Normal Dosage Research Articles

Flavonoid-rich extract from Citrullus lanatus (Watermelon) seed attenuated Ethanol-Induced Kidney injury in Wistar Rats

BackgroundEthanol intake can cause oxidative stress, tissue inflammation, and renal damage by producing free radicals. Flavonoids are phenolic chemicals found in a range of fruits, vegetables, tea, and wine. More significantly, many flavonoids are active constituents in traditional Chinese herbal medicines, which have no adverse effects in general. However, there is a paucity of research on the therapeutic effectiveness of Citrullus lanatus seed flavonoids against renal damage. MethodThe rats were split into six groups: normal, ethanol (10 ml/kg of 50% ethanol), flavonoids (100 mg/kg/day), ethanol plus low and high flavonoid dosages (ET + 100 and 200 mg/kg FCL), and ethanol plus Silymarin (ET + 100 mg/kg SLY). The levels of serum urea, creatinine, uric acid, and nitrite oxide (NO) were measured, as were oxidative stress markers such as superoxide dismutase (SOD), catalase (CAT), glutathione (GPx), malondialdehyde (MDA), and inflammatory markers such as tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). Then, the kidney organ was harvested for histological study. ResultsCitrullus lanatus seed flavonoids (FCL) substantially (p < 0.05) reduced ethanol-induced increases in creatinine, urea, and uric acid. When rats administered FCL were compared to untreated ethanol rats, there was a significant increase (p < 0.05) in CAT, SOD, and GPx levels, as well as decreased MDA. FCL significantly reduced IL-1β and TNF-α levels in ethanol-treated rats. A histological examination significantly corroborated the biochemical assay result. ConclusionsThe findings of this study show that the flavonoid-rich fraction of Citrullus lanatus seed has therapeutic potential against ethanol-induced kidney injury by lowering the rise in renal function, inflammatory markers, and oxidative stress. As a result, FCL may work as a plant-based natural therapy to minimise kidney damage. As a result, in the preclinical context, FCL has the potential to minimise organ toxicity for oral therapeutic purposes.

Enhancing Grain Yield and Zinc Content in Bread Wheat Using Zinc and Nitrogen Application under Supplementary Irrigation Treatments

Wheat (Triticum aestivum L.) is one of the crops that has great importance in human and animal nutrition. Nutrient management can improve the nutritional value and grain yield in bread wheat. Therefore, this study was conducted to assessment the effect of Zinc (Zn) levels as well as the interactions with Nitrogen (N) and irrigation regimes on yield, yield components and Zn content in bread wheat grain. To this purpose, an experiment was performed in a split-split plot design with four replications, which supplementary irrigation (no irrigation, irrigation at stem elongation and irrigation at the stage of grain filling) as the main plot, Zn levels as split-plot (no spraying of Zn and Spraying Zn with a concentration of 5%) and nitrogen consumption levels (nitrogen-free, half the normal dosage and normal nitrogen consumption) as split-split factors. The results showed that the grain yield and yield components affected by the applied treatments. The highest grain yield (646 g/m2 ) and Zn concentration (32.69%) observed in spraying Zn at 5% concentration supplemented with irrigation at the grain filling stage with normal N application. Also, Zn content of grain was increased by Zn foliar application. Furthermore, the grain yield significantly correlated with Zn content, Harvest index (HI), seed filling rate (SFR), thousand seed weight (TKW) and seed number per spike (SNS) traits. The highest grain yield was obtained in supplementary irrigation in grain filling stage indicating importance of supplementary irrigation in this stage. In general, the results of this study showed that the grain yield and quality in bread wheat could be increased by supplementary factors.

Role of hemoperfusion combined with hemodialysis in acute severe organophosphorus pesticide poisoning: a meta-analysis

Abstract Background Acute severe organophosphorus pesticide poisoning is a common severe emergency in developing countries. Our meta-analysis aimed to clarify the efficacy of hemoperfusion combined with hemodialysis on acute severe organophosphorus pesticide poisoning. Methods Several databases were searched. After formulating relevant inclusion and exclusion criteria, qualified studies were included, and the data were extracted. The outcome indicators were the success rate of rescue, the time of hospitalization, the incidence of complications, the time for the cholinesterase level to return to normal, the coma time, and the atropine dosage. The results were analyzed using risk ratios, weighted mean difference, standard mean difference, and 95% confidence interval. The Cochrane Collaboration tool was used to assess the risk of bias in all the included studies. In terms of statistical methods, we used RevMan software (version 5.3; The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) and Stata (versions 14 and 16; StataCorp, College Station, TX, USA) for the data analysis. Results We included 92 randomized controlled trials with 6899 participants. Compared with the conventional emergency treatment group (CET group), the hemoperfusion group (HP + CET group), and the hemodialysis group (HD + CET group), the use of hemoperfusion combined with hemodialysis based on CET (HP + HD + CET group) significantly increased the success rate of rescue and reduced hospitalization time, the incidence of complications, time for cholinesterase level to return to normal, coma time, and atropine dosage. Conclusion Hemoperfusion combined with hemodialysis is effective in the treatment of acute severe organophosphorus pesticide poisoning. In the future, more scientifically designed, large-scale, high-quality, multicenter randomized controlled trials are needed to validate this study further.

Étude Transversale sur les Effets Indésirables de la Chlorhydrate de Métformine chez 130 Patients Diabétiques Type 2 Admis au Centre Médical et à la Maison du Diabète de Sidi Bel-Abbès

MetforminHydrochloride is an antidiabetic used for many years, currently; it considered the first choice in treatment of type 2 diabetes (T2D). It decreases insulin resistance, does not induce hypoglycaemia, increases glucose utilization in the liver and skeletal muscle, and decreases hepatic glucose production. Its adverse effects (AE) are gastrointestinal, decrease in vitamin B12 absorption, abnormalities of hemogram and rarely skin reactions. The objective of this study was to report the type and frequency of AEs of Metformin Hydrochloride used in the therapeutic management of T2D patients admitted to the medical center and the diabetes home of Sidi Bel-Abbès in Algeria. A cross-sectional descriptive study was carried out over a period of four months, from January 1st, 2017 to April 30th, 2017, involving 130 patients treated with Metformin Hydrochloride consulting at Mimoun City Diabetes Home and Gambetta Diabetes Center in the town of Sidi Bel-Abbès. The primary outcome measure was the determination of the type and frequency of AEs related to normal dosages or overdose use of Metformin Hydrochloride in T2D. Data were collected from patient records, using a questionnaire, and analyzed using Statistical Package for the Social Sciences, version 20 software. 130 patients were included, including 82 women, with a mean age of 51.08±8.85 years (30-66). One hundred and ninety-eight (198) AEs were reported, an average of 1.52 AEs per patient. Among them, 95 (47.98%) AEs are digestive disorders (30.77% of patients suffered from diarrhea, 10.77% had nausea and vomiting, 8.46% suffered from abdominal pain and bloating, 3.85% lost their taste, 7.69% complained of epigastric cramps and 11.54% of anorexia), 29 (14.65%) AEs are hypoglycaemia, 73 (36.87%) AEs are other symptoms and 1 (0.50%) EI is vitamin B12 deficiency and no cases of lactic acidosis or allergic reaction were reported. Five (3.85%) patients had a total and lasting intolerance to Metformin Hydrochloride leading to its discontinuation following persistent diarrhoea. AEs of Metformin Hydrochloride used in the management of T2D patients consulting at the medical center and the Diabetes home of Sidi Bel-Abbès are frequent. Digestive disorders were the most frequent, diarrhea was very frequent and led to discontinuation of treatment in 3.85% of T2D patients, followed by nausea and vomiting, then abdominal pain, bloating and epigastric cramps, and rarely taste metallic. Hypoglycaemia was frequent following its association with insulin, the onset of headaches and fatigue were frequent, but no case of lactic acidosis or allergic reaction was reported. Due to a lack of means, the dosage of homocysteine and methylmalonic acid had not been carried out to confirm the vitamin B12 deficiency in the patient whose level was less than 200ng/mL. A precise assessment of the imputability of reported AEs is necessary.

De-erosion of X chromosome dosage compensation by the editing of XIST regulatory regions restores the differentiation potential in hPSCs

Human pluripotent stem cells (hPSCs) regularly and irreversibly show the erosion of X chromosome inactivation (XCI) by long non-coding RNA (lncRNA) XIST silencing, causing challenges in various applications of female hPSCs. Here, we report reliable methods to reactivate XIST with monoallelic expression in female hPSCs. Surprisingly, we find that the editing of XIST regulatory regions by Cas9-mediated non-homologous end joining is sufficient for the reactivation of XIST by endogenous systems. Proliferated hPSCs with XIST reactivation show XCI from an eroded X chromosome, suggesting that hPSCs with normal dosage compensation might lead to a growth advantage. Furthermore, the use of targeting vectors, including the XIST regulatory region sequences and selection cassette, enables XIST reactivation in hPSCs with high efficiency. XIST-reactivated hPSCs can show the restoration of differentiation potential. Thus, our findings demonstrate that XIST re-expression is a beneficial method to maximize the use of female hPSCs in various applications, such as proper disease modeling.

S3300 Acetaminophen Toxicity Amplified: Drug-Induced Liver Injury in a Malnourished Patient

Introduction: Acetaminophen toxicity is a leading cause of acute liver injury and failure in the U.S. Excess acetaminophen results in formation of N-acetyl-p-benzoquinoneimine (NAPQI) which causes irreversible oxidative hepatocyte injury and cell necrosis. Treatment with N-acetylcysteine (NAC) replenishes glutathione stores which inactivate NAPQI. In a healthy adult, acetaminophen doses less than 4 g per 24 hours are considered safe. Toxicity from therapeutic doses of acetaminophen, in the setting of malnourishment, has been rarely reported and is presented here. Case Description/Methods: A 37-year-old female with a history of gastroparesis and chronic malnutrition was admitted for elevated liver enzymes on routine blood work. She reported symptoms of fatigue, nausea, and poor oral intake from suspected gastroparesis. She also admitted to taking 1300 mg of acetaminophen intermittently during the past week for myalgias. Exam revealed normal mentation without evidence of hepatic encephalopathy (HE), cachexia with a BMI of 15.2, and mild epigastric and left upper quadrant tenderness. Laboratory data (36 hours after last ingestion of acetaminophen) revealed an ALT of 1180 u/L, AST of 1950 u/L, ALP of 121 u/L, total bilirubin of 2.7 mg/dL, direct bilirubin of 2.5 mg/dL and INR of 1.6. Her acetaminophen level was 15.8 mcg/mL. A liver ultrasound was unremarkable. NAC was subsequently administered as per protocol 21 hour infusion. She was ruled out for other etiologies of acute liver injury. She never developed HE and her liver enzymes, along with INR, normalized at discharge. Discussion: This case highlights the lower threshold for toxicity of acetaminophen in a malnourished patient. In previous case reports, acetaminophen doses less than 2 g per 24 hours are listed as being safe in a nutritionally deficient patient. Our case questions this assertion given our patient ingested 65% of this amount. Evidence in the relatively limited pool of literature suggests that malnourished patients generally have low stores of glutathione, thereby limiting the metabolic clearance of acetaminophen ingested even at normal dosages, amplifying total acetaminophen levels, and leading to increased NAPQI. Prospective study is limited to rat models and single case reports. Fortunately, our patient was promptly treated with NAC and did not progress to liver failure. This case highlights the narrow therapeutic window of acetaminophen in malnourished patients, one that warrants close observation by clinicians.

A comparative study of vestibular improvement and gastrointestinal effect of betahistine and gastrodin in mice

Betahistine and gastrodin are the first-line medications for vestibular disorders in clinical practice, nevertheless, their amelioration effects on vestibular dysfunctions still lack direct comparison and their unexpected extra-vestibular effects remain elusive. Recent clinical studies have indicated that both of them may have effects on the gastrointestinal (GI) tract. Therefore, we purposed to systematically compare both vestibular and GI effects induced by betahistine and gastrodin and tried to elucidate the mechanisms underlying their GI effects. Our results showed that betahistine and gastrodin indeed had similar therapeutic effects on vestibular-associated motor dysfunction induced by unilateral labyrinthectomy. However, betahistine reduced total GI motility with gastric hypomotility and colonic hypermotility, whereas gastrodin did not influence total GI motility with only slight colonic hypermotility. In addition, betahistine, at normal dosages, induced a slight injury of gastric mucosa. These GI effects may be due to the different effects of betahistine and gastrodin on substance P and vasoactive intestinal peptide secretion in stomach and/or colon, and agonistic/anatgonistic effects of betahistine on histamine H1 and H3 receptors expressed in GI mucosal cells and H3 receptors distributed on nerves within the myenteric and submucosal plexuses. Furthermore, treatment of betahistine and gastrodin had potential effects on gut microbiota composition, which could lead to changes in host-microbiota homeostasis in turn. These results demonstrate that gastrodin has a consistent improvement effect on vestibular functions compared with betahistine but less effect on GI functions and gut microbiota, suggesting that gastrodin may be more suitable for vestibular disease patients with GI dysfunction.

Wheat Yield Modelling using Infocrop and DSSAT Crop Simulation Models

Background: Wheat is an important crop of India That is grown in the winter season (October to April). A field study was conducted for nine plots having a dimension of 3 × 2 meter and different nutrient was applied to test the biomass yield. The objectives are to describe (a): To conduct field experiments under controlled conditions and vary the dosage of fertilizers for different treatments. (b): To observe the variation in crop yield of wheat with different dosages of fertilizers. (c): To model the crop yield of different treatments using InfoCrop and DSSAT crop models. Methods: An experiment was conducted for Wheat crop having a dimension of 3 × 2 meter at the Indian Institute of Technology, UK-India. Three plots (C1, C2, C3) was given control fertilizer supply while plot (F1, F2, F3) given -25%, +25%, +50% and plot (N1, N2, N3) given -25%, +25%, +50% w.r.t to control. The simulation model Infocrop and DSSAT were simulated to check test the model. Result: In this study, two crop simulation models namely Infocrop and DSSAT were used to predict the yield of wheat crops. Field experiments were carried out at a farm site at Roorkee, India and different treatments of fertilizers are applied to the field plots. In total, seven fertilizer treatments are used: C (controlled with a normal dosage of fertilizers), F1, F2, F3 (varying amount of applied farmyard manure), N1, N2 and N3 (varying amount of applied urea). The objective of the study was to evaluate yields of the seven treatments using Infocrop and DSSAT crop models and compare them to the observed values of yields. The grain yield of the controlled treatment (C1, C2, C3) was predicted accurately by both models. There was a significant variation in the grain yields of the F1, F2, F3 treatments with the application of farm yard manure (FYM). DSSAT under-predicted the grain yields for the plot F1, F2, F3 treatments and over-predicted these for N1, N2, N3 treatments. Overall, Infocrop, which was developed and validated for Indian conditions, simulated the grain yield more accurately as compared to the DSSAT model under varying applications of FYM and urea dosages.

Immunogenicity and safety of double dosage of pneumococcal vaccines in adult kidney transplant recipients and waiting list patients: A non-blinded, randomized clinical trial

BackgroundPneumococcal prime-boost vaccination is recommended for solid organ transplant recipients, but is not thoroughly tested in this population. Furthermore, a pneumococcal vaccine dose effect has never been investigated, though observed in healthy adults. To assess whether a double dose of 13-valent pneumococcal conjugate vaccine (PCV13) and of 23-valent pneumococcal polysaccharide vaccine (PPV23) increases the immunogenicity of prime-boost vaccination in kidney transplant recipients (KTRs) and patients on the kidney transplant waiting list (WLPs), a phase 3, randomized, non-blinded trial was conducted. MethodsKTRs and WLPs were in parallel groups assigned either normal or double dosage of both vaccines 12 weeks apart. A ′protective response′ was an average geometric mean concentration ≥ 1 mg/L based on 12 vaccine shared serotype-specific IgG antibodies. Furthermore, number of antibodies with ≥ 2-fold rises and individual serotype-specific antibody concentrations were evaluated. Follow-up was 48 weeks. ResultsSeventy-four KTRs and 65 WLPs were enrolled. In WLPs, double dosage resulted in a significantly higher proportion of participants with a ′protective response′ (66.7%), 5 weeks after PPV23, compared to normal dosage (35.5%), p = 0.015. KTRs exhibited no dose effect. After PPV23, all four groups had increased their number of serotypes with ≥ 2-fold rises (p ≤ 0.05 for both WLPs groups; p ≤ 0.01 for both KTRs groups). Vaccines were safe, well tolerated and still immunogenic at week 48. ConclusionsData suggests that double dosage of pneumococcal vaccines used according to the prime-boost strategy might be recommendable for WLPs. Furthermore, our data supports PPV23́s additive effect to PCV13 in KTRs and WLPs. (EudraCT: 2016–004123-23)

MO229: Is Nodular Glomerulosclerosis Always Associated with Diabetic Nephropathy?

Abstract BACKGROUND AND AIMS Nodular glomerulosclerosis (NGS) is a histological diagnosis that can be found in several etiologies. It corresponds to a particular form of expansion of the extracellular matrix within the mesangium. Glomerulosclerosis is not very specific, its nodular form is on the other hand more interesting from an etiological point of view since only a few pathologies can take this aspect, the most frequent are diabetes (mainly), membranoproliferative glomerulonephritis (MPGN) and renal expression of gammopathies monoclonal. In the absence of an identified etiology, NGS is said to be idiopathic. This entity, described 30 years ago, is very rare and therefore largely unrecognized. Some pathophysiological hypotheses have emerged in recent years, particularly involving smoking, high blood pressure or insulin resistance. The aims of our study were as follows: METHOD Monocentric retrospective study of patients with NGS in renal biopsy, collected between January 2016 and December 2021 at Mohammed VI University hospital of Marrakech. The epidemiological, clinical and etiological characteristics were studied. RESULTS We have collected 108 NGS. Of our patients, 47.22% presented with NGS of diabetic origin and 52.95% with non-diabetic NGS. For patients with NGS of diabetic origin, the indication for PBR was glomerular syndrome (19 patients), nephrotic syndrome (7 patients), rapidly progressive renal failure or severe renal failure (11 patients), recent diabetes (7 patients), absence of diabetic retinopathy (3 patients), presence of extra-renal signs (2 patients) and monoclonal peak (2 patients). The diagnosis of idiopathic NGS was made after eliminating all the etiologies of NGS (normal complement dosage, no diabetes, no monoclonal peak, negative IFD, history of smoking and hypertension and dyslipidemia) and immunohistochemistry. Two patients were tested for deposits of the kappa and lambda chains, thus eliminating the myeloma. Among the risk factors for idiopathic SNB detected in our work, we cite: CONCLUSION The most common etiology of NGS remains diabetes, but this lesion can be seen in other conditions such as MPGN, Randall disease, amyloidosis, monotypic immunoglobulin deposition, non-immunoglobulin and idiopathic glomerulopathies. Idiopathic nodular glomerulosclerosis is a rare entity, frequent in most series in humans, which contrasts with the data of our study. On the other hand, a causal link between this histological entity and smoking, hypertension and Metabolic syndrome has been well established in several studies, which is consistent with the data from our work.

Development of a detector tube for rapid detection of tadalafil in adulterated dietary supplements

ABSTRACT Introduction Products marketed as dietary supplements for improving sexual performance at times include phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil and analogues. The ingestion of these dietary supplements is extremely dangerous as these are not evaluated for their efficacy and safety as pharmaceuticals, and their manufacture is not controlled. For this reason, regulatory authorities conduct inspections on these products to prevent the occurrence and spread of health hazards. Tadalafil is one of the PDE5 inhibitors, and its analogues are found as the most major adulterants in sexual products after analogues of sildenafil. Tadalafil has two chiral carbons that are both R configuration, which is important for PDE5 inhibitory activity. To confirm the molecular configuration of the tested compound, it is subject to instrumental analysis such as circular dichroism detection or X-ray crystal structure analysis. Therefore, it takes longer for testing tadalafil than for other compounds that do not require these processes. Meanwhile, in 2020, the product containing 120 times more tadalafil than the normal dosage was detected in Tokyo, making it an urgent issue to remove these dangerous products from the market. This study proposes a simple and rapid method to detect tadalafil with a newly devised detector tube. Objective Development of a detector tube for the rapid screening of tadalafil with simple functioning. Methods Approximately 80 mg of silica gel powder impregnated with sulfuric acid was filled in a glass tube, having a 3-mm inner diameter, to prepare a detector tube. The measuring method of this detector tube is quite simple; first, both tips of the detector tube are cut, then the sample solution is aspirated, and a decision is made by the colour of the detector tube after 5 minutes. It was defined as a positive result when the detector tube turned violet and negative when it showed other colours. First, the reaction of tadalafil and analogues were confirmed using the prepared detector tube. Then, specificity was tested for active pharmaceutical ingredients and common additives. The tube was also tested for the applicability to some commercially available dietary supplements. Results All tested tadalafil and analogues showed positive results in the test. The limit of detection was 5 μg/mL for tadalafil. Except for levomepromazine, results for additives and any pharmaceutical ingredients tested were negative. This tube was able to detect all real samples containing tadalafil and analogues. None of the real samples that did not contain tadalafil and analogues gave false positives. Conclusions The developed detector tube could rapidly detect tadalafil and analogues with high sensitivity in a simple procedure. It was suggested that false-positive results could occur only if levomepromazine was included in the sample. Other than that, no significant interference that leads to false results was observed in tested common adulterants and additives of supplements. Furthermore, the tube was able to detect tadalafil and analogues in all tested real samples. Accordingly, the proposed test method has the potential for the use of preliminary screening of tadalafil.

Photochlorination-induced degradation of microplastics and interaction with Cr(VI) and amlodipine

Wastewater treatment plants (WWTPs) are the important source of microplastics (MPs) in the environment, and disinfection processes bear high potential to degrade MPs. This study investigated the physicochemical degradation, dissolved organic products and interaction with co-existed pollutants (heavy metal and pharmaceutical) on polyethylene (PE), polypropylene (PP) and polystyrene (PS) MPs during simulated disinfection processes. Compared to photo or chlorination, photochlorination significantly resulted in the physicochemical degradation, including morphology alteration, fragmentation, and chemical oxidation on PP and PS MPs, but showed relatively low effect on PE, indicating the different resistance among polymers to disinfected treatment. Photochlorination also caused the formation of chain-scission organic compounds and even chlorinated products from MPs (e.g. C11H19O4Cl for PP and monochlorophenol, dichlorophenol, chloroacetophenone and chlorobenzoic acid for PS), which may form disinfection byproducts to induce healthy risk. The adsorption potentials of MPs for Cr(VI) or amlodipine were enhanced by photochlorination since the cracking and formed oxygen functional groups enhanced the pore filling and surface precipitation of Cr(VI), and the electrostatic attraction and hydrogen bonding with amlodipine. The findings indicated the physicochemical degradation of MPs and the combined pollution with co-existed pollutants, highlighting the health risks of MP-derived organic products during the disinfection treatments (even in normal dosage) in WWTPs.

Prévalence des Effets Indésirables des Inhibiteurs de Tyrosine Kinase Utilisés dans le Traitement de la Leucémie Myéloïde Chronique au CHU de Sidi Bel-Abbès

Chronic myeloid leukemia (CML) is a malignant hemopathy within the framework of chronic myeloproliferative syndromes, predominant on the granular line. Her drug treatment is based on tyrosine kinase inhibitors (TKIs) which inhibit the abnormal BCR-ABL protein kinase that causes CML and thus block the signals that cause cancer cells to multiply abnormally. However, other proteins are also inhibited, so they can cause a wide range of adverse effects (AEs). The objective of this study was to study the prevalence of AEs of TKIs used in the therapeutic management of CML by the hematology department of University Hospital Center (UHC) of Sidi Bel-Abbes in Algeria and that of the ITK discontinuation following an AE. It was a retrospective descriptive study carried out over a period of four months, from April 01st, 2021 to July 31st, 2021, on CML patients treated with TKI in the hematology department of Sidi Bel-Abbes HUC in Algeria. The primary outcome measure was the prevalence of AEs associated with the use of normal dosages or overdose of the following TKIs: Imatinib, Dasatinib and Nilotinib. Data were collected from patient charts, filled by doctors of hematology department, using questionnaire, and analyzed by Statistical Package for the Social Sciences software, version 20. A total of 40 patients were included, including 22 women, mean age 51.55±11.66years (23-78). Twenty-six patients reported at least one AE. Among the 106 AEs declared, 69 AEs (65.09 %) declared with Imatinib, 26 AEs (24.53 %) with Dasatinib and 11 AEs (10.38 %) with Nilotinib. A predominance of musculoskeletal effects 43 (40.56 %), followed by general disorders 18 (17 %), myelosuppression 14 (13.20 %) and digestive system 12 (11.32 %). AEs were responsible for permanent discontinuation of ITK in three cases (11.54 %), including two cases (07.70 %) on Imatinib because of neutropenia and one case (03.84 %) onDasatinibsuffering from pleural effusion. AEs could be controlled in 13 (50 %) of cases, including 9 (34.62%) by temporary discontinuation and 4 (15.38 %) by reducing the dosage, allowing improvement of symptoms and continuation or reintroduction of treatment. The prevalence of AEs was high in the studied population, their occurrence was inevitable, good management of AEs from the start of treatment is necessary to avoid switching to another TKI, especially in good responders. It is recommended to establish a low-sodium diet beforehand for all TKIs and a low-carbohydrate diet, especially for Nilotinib, and not to rush to stop the TKI because most often, EIs regress over time in order to allow good therapeutic adherence and obtain better results.

"Vaccination in Chronic Kidney Disease: An Overview "

Infection are second leading reason of mortality in individuals with end stages renal diseases, behind cardiovascular disease, and they can cause substantial morbidity in people with chronic kidney disease at an earlier stage. Vaccines are a method of attempting to decrease infection-related morbidity. Although individuals with the CKD or ESRD might not react to immunization and those without renal failures, sufficient seroresponse has been reported with conventional or enhanced influenza, pneumococcus, hepatitis B, or varicella vaccinations. With normal dosage regimens, influenza seems to offer sufficient protection. Despite the fact that some vaccinations are less efficacious in individuals with CKD, there is growing evidence that immunization is beneficial in these groups. Vaccination rates, on the other hand, are low. Given the growing body of data, quality improvement initiatives aimed at improving immunization rate in the patient with all stages of the CKD are required.

Release mechanism between sarcoplasmic protein–bound and free heterocyclic amines and the effects of dietary additives using an in-vitro digestion model

In this study, the release mechanism between free and sarcoplasmic protein–bound heterocyclic amines (HAs) in an in-vitro digestion model were investigated by comparing changes in the amount of HAs between groups with different enzyme dosages and at different digestion stages. The effects of the addition of onions, peppers, and apples on the release mechanism were also studied. We found that bound HAs cannot be completely converted to free HAs under normal enzyme dosages and that a significant increase in HAs occurred in the intestines. The release rate of bound HAs was 5.99%–43.84%, and the total release rate of HAs was 36.67%. Furthermore, the release rate of β-carbolines was the highest (34.41%–43.84%). The addition of onions, peppers, and apples significantly increased the number of free HAs, with growth rates reaching 56.06%, 43.43%, and 54.44%, respectively. These additives mainly promoted the generation of free harman and norharman.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

Management of Psychiatric Disorders in Patients with Hepatic and Gastrointestinal Diseases.

Étude rétrospective sur les effets Indésirables de l’Hydroxychloroquine utilisé dans la prise en charge de la COVID-19 à Sidi Bel-Abbès

Introduction-Objective-According to the French Society of Pharmacology and Therapeutics, severe cardiac adverse reactions have been reported in Covid-19 patients treated with Hydroxychloroquine. The objectives of our study are to evaluate and analyze the adverse reactions related to the Hydroxychloroquine use in Covid-19 treatment in Sidi Bel-Abbès. Material and methods - This is a retrospective descriptive study carried out from March 01st, 2021 to June 30th, 2021 on Covid-19 patients from Sidi Bel-Abbes city, who have developed adverse reactions related to the Hydroxychloroquine use during their treatment using a questionnaire. The primary endpoint was adverse reactions identification associated with normal dosages or overdose use of Hydroxychloroquine. Results -A total of 233 adverse reactions were reported during the study period in 67 patients; 55% were female and 84% were ? 65 years old. The most affected organs were the cardiovascular (28%), the digestive (17%) and the neurological (15%) systems. The severity assessment revealed that the most of them were moderate (50%), followed by severe reactions (39 %) and grave reactions (10 %) without registering a fatal outcome. Conclusion - The study found a predominance of cardiac, digestive and neurological adverse reactions to Hydroxychloroquine. The Monitoring of these effects is necessary for a better management of Covid-19 patients.

Influence of target dose heterogeneity on dose sparing of normal tissue in peripheral lung tumor stereotactic body radiation therapy

ObjectiveTo evaluate the influence of target dose heterogeneity on normal tissue dose sparing for peripheral lung tumor stereotactic body radiation therapy (SBRT).MethodsBased on the volumetric-modulated arc therapy (VMAT) technique, three SBRT plans with homogeneous, moderate heterogeneous, and heterogeneous (HO, MHE, and HE) target doses were compared in 30 peripheral lung tumor patients. The prescription dose was 48 Gy in 4 fractions. Ten rings outside the PTV were created to limit normal tissue dosage and evaluate dose falloff.ResultsWhen MHE and HE plans were compared to HO plans, the conformity index of the PTV was increased by approximately 0.08. The median mean lung dose (MLD), V5, V10, V20 of whole lung, D2%, D1cc, D2cc of the rib, V30 of the rib, D2% and the maximum dose (Dmax) of the skin, and D2% and Dmax of most mediastinal organs at risk (OARs) and spinal cord were reduced by up to 4.51 Gy or 2.8%. Analogously, the median Dmax, D2% and mean dose of rings were reduced by 0.71 to 8.46 Gy; and the median R50% and D2cm were reduced by 2.1 to 2.3 and 7.4% to 8.0%, respectively. Between MHE and HE plans there was little to no difference in OARs dose and dose falloff beyond the target. Furthermore, the dose sparing of rib V30 and the mean dose of rings were negatively correlated with the rib and rings distance from tumor, respectively.ConclusionsFor peripheral lung tumor SBRT, target conformity, normal tissue dose, and dose falloff around the target could be improved by loosening or abandoning homogeneity. While there was negligible further dose benefit for the maximum target dose above 125% of the prescription, dose sparing of normal tissue derived from a heterogeneous target decreased as the distance from the tumor increased.

Genome-wide association studies of toxicity to oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab in 1800 patients with advanced colorectal cancer.

Chemotherapies administered at normal therapeutic dosages can cause significant side-effects and may result in early treatment discontinuation. Inter-individual variation in toxicity highlights the need for biomarkers to personalise treatment. We sought to identify such biomarkers by conducting 40 genome-wide association studies, together with gene and gene set analyses, for any toxicity and 10 individual toxicities in 1800 patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidine chemotherapy ± cetuximab from the MRC COIN and COIN-B trials (385 patients received FOLFOX, 360 FOLFOX + cetuximab, 707 XELOX and 348 XELOX + cetuximab). Single nucleotide polymorphisms (SNPs), genes and gene sets that reached genome-wide or suggestive significance were validated in independent patient groups. We found that MROH5 was significantly associated with neutropenia in MAGMA gene analyses in patients treated with XELOX (P= 6.6 × 10-7 ) and was independently validated in those receiving XELOX + cetuximab; pooled P= 3.7 × 10-7 . rs13260246 at 8q21.13 was significantly associated with vomiting in patients treated with XELOX (odds ratio=5.0, 95% confidence interval=3.0-8.3, P= 9.8 × 10-10 ) but was not independently replicated. SNPs at 139 loci had suggestive associations for toxicities and lead SNPs at five of these were independently validated (rs6030266 with diarrhoea, rs1546161 with hand-foot syndrome, rs9601722 with neutropenia, rs13413764 with lethargy and rs4600090 with nausea; all with pooled P's < 5.0 × 10-6 ). In conclusion, the association of MROH5 with neutropenia and five other putative biomarkers warrant further investigation for their potential clinical utility. Despite our comprehensive genome-wide analyses of large, well-characterised, clinical trials, we found a lack of common variants with modest effect sizes associated with toxicities.

Experimental and modeling research on compression-shear behavior of carbon fiber reinforced coral concrete

With the accelerating development of oceanic resources, the broad application potential of coral concrete (CC) on islands and reefs has been identified. Incorporating carbon fiber (CF) into CC improves its mechanical properties and further expands its application scope. Moreover, many concrete members usually suffer combined compression-shear loading during service. Thus, this work focus on the compression-shear behavior of carbon fiber reinforced coral concrete (CFRCC). Combined compression-shear test results show that the compression-shear failure process can be divided into four stages. The peak shear displacement, peak shear stress, and initial shear stiffness increase are significantly influenced by the normal stress ratio, CF dosage, and concrete strength grade. Secondly, a compression-shear damage model considering the influences of normal stress ratio, CF dosage, and concrete strength is proposed. By comparison, this model is proved to be effective for simulating the shear behavior of CFRCC under combined compression-shear stresses.