Insulin Growth Factor-1 in Egyptian Children with Juvenile Idiopathic Arthritis: Correlation with Growth Pattern and Disease Activity

Background: Juvenile idiopathic arthritis (JIA) is a systemic, chronic, inflammatory disease that affects patients under 18 years. Interactions between growth hormone (GH), insulin-like growth factor-1 (IGF-1), and the immune system are complex. Many studies found that chronic inflammation suppresses GH/IGF-1 axis.Objective: To assess if there is correlation between the serum level of IGF-1 and the growth pattern in children with JIA in Egypt, and to evaluate the correlation between the serum level of IGF-1 and disease activity among these patients. Patients and Method: The study was a case control study which included 80 patients with JIA and 40 normal children as a control. Their ages ranged from 5-15 years. All patients were subjected to full history taking from their care givers, clinical examination, growth assessment, and laboratory measurement of serum IGF-1 level, CRP, ESR, and CBC.Results: There was a statistically significant decrease in serum level of IGF-1 among patients with JIA. There was a statistically significant positive correlation between serum level of IGF-1 with height, weight and BMI. There was a statistically significant difference between patients and controls regarding Height-for-Age-Z-Score (HAZ), 35% of patients had short stature. There was a statistically significant decrease in weight and BMI, 90% of patients were underweight. There was no statistically significant correlation between serum level of IGF-1 and the disease activity. Conclusion: There was a statistically significant positive correlation between IGF-1 with height, weight and BMI. Short stature and underweight were common among JIA patients. There was no significant correlation between serum level of IGF-1 and the disease activity among JIA patients

Saponinas de aceite de camelia: extracción en fase sólida y su efecto en sangre y órganos de ratones

In this study, the tea saponin extracted experiment was adopted to optimize extraction conditions. The solid phase extraction technique was used to extract saponin from camellia tea oil. Four macro-porous resins (DM301; NKA-9; HZ-841; S-8), two cation exchange resins (D001; 732), chitosan and diatomite, respectively, were used in a preliminary experiment; the HZ-841 macro-porous resin was determined as the optimal solid adsorbent material. The extraction conditions were; temperature 23.78 ºC; adsorption time 5.20 hour; liquid-to-solid ratio 12.54:1; predicted adsorption rate 20.20%; ethanol concentration 83.27%; eluent flow rate 1.18 mL/min; liquid-to-solid ratio 21.85:1; and the elution rate of tea saponin was calculated as 59.55%. The effect of tea seed oil saponin on mice blood and organs (liver, kidney, spleen and heart) was studied. The mice were randomly divided into six groups and fed for 90-days. Their weights were recorded every day. On the last day of the experiment serum ele­ments: Total cholesterol (TC), triglycerides (TG), low and high-density lipoproteins (LDL, HDL), as well as AST (aspartate aminotransferase), ALT (alanine aminotransferase) and total protein (TP) and organ (liver, kidney, spleen and heart) histopathologies were determined. The study results demonstrated that tea oil saponin expanded TC, TG, LDL and HDL. However, it generally increased ALT, AST activities and TP values compared to control groups. Tea oil saponin had no effect on organ tissue histopathology compared to control groups.En este estudio se optimizaron las condiciones de extracción de las saponina de té. La técnica de extracción en fase sólida se utilizó para extraer la saponina del aceite de té de camelia. Se utilizaron cuatro resinas macropo­rosas (DM301; NKA-9; HZ-841; S-8), dos resinas de intercambio catiónico (D001; 732), quitosán y diatomita, respectivamente, en un experimento preliminar. La resina macroporosa HZ-841 se determinó como el material adsorbente sólido óptimo. Las condiciones de extracción fueron: temperatura de 23,78 ºC, tiempo de adsorción de 5,20 horas, relación líquido:sólido: 12,54:1; tasa de adsorción prevista: 20,20%; concentración de etanol: 83,27%, el flujo de eluyente de 1,18 ml/min, relación de líquido:sólido de 21,85:1, y la velocidad de elución de la saponina del té se calculó como 59,55%. Se estudió el efecto de la saponina del aceite de semilla de té en la sangre y los órganos de los ratones (hígado, riñón, bazo y corazón). Los ratones se dividieron al azar en seis grupos y se alimentaron durante 90 días, y se registraron sus pesos todos los días. En el último día del experimento se detectaron histopatología en los elementos séricos: colesterol total (TC), triglicéridos (TG), lipoproteínas de baja y alta densidad (LDL, HDL), AST, ALT y proteína total (TP) y órganos (hígado, riñón, bazo y corazón). Los resultados del estudio demostraron que las saponinas del aceite de té aumentaron el TC, TG, LDL y HDL. Sin embargo, también en general aumentó las actividades de ALT, AST y los valores de TP en comparación con los grupos de control. Las saponinas del aceite de té no tuvieron efecto sobre la histopatología de tejidos de los órganos en comparación con los grupos de control

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Postoperative complications after pancreatoduodenectomy for malignancy: results from the Recurrence After Whipple’s (RAW) study

Background Pancreatoduodenectomy (PD) is associated with significant postoperative morbidity. Surgeons should have a sound understanding of the potential complications for consenting and benchmarking purposes. Furthermore, preoperative identification of high-risk patients can guide patient selection and potentially allow for targeted prehabilitation and/or individualized treatment regimens. Using a large multicentre cohort, this study aimed to calculate the incidence of all PD complications and identify risk factors. Method Data were extracted from the Recurrence After Whipple’s (RAW) study, a retrospective cohort study of PD outcomes (29 centres from 8 countries, 2012–2015). The incidence and severity of all complications was recorded and potential risk factors for morbidity, major morbidity (Clavien–Dindo grade > IIIa), postoperative pancreatic fistula (POPF), post-pancreatectomy haemorrhage (PPH) and 90-day mortality were investigated. Results Among the 1348 included patients, overall morbidity, major morbidity, POPF, PPH and perioperative death affected 53 per cent (n = 720), 17 per cent (n = 228), 8 per cent (n = 108), 6 per cent (n = 84) and 4 per cent (n = 53), respectively. Following multivariable tests, a high BMI (P = 0.007), an ASA grade > II (P II patients were at increased risk of major morbidity (P < 0.0001), and a raised BMI correlated with a greater risk of POPF (P = 0.001). Conclusion In this multicentre study of PD outcomes, an ASA grade > II was a risk factor for major morbidity and a high BMI was a risk factor for POPF. Patients who are preoperatively identified to be high risk may benefit from targeted prehabilitation or individualized treatment regimens

Discovery of potential natural dihydroorotate dehydrogenase inhibitors and their synergism with brequinar via integrated molecular docking, dynamic simulations and in vitro approach

AbstractThe critical function of dihydroorotate dehydrogenase (DHODH) in pyrimidine synthesis attracted a great interest throughout beyond decades. Inhibitors of human DHODH (hDHODH) have validated efficacy for remedy of many immunological diseases. Brequinar and leflunomide are examples of such compounds. However, most of such immunosuppressive medications suffer from a lot of side effects and accompanied by adverse metabolic disturbances and toxicities. So that, immunomodulation utilizing natural products received the attention of many researchers. In this study, computer-aided molecular docking, molecular dynamic (MD) simulations and biochemical testing were utilized to find new pharmacologically active chemical entities from natural sources to combat immunosuppressive diseases. More specifically, Glide docking was used for a structure-based virtual screening of in-house 3D database of compounds retrieved from some traditionally known immunomodulatory plants surveyed from literature. The top five scored plants were found to be Zingiber officinale, Curcuma longa, Glycyrrhiza glabra, Allium sativum and Olea europaea. In vitro hDHODH inhibitory assays illustrated the ability of Allium sativum and silymarin standard hits; specifically, silibinin, to significantly inhibit the hDHODH enzyme. Molecular docking and MD simulations revealed a strong binding of the discovered hits within the active site. Following that, the most promising hits were tested separately with brequinar in a fixed-ratio combination setting to assess their combined effects on hDHODH catalytic inhibition. The binary combination of silibinin and brequinar revealed that in this combination, brequinar could be utilized at a dose 9.33-fold less when compared to its single-use to produce 99% inhibition for hDHODH enzyme. These findings confirmed that this binary mixture is an excellent combination providing better therapeutic effects and lower side effects.</jats:p

Amarbellisine, a lycorine-type alkaloid from Amaryllis belladonna L. growing in Egypt

A new lycorine-type alkaloid, named (-)-amarbellisine (I), was isolated from the bulbs of Egyptian Amaryllis belladonna L. together with the well known alkaloids (-)-lycorine, (-)-pancracine, (+)-vittatine, (+)-11-hydroxyvittatine, and (+)-hippeastrine. The new alkaloid, contg. the pyrrolo[de]phenanthridine ring system, was essentially characterized by spectroscopic and optical methods, and proved to be the 2-methoxy-3a,4,5,7,11b,11c-hexahydro-1H-[1,3]dioxolo[4,5-j]pyrrolo[3,2,1-de]phenanthridinol. By using HPTLC technique we also carried out a comparative study of the relative and total alkaloidal content at two different stages of plant growth. Finally, the antimicrobial activity of the isolated alkaloids was assaye