Neuroprotective role of vitamin D3 in colchicine-induced Alzheimer’s disease in rats

Background: Alzheimer’s disease (AD) is a complex neurodegenerative disease characterized by progressive decline in memory, language and other cognitive functions. Recent studies provide convincing evidence on the role of vitamin D3 on the nervous system.Aim: To investigate the effect of the active form of vitamin D3 (1,25-dihydroxycholecalciferol) as a neuroprotective agent in experimentally induced AD in rats.Methods: 40 adult male Wistar (albino) rats weighing 180 to 200 g were included in this study. Rats were divided into four groups (each of 10 rats): Group I: normal healthy rats receiving intracerebroventricular injection (icv) of artificial cerebrospinal fluid (ACSF) and serving as a control group. Group II: rats with induced AD by icv colchicine injection of 15 lg/rat bilaterally and receiving no treatment. Group III: rats pre-treated with active form of vitamin D3 42 IU/kg/day subcutaneously (s.c.) for one week followed by induction of AD then post-treated with vitamin D3 in the same dose for 3 weeks. Group IV: rats with induced AD then post-treated with vitamin D3 for 3 weeks. The following parameters were evaluated in rats of all studied groups1- Behavioral assessment: Morris water maze and open field tasks were performed at days   13, 14 and 21 post-icv injection for assessing cognitive, gross behavioral and motor activities of studied groups.2- Biochemical tests: Hippocampal tissue levels of brain derived neurotrophic factor (BDNF), amyloid beta (Ab) peptide, and antioxidant system; glutathione reductase (GR) and glutathione peroxidase (GPX).Results: The present study revealed a significant increase in time latency of water maze test and hippocampal tissue level of Ab peptide concomitant with significant reduction of hippocampal tissue levels of BDNF, GR and GPX, in untreated AD rats (group II) versus control ACSF-injected rats (group I) and vitamin D3-treated AD rats (groups III and IV). However, group III (AD rats pre- and post-treated with vitamin D3) showed a significant decrease in time latency and Ab peptide, and a significant elevation of BDNF, GR and GPX, versus group IV (AD rats post-treated with vitamin D3).Conclusion: Prophylactic use of active form of vitamin D3 (1,25(OH)2D3) appears to possess a neuroprotective effect in AD involving various mechanisms. Hence, vitamin D3 or its analogues can be considered as promising agents for development of new prophylactic and therapeutic neuroprotectors

The role of surfactants in inhibition of uropathogenic E. coli biofilm in catheterized patients in Assiut University Hospitals.

Background: Escherichia coli (E. coli) represent one of the major pathogens implicated in catheter associated urinary tract infection (CAUTI). Formation of biofilm by uropathogenic E. coli (UPEC) is a major survival and persistence mechanism of bacteria against antibiotics and host immune responses in the bladder. This study was designed aiming to evaluate the role of surfactants [non-anionic: Tween 80, anionic: sodium dodecyl sulfate (SDS), cationic: cetyl trimethyl ammonium (CTMA)] on biofilm forming CsgA gene containing strains of E. coli. Methods: A cross sectional study conducted at Assiut University Hospitals ICUs included 100 patients; 53 males and 47 females, catheterized for at least 3 days. Biofilm production by E. coli isolates was detected phenotypically by culture on Congo red agar plates and confirmed genotypically by detection of CsgA by conventional PCR. Overnight broth culture of each E. coli isolate was incubated with each surfactant at 3 different concentrations (CMC). Subculture on congo red agar plates was done. Inhibition of biofilm formation was indicted by fading or absence of black color of the colonies. Results: Tween 80 showed inhibition of biofilm formation by 15% of all samples at a concentration 0.1% (>CMC). SDS show biofilm inhibition by 23% at concentration 2.32mg/ml (=CMC) and at concentration 3mg/ml (>CMC). CTMA inhibited the biofilm formation by 7% at a concentration 0.4mg/ml (=CMC) and by 38% at a concentration 0.8mg/ml (>CMC). Conclusion: Surfactants have disruptive and inhibitory effect on biofilm formation that provides an alternative for plain and medicated catheters

Cleome droserifolia tem atividade anti-esquistossomose mansônica?

The present study was undertaken to assess the effect of the crude extract of Cleome droserifolia (CD) leaves on experimentally infected mice with Schistosoma mansoni. Two groups of mice, showing a patent infection of S. mansoni, one of them was daily treated with an alcoholic extract of CD leaves (0.31 g kg-1 body weight, i.p.) for 21 days. The schistosomicidal activity of the CD extract was evaluated, three weeks post-treatment, on some parasitological and histopathological aspects including worm load, oogram pattern, faecal eggs releasing and granuloma formation. In addition, serum thyroid hormones levels (tri-iodothyronine; T3 and tetra-iodo-thyronin; T4), serum total protein contents and hepatic reduced glutathione (GSH) were evaluated. Treatment using CD extract resulted in a weak reduction in worm burden (32.46%) and affected the viability of both mature and immature eggs as indicated by the increase in the percentage of dead eggs and the decrease in the percentage of live ones. In addition, a week post-treatment, eggs elimination was observed in the stool of the infected-treated group which was low compared to the infected group. There was a suppressive effect of the extract on granuloma formation that could be due to the antioxidant effect of the extract. These data are confirmed by increasing hepatic GSH, serum total proteins and thyroid hormone levels in the infected-treated group as compared to the infected group. Treatment significantly enhanced b globulin fractions of the protein. Based on these assumptions, CD extract has beneficial effects on thyroid hormones status and anti-schistosomiasis activity. The beneficial effects of CD extract could be related to its direct effects on the parasite, and secondary to its effect on the antioxidant capacity of the host. The present study could emphasize the precise mechanism (s) of CD extract protection.O presente estudo foi realizado para verificar o efeito do extrato cru de folhas de Cleome droserifolia (CD) em camundongos experimentalmente infectados com Schistosoma mansoni. Em dois grupos de camundongos mostrando infecção patente por S. mansoni, um deles foi tratado diariamente com extrato alcoólico de folhas de CD (0.31g kg-1 por peso corporal, i.p.) por 21 dias. A atividade esquistossomicida do extrato de CD foi avaliada, três semanas após o tratamento, em alguns aspectos parasitológicos e histopatológicos incluindo carga parasitária, padrão de oograma, eliminação fecal de ovos e formação de granuloma. Além disto, níveis séricos de hormônio tireoideano (tri-iodotironina: T3 e tetra-iodotironina: T4), conteúdo sérico total de proteínas e glutatione hepático reduzido (GSH) foram avaliados. Tratamento usando extrato de CD resultou em fraca redução da carga de vermes (32,46%) e afetou a viabilidade de ovos maduros ou não, como indicado pelo aumento na porcentagem de ovos mortos e o descrécimo na porcentagem de ovos viáveis. Além disso, uma semana após o tratamento, a eliminação de ovos foi observada nas fezes do grupo infectado-tratado que foi baixa comparada ao grupo infectado. Houve efeito supressivo do extrato sobre a formação de granuloma que poderia ser devido ao efeito antioxidante do extrato. Estes dados são confirmados pelo aumento do GSH hepático, soro total de proteínas e níveis dos hormônios tireoideanos no grupo infecto-tratado quando comparado com o grupo infectado. O tratamento aumentou significativamente as frações beta-globulina da proteína. Baseado nestas afirmativas o extrato de CD tem efeitos benéficos sobre o nível dos hormônios tireoideanos e da atividade anti-esquistossomica. Os efeitos benéficos do extrato de CD poderiam estar relacionados com seu efeito direto sobre o parasita, e secundariamente por seus efeitos na capacidade anti-oxidante do hospedeiro. O presente trabalho poderia enfatizar o(s) mecanismo(s) preciso(s) desta proteção do extrato de CD

Uloga kompleksa germanija s L-cysteinom i α-tokoferolom kao stimulatora antioksidativnog obrambenog sustava štakora izloženih gama-zračenju

This study was conducted to evaluate the potency of the newly prepared germanium L-cysteine α-tocopherol complex [germanium dichloro tetrakis (L-cysteinyl-α-tocopherol amide) dichloride] as a protective agent against γ-irradiation-induced free radicals production and liver toxicity. Male Swiss albino rats were injected intraperitoneally with the germanium complex in a concentration of 75 mg kg-1 body mass per dose, for 6 successive doses, last dose administered twenty minutes pre-exposure to a single dose of whole body γ-irradiation of 6.5 Gy. Lipid peroxidation (LPx), nitric oxide (NO), glutathione (GSH) levels, and activity of the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in blood and liver, and blood total protein, cholesterol, triglyceride and α-tocopherol content were estimated as well. The results revealed that administration of germanium complex pre-irradiation resulted in significant (p < 0.001) improvement compared to the irradiated group in the level of hepatic and blood LPx. Hepatic GSH revealed a significant increase (p < 0.001), while its level showed no significant variation in blood. Also, the level of NO in blood and liver increased significantly (p < 0.001). On the other hand, pretreatment with the germanium complex normalized the activities of SOD, GPx and CAT in blood and liver when compared to the irradiated group. The study also documents a marked decrease in the blood triglyceride and cholesterol (p < 0.001); and significant increase (p < 0.001) of -tocopherol and total protein contents in blood. These biochemical changes were associated with marked improvement of histological status. Therefore, the germanium L-cysteine α-tocopherol complex may be a good candidate for ameliorating the changes induced by irradiation, which indicates the beneficial radio-protective role of this antioxidant agent.U radu je procjenjivan kompleks germanija s L-cisteinom i α-tokoferolom [germanijev diklortetrakis (L-cisteinil-α-tokoferol amid) diklorid] kao zaštitno sredstvo protiv slobodnih radikala induciranih γ-zračenjem hepatotoksičnosti. Mužjacima švicarskih albino štakora davan je intraperitonealno kompleks germanija, u 6 sukcesivnih doza po 75 mg kg-1 tjelesne mase, posljednja doza dana je dvadeset minuta prije izlaganja cijelog organizma jednokratnoj dozi γ-ozračivanja od 6,5 Gy. U krvi i jetri praćena je razina lipidne peroksidacije (LPx), dušikovog(II) oksida (NO), glutationa (GSH), aktivnost antioksidativnih enzima glutation peroksidaze (GPx), superoksid dismutaze (SOD) i katalaze (CAT), te količina ukupnih proteina u krvi, kolesterola, triglicerida i α-tokoferola. Rezultati su pokazali da je primjena germanijevog kompleksa značajno (p < 0,001) poboljšala koncentraciju jetrenih i krvnih LPx. Koncentracija GSH u jetri je značajno porasla (p < 0,001), dok se njegova razina u krvi nije značajno promijenila. Koncentracija NO u krvi i jetri značajno se smanjila (p < 0,001). S druge strane, prethodna obrada s kompleksom germanija normalizirala je aktivnost SOD, GPx i CAT u krvi i jetri u odnosu na ozračenu skupinu. Istraživanja su također pokazala značajno smanjenje triglicerida i kolesterola (p < 0,001) i značajno povećanje (p < 0,001) alfa-tokoferola i ukupnih proteina u krvi. Te biokemijske promjene su povezane s izraženim poboljšanjem histoloških promjena u odnosu na ozračenu skupinu. Opisani kompleks germanija mogao bi se kao antioksidativno sredstvo potencijalno upotrijebiti za spriječavanje promjena uzrokovanih zračenjem

SYNTHESIS, ANTITUMOR ACTIVITY, PHARMACOPHORE MODELING AND QSAR STUDIES OF NOVEL PYRAZOLES AND PYRAZOLO [1, 5-A] PYRIMIDINES AGAINST BREAST ADENOCARCINOMA MCF-7 CELL LINE

Objective: The present work aimed to synthesize New series of pyrazoles 3 and pyrazolo[1,5-a]pyrimidines 5, 7, 9 in order to evaluate their antiproliferative activity against human breast adenocarcinoma MCF-7cell line and study the cell cycle progression of the most active compounds. In addition, Pharmacophore modeling and QSAR Studies of these new compounds were done.Methods: The diazonium salt of 4-aminoacetophenone 1 was coupled with malononitrile in ethanol using sodium acetate affords 2-[(4-acetylphenyl)diazenyl] malononitrile Cycloaddition of hydrazine hydrate, in molar ratios 1:1 or 1:2, on compound 2, furnished 3,5-diaminopyrazolederivatives 3a and 3b respectively. Moreover, new pyrazolo[1,5-a]pyrimidine derivatives 5a-f were obtained upon cyclocondensation of 3a, b with different chalcones 4a-c in EtOH/piperidine,while compounds 7a-f were prepared via cycloaddition of 3a, b with various arylidene malononitriles 6a-c in the same reaction condition. Finally, treatment of 3a, b with ethyl 2-cyano-3-ethoxyacrylate 8a or 2-(ethoxymethylene)malononitrile 8b in EtOH/TEA yielded the novel pyrazolo[1,5-a]pyrimidine derivatives 9a, b respectively. These target compounds were screened for their cytotoxic activity against MCF-7 (human breast Cell Line) followed by study cell cycle of 7a. Finally, Pharmacophore modeling and QSAR Studies was carried out.Results: The pyrazolopyrimidine 7a was the most active compound (IC50 = 3.25 µM), whereas, some of the tested compounds exploited moderate growth inhibitory activity. Its effect was further studied on cell cycle progression; results showed that compound 7a induced cell cycle arrest at S-phase verifying this compound as a promising selective anticancer agent.Conclusion: Compound 7a was found to be the most active member against MCF-7 breast cancer (IC50= 3.25 μM), Further biological assessment of 7a using flow-cytometric analysis, revealed that it induced cell cycle arrest at S phase.Keywords: Pyrazole, Pyrazolo[1,5-a]pyrimidine, MCF-7 breast cancer cell line, Cell cycle profile, 3D pharmacophore,1 QSAR stud

Effect of Modifying Mechanical Ventilator Trigger Sensitivity on Arterial Blood Gases in ICU Patients

Background: Despite the fact that mechanical ventilation is an essential part in management of critically ill patients, mechanically ventilated patients have a higher risk of complications, which can lead to increased morbidity and mortality. Objective: This study aimed to study the effect of training inspiratory muscle through modifying mechanical ventilator (MV) trigger sensitivity on arterial blood gases in mechanically ventilated patients. Patients and Methods: Sixty adult patients diagnosed with acute respiratory failure, needed to be intubated and connected to mechanical ventilated. They were from both gender and their ages ranged from 50 to 70 years. The patient were chosen from Intensive Care Unit (ICU), Department of Chest Diseases, Cairo University Hospitals. They were randomly assigned into two equal groups. Group (A): included thirty patients who received training for inspiratory muscle through modifying MV trigger sensitivity plus usual physical therapy. Group (B): included thirty patients who received usual physical therapy only. Results: The results showed a significant increase in partial arterial pressure (PaO2) in both groups, this increasing was significantly higher in&nbsp; patients who received training for the inspiratory muscle plus the usual chest physical therapy than patients who only received usual chest physical therapy (P-value &lt; 0.001). The results showed no significant change in neither power of hydrogen (pH) nor partial pressure of carbon dioxide (PaCO2). Conclusion: Training to inspiratory muscles in mechanically ventilated patient through modifying mechanical ventilator trigger sensitivity can produce a significant increase in partial arterial pressure (PaO2). Although it has no effect in pH nor PaCO2

PROTECTIVE EFFECT OF ONION EXTRACT AGAINST EXPERIMENTAL IMMUNESUPPRESSION IN WISTAR RATS: BIOLOGICAL AND MOLECULAR STUDY

Background: The wrong use of drugs results in disturbances in the immunity that affect human health. These drugs have side effects that may lead to death because of lake of immunity. Human beings need to use natural products to strength the immune system and avoid such side effects. Of these products is the onion that used to strength the immune system. This study was conducted to study the protective effect of onion extract on immune-suppressed rats and its impact on the expression level of cytokines, acute phase proteins and antioxidants compared to both control and immune suppressed groups. Materials and Methods: Forty rats were divided into four groups (10 per group) control group (CNT), immunesuppressed group (DEXA) injected with dexamethasone at a dose of 5 mg per kg intraperitoneally (IP) twice daily for 3 days, onion extract administered group (OE) given orally at a dose of 500 mg per kg for 4 weeks. Group 4 (y), was given onion extract for a week then immune-suppressed with DEXA for 3 days then continued with OE for 3 weeks. Serum and RNA were extracted for examining the biochemical and genetic changes. Results: Injection of dexamethasone decreased number of leukocytes with increase in the number of neutrophils and the decrease of all other types of white blood cells. Moreover, a decrease in antioxidant levels such as catalase, super oxide dismutase (SOD), and reduced glutathione (GSH) with an increase in the level malondialdehyde (MDA). In parallel, a decrease in serum levels of cytokines, such as TNF and IL-6, together with immunoglobulins (IgG and IgM), were reported in DEXA injected rats that were ameliorated by prior administration of OE. Gene expression analysis revealed that dexamethasone suppressed gene expression of antioxidants together with IL-1 and 8 while increased IL- 10 mRNA expression. All of these changes have been normalized to the normal level by OE administration to DEXA injected rats. Conclusion: The present findings clearly emphasize the medical importance of onions as immune-stimulants at genetic and cellular levels, and that they are good for human health

Infraclavicular arterio-arterial prosthetic loop is a safe and effective vascular access technique for haemodialysis in frail patients: a prospective observational study

Vascular access failure causes significant morbidity among end stage renal failure patients. With the increased life expectancy and frailty of those patients, maintaining vascular access became a great challenge. In this study, we assess the short and midterm outcomes of infraclavicular arterio-arterial prosthetic loop (IAAPL) as vascular access for haemodialysis in frail patients who have exhausted conventional vascular access methods. A prospective observational study of 43 patients undergoing IAAPL was conducted in a single centre between May 2017 and March 2020. Primary, assisted primary and secondary patency rates were recorded in addition to complications and patient compliance with access. The achieved primary, assisted primary and secondary patency rates at 6 months are 87.5%, 95%, 97.5% respectively, at one year, corresponding rates were 75%, 83.3%, 94.4% and at 18 months they were 68.6%, 77.1%, 85.7% respectively. There was no procedure related mortality and life-threatening complications during the study period. So we can assume that infraclavicular AAPL is a safe and effective method of obtaining alternative vascular access for hemodialysis in frail patients for whom the conventional vascular access for hemodialysis is not suitable or contraindicated