MYRTUS SPECIES PREVENTS REPRODUCTIVE TOXICITY INDUCED BY DOXORUBICIN IN MALE MICE

Background: Myrtus sp is one of the natural products being used in Unani System of Medicine. Its leaves are frequently used for various ailments like diarrhoea, dysentery, vomiting and osmetic purposes. Objective: the main goal of the present work was to investigate protective effect of Myrtus sp extract against doxorubicin induced sperm abnormalities, genetic toxicity and gene expression alterations. Method: Plant samples were used to obtain plant extraction. Eighty male albino mice were allocated in several groups and treated with doxorubicin alone, doxorubicin plus Myrtus sp extracts for 30 days starting from 24 or 48h after doxorubicin treatment, or supplemented with Myrtus sp extracts for 30 days then treated with doxorubicin treatment. Results: The results revealed that treatment of male mice with doxorubicin then Myrtus sp for one month was the best treatment strategy for protection against doxorubicin induced toxicity. Whereas, Myrtus sp extract significantly preserved male mice from sperm abnormalities induced by doxorubicin treatment, genetic toxicity and gene expression alterations. Conclusion: The results suggested that phenolic compounds exist in the Myrtus sp extract might be contributed to prevention of the reproductive disorders and genotoxicity.Keywords: Myrtus sp, Doxorubicin, Sperm abnormalities, Genetic toxicity, Reproductive gene

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Protective and Therapeutic Effect of Moringa oleifera Leaf Extract on DNA Damage, Cytogenetic Changes, Sperm Abnormalities and High Level of MDA Induced by CCL4 in Rats

ABSTRACT The present study was investigated to evaluate the protective and therapeutic role of Moringa oleifera leaf extract (MOLE) against CCL4-induced toxicity in rats . Male Albino rats of eleven groups (eight animals each) were used in this study : negative control ; control of olive oil ; positive control received CCL4 in olive oil for 12 weeks ; groups 4-7 received CCl4 in olive oil + MOLE at doses 1.3, 2.0, 2.6 and 4.0 gm /kg (used as a protective agent ) for 12weeks . Groups 8-11 received MOLE alone (used as a therapeutic agent ) for 3 weeks after cessation of CCL4 (12 weeks) treatment . DNA damage and level of Melanodialdehyde ( MDA) in liver tissue , as well as cytogenetic changes ( frequency of micronuclei and chromosome aberrations ) in bone marrow cells and sperm abnormalities were analyzed . The calculation of DNA fragmentation using spectrophotometer and analysis of genomic DNA by fractionation on agarose gel were used to assay the DNA damage . The results showed that the CCL4 treatment caused significant induction of genetic aberrations (DNA damage , micronuclei in polychromatic erythrocytes and chromosome aberrations ) and sperm abnormalities as well as significant elevation of MDA level was observed as compared to control . MOLE treatment (as a protective or therapeutic agent ) resulted in significant reduction of genetic aberrations, sperm abnormalities and the level of MDA , in contrast to alterations in all these parameters in rats received CCL4 alone .These results were dose dependent . But better results were obtained by using MOLE as therapeutic agent especially the treatment with the highest dose 4.0 gm / kg., where the percentages of DNA fragmentation , micronuclei , chromosome aberrations and sperm abnormalities and MDA level reverted to near normal . In conclusion , the present investigation is important in presenting data suggesting considerable promise for Moringa oleifera leaf ethanolic extract as a therapeutic agent in CCL4 induced oxidative stress in the rats

Genotoxical, teratological and biochemical effects of anthelmintic drug oxfendazole Maximum Residue Limit (MRL) in male and female mice

Oxfendazole, methyl-5 (6)-phenylsulfinyl-2-benzimidazole carbamate, is a member of the benzimidazole family of anthelmintics. Anthelmintic benzimidazoles are widely used in meat producing animals (cattle, sheep and pigs) for control of endoparasites. The extensive use of veterinary drugs in food-producing animals can cause the presence of small quantities of the drug residues in food. Maximum residue limit or “MRL” means the maximum concentration of residue resulting from the use of a veterinary medicinal product which may be legally permitted recognized as acceptable in food. The FAO/WHO Expert Committee on Food Additives (1999) evaluations of toxicological and residue data, reported that oxfendazole (MRL) has toxicological hazards on human health. The toxicity of oxfendazole (MRL) was tested in male and female mice and their fetuses. Chromosomal aberrations, teratological examination and biochemical analysis were the parameters used in this study. The results show that oxfendazole MRL induced a mutagenic effect in all tested cell types. Also, oxfendazole exhibit embryotoxicity including teratogenicity. The biochemical results show that oxfendazole induced a disturbance in the different biochemical contents of all tested tissues. So, we must increase the attention paid to the potential risk of oxfendazole residues in human beings and should stress the need for careful control to ensure adherence to the prescribed withdrawal time of this drug

A study on mutation points of GDF9 gene and their association with prolificacy in Egyptian small ruminants

Abstract Background Genetic variants of the GDF9 gene were considered to be the potent gene markers for improving fecundity traits in Egyptian sheep and goats. Also, these favorable gene variants could be applied in the breeding program by gene-assisted selection (GAS), aiming towards the potential amelioration of reproduction and production in such small ruminants. The present investigation was designed to evaluate the genetic variants of the GDF9 gene on fecundity traits including the mean number of lambing “MNL” and mean number of twin production “MNTP” of Egyptian sheep and goats. Results This experiment involved 113 mothers, 83 of sheep and 30 of goats, at first, second, third, and fourth parity, and also 26 young females, 12 of sheep and 14 of goats at age of sexual maturation. T-ARMS-PCR analysis was performed on five mutation points (G1, G4, G6, G7, and G8). In sheep, the heterozygous mothers of G4 had significant elevation (P ≤ 0.05) of MNL and MNTP than wild-type homozygous ewes. However, the heterozygous mothers of G1 and G6 gave a reduction of MNL and MNTP as compared to mothers with wild-type genotypes. The ewes of G7 had heterozygous genotype (AG), and the ewes of G8 had wild type (CC). In goat, G4 and G7 were polymorphic, and G1, G6, and G8 were monomorphic type. Based on these findings, it must be selected the young sheep females of heterozygous in G4, and the young goat females of heterozygous in G4 and G7 for participating in a successful breeding program, because they will have potential high fecundity traits. Conclusion The present results confirmed that the genetic variants of the GDF9 gene were considered to be the major gene markers for enhancement of the prolificacy in Egyptian sheep and goats and could be applied in a successful breeding program by gene-assisted selection (GAS) in small ruminants