidate the causes of the pain, investigations were carried out: bone scintigraphy, CT scan, and PET-CT. The analgesic treatments were represented by weak and strong morphine, radiotherapy, and bisphosphonates. Result: During the mentioned period, 166 oncological patients (74 women and 92 men) were treated in the oncology day hospitalization service. There were 1,500 consultations, 40 of which were only for pain. The neoplastic locations were: gynecological, malignant melanoma, breast, gastric, bronchopulmonary, colorectal, liver, pancreatic, bladder, and kidney. 70 Pts presented pain syndrome. The causes of the pain were represented by bone metastases, compressive tumors, and post-surgical status. Drug treatment: Tramadol 47 Pts, of which 10 switched to a major opioid (Oxycodonum, Morphine sulfate), 20 Pts were treated with Oxycodonum as the first intention. In 5 patients ry to rotated morphine, 20 Pts received palliative radiotherapy, 10 Pts were treated with bisphosphonates. 2 Pts required neurosurgery consultation for an antalgic intervention. 5 Pts had important adverse reactions to morphine. All patients and their families were advised by a medical oncologist and psychologist for a lifestyle change. Conclusions: The prevalence of pain was similar to that described in the literature. In most cases, the pain could be managed in the day hospital. Weak and strong morphine represented the main pain therapy. Palliative radiotherapy was the second most effective therapy. Treatment with bisphosphonates was useful. Surgical interventions were rarely indicated. Discussions with patients and their families regarding the lifestyle change were important.

Keywords: cancer pain, opioids, medical oncology, palliative care

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Authors: Rajesh Kumar Suman, Ipseeta Ray Mohanty, Manjusha K. Borde, Ujjawala maheswari, Y. A. Deshmukh

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Background: Metabolic syndrome encompasses cluster of risk factors for cardiovascular disease which includes abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. The incidence of metabolic syndrome is on the rise globally. Objective: The present study was designed to develop a unique animal model that will mimic the pathological features seen in a large pool of individuals with diabetes and metabolic syndrome; suitable for pharmacological screening of drugs beneficial in this condition. Material and Methods: A combination of high fat diet (HFD) and low dose of streptozotocin (STZ) at 30, 35 and 40 mg/kg was used to induce metabolic syndrome co-existing with diabetes mellitus in Wistar rats. Results: The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for our study to induce diabetes mellitus. Rat fed HFD (HF-DC) group showed significant (p < 0.001) increase in body weight on 4th and 7th week as compared with NC (Normal Control) group rats. However, the increase in body weight of HF-DC group rats was not sustained at the end of 10th weeks. Various components of metabolic syndrome such as dyslipidemia {(Increased Triglyceride, total Cholesterol, LDL Cholesterol and decreased HDL Cholesterol)}, diabetes mellitus (Blood Glucose, HbA1c, Serum Insulin, C-peptide), hypertension {Systolic Blood pressure (p < 0.001)} were mimicked in the developed model of metabolic syndrome co existing with diabetes mellitus. In addition significant cardiac injury as indicated by CPK-MB levels, artherogenic index, hs-CRP. The decline in hepatic function {(p < 0.01) increase in the level of SGPT (U/L)} and renal function {(increase in creatinine levels (p < 0.01)} when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis and inflammation in Heart, Pancreas, Liver and Kidney of HFD-DC group as compared to NC. Conclusion: The present study has developed a unique rodent model of metabolic syndrome; with diabetes as an essential component.

Keywords: diabetes, metabolic syndrome, high fat diet, streptozotocin, rats

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Authors: Hanaa M. M. El-Khayat, Hoda Abdel-Hamid, Kadria M. A. Mahmoud, Hanan S. Gaber, Hoda, M. A. Abu Taleb, Hassan E. Flefel

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Snails are considered as suitable diagnostic organisms for heavy metal–contaminated sites. Biomphalaria alexandrina snails are used in this work as pollution bioindicators after exposure to chemical mixtures consisted of heavy metals (HM); zinc (Zn), copper (Cu) and lead (Pb); and persistent organic pollutants; Decabromodiphenyl ether 98% (D) and Aroclor 1254 (A). The impacts of these tested chemicals, individual and mixtures, on liver and kidney functions, antioxidant enzymes, complete blood picture, and tissue histology were studied. Results showed that Cu was proved to be the highly toxic against snails than Zn and Pb where LC₅₀ values were 1.362, 213.198 and 277.396 ppm, respectively. Also, B. alexandrina snails exposed to the mixture of HM (¼ LC₅ Cu, Pb and Zn) showed the highest bioaccumulation of Cu and Zn in their whole tissue, the most significant increase in AST, ALT & ALP activities and the highest significant levels of total protein, albumin and globulin. Results showed significant alterations in CAT activity in snail tissue extracts while snail samples exposed to most experimental tests showed significant increase in GST activity. Snail samples that exposed to HM mixtures showed a significant decrease in total hemocytes count while snail samples that exposed to mixtures containing A & D showed a significant increase in total hemocytes and Hyalinocytes. Histopathological alterations in snail samples exposed to individual HM and their mixtures for 4 weeks showed degeneration, edema, hyper trophy and vaculation in head-foot muscle, degeneration and necrotic changes in the digestive gland and accumulation in most tested organs. Also, the hermaphrodite gland showed mature ova with irregular shape and reduction in sperm number. In conclusion, the resulted damage and alterations in B. alexandrina studied parameters can be used as bioindicators to the presence of pollutants in its habitats.

Keywords: Biomphalaria, Zn, Cu, Pb, AST, ALT, ALP, total protein albumin, globulin, CAT, histopathology

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Authors: Marina G. Galitskaya, Svetlana G. Makarova, Andrey P. Fisenko.

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Children on medication-induced immunosuppression are at high risk of developing severe course infectious diseases. Therefore, preventive vaccination is especially important for these children. However, due to the immunosuppressive effects of treatment for the underlying disease, the effectiveness of vaccination may decrease below the protective level. In a multidisciplinary children's medical center, post-vaccination immunity was studied in 79 children aged 4-17 years. The children were divided into 2 groups: Group 1 (38 children) with kidney pathology (Nephrotic Syndrome) and Group 2 (41 children) with inflammatory bowel diseases (Ulcerative Colitis, Crohn's Disease). Both groups of children were vaccinated according to the national vaccination calendar and received immunosuppressive therapy (prednisolone, methotrexate, cyclosporine, and other drugs) for at least 1 year. Using the enzyme-linked immunosorbent assay method, specific IgG antibodies to vaccine-preventable infections were determined: measles, rubella, mumps, diphtheria, pertussis, tetanus, and hepatitis B. The study showed the percentage of children with positive IgG values for vaccine-preventable infections. The highest percentage of children had protective antibody levels to measles (84.2% in children with nephrotic syndrome and 92.6% in those with inflammatory bowel disease) and rubella (71% and 80.4%, respectively). The lowest percentage of children with protective antibodies was for hepatitis B (5.2% and 29.2% respectively). Antibodies to mumps, diphtheria, pertussis, and tetanus were found not in all children (from 39,4% to 82,9%). The remaining percentage of children did not have detectable IgG antibodies to vaccine-preventable infections. Not all children, despite the previous vaccination, preserved antibodies to vaccine-controlled infections and remained unprotected by specific IgG antibodies. The issue of a booster vaccine dose should be considered in children without contraindications to vaccination. Children receiving long-term immunosuppressive therapy require an individual vaccination approach, including a specific definition of the performed vaccination.

Keywords: immunosuppressive therapy, inflammatory bowel diseases, nephrotic syndrome, post-vaccination immunity, specific antibodies, vaccine-preventable infections.

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Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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Authors: Matej Patzelt, Jana Mrzilkova, Jan Dudak, Frantisek Krejci, Jan Zemlicka, Zdenek Wurst, Petr Zach, Vladimir Musil

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Introduction: Micro-CT is well used for examination of bone structures and teeth. On the other hand visualization of the soft tissues is still limited. The goal of our study was to elaborate methodology for soft tissue samples imaging in micro-CT. Methodology: We used organs of rats and mice. We either did a preparation of the organs and fixation in contrast solution or we did cannulation of blood vessels and their injection for imaging of the vascular system. First, we scanned native specimens, then we created corrosive specimens by resins. In the next step, we injected vascular system either by Aurovist contrast agent or by Exitron. In the next step, we focused on soft tissues contrast increase. We scanned samples fixated in Lugol solution, samples fixated in pure ethanol and in formaldehyde solution. All used methods were afterwards compared. Results: Native specimens did not provide sufficient contrast of the tissues in any of organs. Corrosive samples of the blood stream provided great contrast and details; on the other hand, it was necessary to destroy the organ. Further examined possibility was injection of the AuroVist contrast that leads to the great bloodstream contrast. Injection of Exitron contrast agent comparing to Aurovist did not provide such a great contrast. The soft tissues (kidney, heart, lungs, brain, and liver) were best visualized after fixation in ethanol. This type of fixation showed best results in all studied tissues. Lugol solution had great results in muscle tissue. Fixation by formaldehyde solution showed similar quality of contrast in the tissues like ethanol. Conclusion: Before imaging, we need to, first, determinate which structures of the soft tissues we want to visualize. In the case of the bloodstream, the best was AuroVist and corrosive specimens. Muscle tissue is best visualized by Lugol solution. In the case of the organs containing cavities, like kidneys or brain, the best way was ethanol fixation.

Keywords: experimental imaging, fixation, micro-CT, soft tissues

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Authors: S. El Ballal, H. El Sabbagh, M. Abd El Gaber, A. Eisa, A. Al Gamal

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Cadmium is one of the most harmful heavy metals able to induce severe injury. In this study, sixty four male Sprague Dawley rats weighing (70-80 gm) were used. Rats were divided into 4 groups each group of 16 rats. Group A: served as control and received commercial ration and distilled water Group B: cadmium chloride was administered orally in water at dose of 300 ppm cadmium (560 mg/L as CdCl2). Group C: Animals received cadmium in drinking water in addition to administration of N-acetylcysteine (NAC) orally at a dose of 150 mg/kg body weight, equivalent to 1500 ppm in food. Group D: Animals received cadmium in drinking water in addition to administration of alpha lipoic acid (ALA) orally at a dose of 150 mg/kg body weight, equivalent to 1500 ppm in food. The experiment was continued for 2 months. Collection of blood and tissue samples was performed at 2, 4, 6, 8 weeks. Blood sample were collected for serum biochemical analysis including malondialdehyde (MDA), total antioxidants, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, urea and uric acid. Tissue specimens were collected for histopathological examination including liver, kidney, brain and testis. Histopathological examination revealed that cadmium choloride induces pathological alterations which increased in severity with time. The use of NAC and ALA can ameliorate toxic effect of CdCl2. The results showed significant decrease MDA and significant increase total antioxidants in group C and D compared to group B, Liver enzymes include AST and ALT showed significant decrease. Regarding to results of total protein and albumin, they revealed significant increase. Urea and uric acid showed significant decrease. From our study we conclude that NAC and ALA have protective effect against cadmium toxicity.

Keywords: ALA, cadmium, histopathology, NAC

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Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar

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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein

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Authors: Mardiana Madjid, Nurpudji Astuti Taslim, Suryani As'ad, Haerani Rasyid, Agussalim Bukhari

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The high level of Urine Urea Nitrogen (UUN) indicates hypercatabolism occurs in hospitalized patients. High levels of Total Lymphocyte Count (TLC) indicates the immune system condition, adequate wound healing, and limit complication. Adequate dietary intake affects to decrease of hypercatabolism status in treated patient’s hospitals. Nitrogen Balance (NB) is simply the difference between nitrogen (N₂) intake and output. If more N₂ intake than output, then positive NB or anabolic will occur. This study aims to evaluate the effect of dietary intake in influencing balance nitrogen and total lymphocyte count. Method: A total of 43 patients admitted to a Wahidin Sudirohusodo Hospital between 2018 and 2019 for 10 days' treats are included. The inclusion criteria were patients who were treated for 10 days and receives food from the hospital orally. Patients did not experience gastrointestinal disorders such as vomiting and diarrhea and experience impair kidney function and liver function and expressed approval to participate in this study. During hospitalization, food intake, UUN, albumin serum, balance nitrogen, and TLC was assessed twice on day 1 and day 10. There is no Physician Clinical Nutritional intervention to correct food intake. UUN is 24 hours of urine collected on the second day after admission and the tenth day. Statistical analysis uses SPSS 24 with observational cohort methods. Result: The Forty-three participants completed the follow-up (27 men and 18 women). The age of fewer than 4 years is 22 people, 45 to 60 years is 16 people, and over 60 years is 4 people. The result of the study on day 1 obtained SGA score A, SGA score B, SGA score C are 8, 32, 3 until day 10 are 8, 31, 4, respectively. According to 24h dietary recalls, the energy intake during observation was from 522.5 ± 400.4 to 1011.9 ± 545.1 kcal/day P < 0.05, protein intake from 20.07 ± 17.2 to 40.3 ± 27.3 g/day P < 0.05, carbohydrates from 92.5 ± 71.6 to 184.8 ± 87.4 g/day, and fat from 5.5 ± 3.86 to 13.9 ± 13.9 g/day. The UUN during the observation was from 6.6 ± 7.3 to 5.5 ± 3.9 g/day, TLC decreased from 1622.9 ± 897.2 to 1319.9 ± 636.3/mm³ value target 1800/mm³, albumin serum from 3.07 ± 0.76 to 2.9 ± 0.57 g/day, and BN from -7.5 ± 7.2 to -3.1 ± 4.86. Conclusion: The high level of UUN needs to correct adequate dietary intake to improve NB and TLC status on hospitalized patients.

Keywords: adequate dietary intake, balance nitrogen, total lymphocyte count, urine urea nitrogen

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Authors: Rima Al Garni, Emad Al Shdaifat, Sahar Elmetwalli, Mohammad Alzaid, Abdulrahman Alghothayyan, Sara Al Abd Al Hai, Seham Al Rashidi

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Aim: To investigate the prevalence of non-adherence of patients on haemodialysis and explore their perception of the importance of adherence to the therapeutic regime and estimate the predictors for adherence to the therapeutic regime. Background: End-stage renal disease is commonly treated by haemodialysis. Haemodialysis treatment alone is not effective in replacing kidney function. Diet and fluid restrictions, along with supplementary medications, are mandatory for the survival and well-being of patients. Hence, adherence to this therapeutic regimen is essential. However, non-adherence to diet and fluid restrictions, medications, and dialysis is common among patients on haemodialysis. Design: Descriptive cross-sectional method was applied to investigate the prevalence of non-adherence to treatment, including adherence to diet and fluid restrictions, medications, and dialysis sessions. Methods: Structured interviews were conducted using the Arabic version of the End-Stage Renal Disease Adherence Questionnaire. The sample included 230 patients undergoing haemodialysis in the Eastern Region of Saudi Arabia. Data were analysed using descriptive statistics and multiple regressions. Results/Findings: Most patients had good adherence (71.3%), and only 3.9% had poor adherence. The divorced or widowed patient had higher adherence compared with single (P=0.011) and married participants (P=0.045) through using the post hoc test. Patients above 60 years had higher adherence compared to patients below 40 years old (P=0.016) using the post hoc test. For the perception of the importance of adherence to the therapeutic regime subscale, two-thirds of the patients had lower scores (<=11). Conclusion: Adherence to therapeutic regime is high for three fourth of patients undergoing haemodialysis in the Eastern Region of Saudi Arabia; this finding is similar to results abstracted from the local literature. This result would help us highlight the needs of patients who are not compliant with their treatment plans and investigate the consequences of non-adherence on their well-being and general health. Hence, plan individualised therapeutic programmes that could raise their awareness and influence their adherence to therapeutic regimes.

Keywords: adherence to treatment, haemodialysis, end stage renal disease, diet and fluid restrictions

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Authors: Arman Kishan, Sanjay Kubsad, Steve Li, Mark Haft, Duc Nguyen, Dawn Laporte

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Objective: Carpal tunnel syndrome can be managed surgically with endoscopic or open carpal tunnel release (CTR). Rheumatoid arthritis (RA) is a known risk factor for Carpal Tunnel Syndrome (CTS) and is believed to be related to compression of the median nerve secondary to inflammation. We aimed to analyze national trends, outcomes, and patient-specific comorbidities associated with ECTR and OCTR in patients with RA. Methods: A retrospective cohort study was conducted using the PearlDiver database, identifying 683 RA patients undergoing ECTR and 4234 undergoing OCTR between 2010 and 2014. Demographic data, comorbidities, and complication rates were analyzed. Univariate and multivariable analyses assessed differences between the treatment methods. Results:  Patients with RA undergoing ECTR in comparison to OCTR had no significant differences in medical comorbidities such as hypertension, obesity, chronic kidney disease, hypothyroidism and diabetes mellitus. Patients in the ECTR group reported a risk ratio of 1.44 (95%CI: 1.10-1.89, p=0.01) of requiring repeat procedures within 90 days of the initial procedure. Five-year trends in ECTR and OCTR procedures reported a combined annual growth rate of 5.6% and 13.15, respectively. Conclusion: Endoscopic and open approaches to CTR are important considerations in surgical planning. RA and ECTR have previously been identified as independent risk factors for revision CTR. Our study has identified the 90-day risk of repeat procedures to be elevated in the ECTR group in comparison to the OCTR group. Additionally, the growth of OCTR procedures has outpaced the growth of ECTR procedures in the same period, likely in response to the trend of ECTR leading to higher rates of repeat procedures. The need for revision following ECTR in patients with RA could be related to chronic inflammation leading to transverse carpal ligament thickening and concomitant tenosynovitis. Future directions could include further characterization of repeat procedures performed in this subset of patients. 

Keywords: endoscopic treatment of carpal tunnel syndrome, open treatment of carpal tunnel syndrome, rheumatoid arthritis, trends analysis, carpal tunnel syndrome

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Authors: David C. Boettiger, Tracy Kuo Lin, Maram Almansour, Mariam M. Hamza, Reem Alsukait, Christopher H. Herbst, Nada Altheyab, Ayman Afghani, Faisal Kattan

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Background The number of people aged greater than 65 years per 100 people aged 20–64 years is expected to almost double in The Kingdom of Saudi Arabia (KSA) between 2020 and 2030. We therefore aimed to quantify the growing non-communicable disease (NCD) burden in KSA between 2020 and 2030, and the impact this will have on the national health budget. Methods Ten priority NCDs were selected: ischemic heart disease, stroke, type 2 diabetes, chronic obstructive pulmonary disease, chronic kidney disease, dementia, depression, osteoarthritis, colorectal cancer, and breast cancer. Age- and sex-specific prevalence was projected for each priority NCD between 2020 and 2030. Treatment coverage rates were applied to the projected prevalence estimates to calculate the number of patients incurring treatment costs for each condition. For each priority NCD, the average cost-of-illness was estimated based on published literature. The impact of changes to our base-case model in terms of assumed disease prevalence, treatment coverage, and costs of care, coming into effect from 2023 onwards, were explored. Results The prevalence estimates for colorectal cancer and stroke were estimated to almost double between 2020 and 2030 (97% and 88% increase, respectively). The only priority NCD prevalence projected to increase by less than 60% between 2020 and 2030 was for depression (22% increase). It is estimated that the total cost of managing priority NCDs in KSA will increase from USD 19.8 billion in 2020 to USD 32.4 billion in 2030 (an increase of USD 12.6 billion or 63%). The largest USD value increases were projected for osteoarthritis (USD 4.3 billion), diabetes (USD 2.4 billion), and dementia (USD 1.9 billion). In scenario analyses, our 2030 projection for the total cost of managing priority NCDs varied between USD 29.2 billion - USD 35.7 billion. Conclusions Managing the growing NCD burden in KSA’s aging population will require substantial healthcare spending increases over the coming years.

Keywords: aging, non communicable disease, costs, Saudi Arabia

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Authors: Sunghee Nam

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Entomopathogenic fungi is a Cordyceps species that is isolated from dead silkworm and cicada. Fungi on cicadas were described in old Chinese medicinal books and from ancient times, vegetable wasps and plant worms were widely known to have active substance and have been studied for pharmacological use. Among many fungi belonging to the genus Cordyceps, Cordyceps sinensis have been demonstrated to yield natural products possessing various biological activities and many bioactive components. Generally, It is commonly used to replenish the kidney and soothe the lung, and for the treatment of fatigue. Due to their commercial and economic importance, the demand for Cordyceps has been rapidly increased. However, a supply of Cordyceps specimen could not meet the increasing demand because of their sole dependence on field collection and habitat destruction. Because it is difficult to obtain many insect hosts in nature and the edibility of host insect needs to be verified in a pharmacological aspect. Recently, this setback was overcome that P. tenuipes was able to be cultivated in a large scale using silkworm as host. Pharmacological effects of P. tenuipes cultured on silkworm such as strengthening immune function, anti-fatigue, anti-tumor activity and controlling liver etc. have been proved. They are widely commercialized. In this study, we attempted to establish a method for stable growth inhibition of P. tenuipes on silkworm hosts and an optimal condition for synnemata formation. To determine optimum culturing conditions, temperature and light conditions were varied. The length and number of synnemata was highest at 25℃ temperature and 100~300 lux illumination. On an average, the synnemata of wild P. tenuipes measures 70 ㎜ in length and 20 in number; those of the cultured strain were relatively shorter and more in number. The number of synnemata may have increased as a result of inoculating the host with highly concentrated conidia, while the length may have decreased due to limited nutrition per individual. It is not able that changes in light illumination cause morphological variations in the synnemata. However, regulation of only light and temperature could not produce stromata like perithecia, asci, and ascospores.

Keywords: optimization of culture conditions of paecilomyces tenuipes, entomopathogenic fungi optimization of culture conditions of paecilomyces tenuipes, entomopathogenic fungi silkworm larva, bombyx mori

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