N-acetylcysteine versus progesterone on the cisplatin-induced peripheral neurotoxicity

Background: Cisplatin-induced peripheral nerve neurotoxicity (CIPN) is the main obstacle in cisplatin treatment. The aim of this study was to compare the modulatory effects of N-acetylcysteine (NAC) and progesterone on CIPN, because there are scarce literature data on the protective effect of the proge­sterone on the CIPN. Materials and methods: Twenty-four rats were divided into four groups: control, cisplatin-treated, concomitant cisplatin-treated and NAC-treated, and concomitant cisplatin-treated and progesterone-treated. Electron microscopic, immunohistochemical, real time polymerase chain reaction and histomorphome­tric analysis; oxidative/antioxidative markers (MDA/GSH and SOD), neurotoxic/ neuroprotective markers (iNOS/nNOS), inflammatory mediators (TNF-a and NF-kB) and BAX were done. Results: The myelin sheath in the cisplatin-treated group elucidated infolding. The myelin was disfigured, degenerated, and extensively split with areas of focal loss. The axoplasm was atrophic. Ballooning and vacuolations of the mitochon­dria with alterations of Remak bundles structures were observed. Fewer of these changes were noted in the NAC and progesterone-treated groups. Decrease of the antioxidant SOD and GSH (81% and 64%) and increase of the oxidant MDA (9 folds), increment of the neurotoxic iNOS (1.9 folds) and decrement of the neuroprotective nNOS (64%) and elevation of the inflammatory mediators’ TNF-a and NF-kB (8.3 and 11 folds) in the cisplatin-treated group. Increase of the antioxidant SOD (1.3 and 2.5 folds) and GSH (120% and 79%) and decrease of the oxidant MDA (69% and 88%), decrement of the neurotoxic iNOS (56% and 68%) and increment of the neuroprotective nNOS (1.6 and one folds) and elevation of the inflammatory mediators’ TNF-a and NF-kB were observed in the NAC and progesterone-treated groups, respectively. Conclusions: The toxic effect of CIPN might be attributed to either oxidative or severe inflammatory stress. Progesterone is efficient in ameliorating these effects; however, NAC is better. (Folia Morphol 2018; 77, 2: 234–245

Sinteza i antimikrobno djelovanje fuzioniranih heterocikličkih pirola

Pyrrole derivatives 1a,b were used as precursors for the preparation of pyrrolo[2,3-d]pyrimidine derivatives 2a,b-7a,b. Also, the formation and structure of different pyrrolotriazolopyrimidine derivatives 8a,b-11a,b were discussed. Some of the prepared products showed potent antimicrobial activity.Pirolni derivati 1a,b upotrebljeni su kao prekursori za pripravu derivata pirolo2,3-dpirimidina 2a,b7a,b. Diskutirano je i nastajanje i struktura različitih derivata pirolotriazolopirimidina 8a,b11a,b. Neki od sintetiziranih spojeva posjeduju izraženo antimikrobno djelovanje

Molecular diagnosis in recessive pediatric neurogenetic disease can help reduce disease recurrence in families.

BackgroundThe causes for thousands of individually rare recessive diseases have been discovered since the adoption of next generation sequencing (NGS). Following the molecular diagnosis in older children in a family, parents could use this information to opt for fetal genotyping in subsequent pregnancies, which could inform decisions about elective termination of pregnancy. The use of NGS diagnostic sequencing in families has not been demonstrated to yield benefit in subsequent pregnancies to reduce recurrence. Here we evaluated whether genetic diagnosis in older children in families supports reduction in recurrence of recessive neurogenetic disease.MethodsRetrospective study involving families with a child with a recessive pediatric brain disease (rPBD) that underwent NGS-based molecular diagnosis. Prenatal molecular testing was offered to couples in which a molecular diagnosis was made, to help couples seeking to prevent recurrence. With this information, families made decisions about elective termination. Pregnancies that were carried to term were assessed for the health of child and mother, and compared with historic recurrence risk of recessive disease.ResultsBetween 2010 and 2016, 1172 families presented with a child a likely rPBD, 526 families received a molecular diagnosis, 91 families returned to the clinic with 101 subsequent pregnancies, and 84 opted for fetal genotyping. Sixty tested negative for recurrence for the biallelic mutation in the fetus, and all, except for one spontaneous abortion, carried to term, and were unaffected at follow-up. Of 24 that genotyped positive for the biallelic mutation, 16 were electively terminated, and 8 were carried to term and showed features of disease similar to that of the older affected sibling(s). Among the 101 pregnancies, disease recurrence in living offspring deviated from the expected 25% to the observed 12% ([95% CI 0·04 to 0·20], p = 0·011).ConclusionsMolecular diagnosis in an older child, coupled with prenatal fetal genotyping in subsequent pregnancies and genetic counselling, allows families to make informed decisions to reduce recessive neurogenetic disease recurrence

Novel Sequence Variants in the NPC1 Gene in Egyptian Patients with Niemann-Pick Type C

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare, autosomal recessive, progressive neuro-visceraldisease caused by biallelic mutations in either NPC1gene (95% of cases) or NPC2 gene. AIM: This caseseries study aimed at the molecular analysis of certain hot spots of NPC1 genein NPC Egyptian patients. METHODS: The study included 15 unrelated NPC patients and selected parents,as well as20 healthy controls of matched sex and age. Clinical investigations were performed according to well established clinical criteria. Assessment of the chitotriosidase level, as an initial screening tool for NPC, was done in all cases. Polymerase chain reaction amplification of NPC1 exons (17–25) encountering the hotspot residues (855–1098 and1038–1253) was carried out followed by direct sequencingfor mutational analysis. RESULTS: All includedpatients with mainly neurovisceral involvement were characterized. The onset of the disease varied from early-infantile (58.3%) to late-infantile (26.7%) and juvenile-onset (6.7%). Ahigh chitotriosidase level wasobservedin all patients. Molecular analysis of NPC1 (exons 17–25) confirmed 15 mutant alleles out of 30 studied ones. They included two novel homozygous missense variants (p.Ser1169Arg and p.Ser1197Phe) and previously reportedfour mutations (p.Arg958*, p.Gly910Ser, p.Ala927Glyfs*38, and andp.Cys1011*). CONCLUSION: The two studied amino acid residues (855–1098 and 1038–1253) could beconsidered aspotential hotspot regions in NPC1 Egyptian patients

DISSIPATION OF MALATHION IN DILL AND CORIANDER PLANTS AND THEIR OILS

The insecticide malathion (57% E.C.) was applied at the rate of 712.5 gm active ingredient per feddan on dill, Anethum graveolens L. and coriander, Corianderum sativum L. for controlling aphids infesting these plants. An analytical method, using gas chromatography equipped with flame photometric detector was used for detecting the insecticide residues. A field trial was conducted to determine the rate of dissipation of malathion in dill and coriander plants and in the resulting oil. Residue analysis showed that the initial deposits determined one hour after application were 35.81 & 22.7 ppm in dill and coriander plants, respectively. Rates of dissipation of malathion were 4.72, 51.1, 68.39, 88.41 and 93.49% in dill plants and were 13.61, 43.22, 66.78, 86.26 and 91.85% in coriander plants at 1, 3, 7, 14 and 21 days post treatment, respectively. The pesticide was decayed quite rapidly in and on dill and coriander plants and detectable residues (1.62 and 0.93 ppm) were observed in these plants 28 days after treatment. At harvest 46 days for coriander and 70 days for dill after application malathion was found at average levels of 0.78 mg/kg and 0.54 mg/kg in dill and coriander dry seed, respectively. The volatile oil extracted from the seed by steam distillation process was contaminated with the insecticide at a higher levels than in the seed [about sevenfold in dill oil, 5.21 mg/kg and ninteenfold in coriander oil 10.16 mg/kg]. This means that malathion had tendency to co-distill with the dill and coriander oil throughout steam distillation process

In vitro antiproliferative and antioxidant activities of the extracts of Muntingia calabura leaves.

The in vitro antiproliferative and antioxidant activities of the aqueous, chloroform and methanol extracts of Muntingia calabura leaves were determined in the present study. Assessed using the 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay, the aqueous and methanol extracts of M. calabura inhibited the proliferation of MCF-7, HeLa, HT-29, HL-60 and K-562 cancer cells while the chloroform extract only inhibited the proliferation of MCF-7, HeLa, HL-60 and K-562 cancer cells. Interestingly, all extracts of M. calabura, which failed to inhibit the MDA-MB-231 cells proliferation, did not inhibit the proliferation of 3T3 (normal) cells, indicating its safety. All extracts (20, 100 and 500 μg/ml) were found to possess antioxidant activity when tested using the DPPH radical scavenging and superoxide scavenging assays with the methanol, followed by the aqueous and chloroform, extract exhibiting the highest antioxidant activity in both assays. The total phenolic content for the aqueous, methanol and chloroform extracts were 2970.4 ± 6.6, 1279.9 ± 6.1 and 2978.1 ± 4.3 mg/100 g gallic acid, respectively. In conclusion, the M. calabura leaves possess potential antiproliferative and antioxidant activities that could be attributed to its high content of phenolic compounds, and thus, needs to be further explored

¹H-NMR metabolic profiling, antioxidant activity, and docking study of common medicinal plant-derived honey

The purpose of this investigation was to determine ¹H-NMR profiling and antioxidant activity of the most common types of honey, namely, citrus honey (HC1) (Morcott tangerine L. and Jaffa orange L.), marjoram honey (HM1) (Origanum majorana L.), and clover honey (HT1) (Trifolium alexandrinum L.), compared to their secondary metabolites (HC2, HM2, HT2, respectively). By using a ¹H-NMR-based metabolomic technique, PCA, and PLS-DA multivariate analysis, we found that HC2, HM2, HC1, and HM1 were clustered together. However, HT1 and HT2 were quite far from these and each other. This indicated that HC1, HM1, HC2, and HM2 have similar chemical compositions, while HT1 and HT2 were unique in their chemical profiles. Antioxidation potentials were determined colorimetrically for scavenging activities against DPPH, ABTS, ORAC, 5-LOX, and metal chelating activity in all honey extract samples and their secondary metabolites. Our results revealed that HC2 and HM2 possessed more antioxidant activities than HT2 in vitro. HC2 demonstrated the highest antioxidant effect in all assays, followed by HM2 (DPPH assay: IC50 2.91, 10.7 μg/mL; ABTS assay: 431.2, 210.24 at 50 ug/mL Trolox equivalent; ORAC assay: 259.5, 234.8 at 50 ug/mL Trolox equivalent; 5-LOX screening assay/IC50: 2.293, 6.136 ug/mL; and metal chelating activity at 50 ug/mL: 73.34526%, 63.75881% inhibition). We suggest that the presence of some secondary metabolites in HC and HM, such as hesperetin, linalool, and caffeic acid, increased the antioxidant activity in citrus and marjoram compared to clover honey

Evaluation of the Native Killer Yeasts against the Postharvest Phytopathogenic mould of Balady Orange Fruits

Yeasts are some of the most important postharvest biocontrol agents (BCAs). Postharvest oranges frequently deteriorate due to green and blue moulds, leading to significant economic losses. The purposes of the present study were to isolate blue and green moulds from infected orange fruits, to assess the ability of killer yeasts isolated from healthy orange fruits and leaves from orange orchards to control blue and green moulds and to evaluate the additive effect of BCAs in combination with 2% sodium bicarbonate (SBC), 2%, sodium benzoate (SB), 2% calcium chloride, 0.2% salicylic acid (SA) or 0.5% chitosan. Among eight fungi isolated from orange fruits showing symptoms of green and blue mulds infection, two were identified as P. digitatum and P. italicum and selected for in vitro assays. Twenty eight yeast isolates were obtained from orange leaves and from the surface of fruits. All yeasts exhibited high killer activity. Twelve yeasts reduced 22.5 –70% of P. digitatum growth while seven isolates reduced 21.1- 68.5% of P. italicum growth. The most potent yeast isolates were identified as Candida pseudotropicalis, Candida salmanticensis, Candida membranifaciens and Pichia guilliermondii. Combination of the BCAs, C. pseudotropicalis, C. salmanticensis and P. guilliermondii with SBC, CaCl2 or chitosan increased their effectiveness against P. digitatum. While combination of C. pseudotropicalis, C. membranifaciens and P. guilliermondii with these natural compounds decreased their effectiveness against P. italicum. Combination of C. membranifaciens with SA increased its effectiveness against P. digitatum. Sodium benzoate has additive effect on C. pseudotropicalis against P. digitatum and C. pseudotropicalis and P. guilliermondii against P. italicum

Correction: Guidelines for the prevention, detection and management of the renal complications of COVID-19 in Africa

The authors of the article ‘Guidelines for the prevention, detection and management of the renal complications of COVID-19 in Africa’ [1] wish to acknowledge the contribution of Professor Hussein El Fishawy. Our guidelines drew on various sources, including the Egyptian Ministry of Health guidelines, portions of which were adapted and reproduced with permission from the Egyptian Ministry of Health. Two of the authors of those guidelines, Professors Elsayed and Zaki, are also coauthors of our paper. Professor El Fishawy was the third author of the Egyptian guidelines and we would like to acknowledge his contribution to our review through this source, especially with respect to the treatment algorithms for patients with kidney transplants and those with acute kidney injury. Reference1. Elsayed HM, Wadee S, Zaki MS, Were AJO, Ashuntantang GE, Bamgboye EL, et al. Guidelines for the prevention, detection and management of the renal complications of COVID-19 in Africa. Afr J Nephrol. 2020; 23(1):109-126