Abstract:

Background: Oxidative stress is a key factor in the neurodegenerative disorder. Free radicals may play an important role. Nitric oxide may be implicated in neurotoxicity by a reaction with superoxide, which forms a highly toxic peroxynitrite radical.

Aim: This research aimed to investigate the role of nitric oxide in neuronal damage through Immunohistochemical study.

Material and method: The experiment was divided into 9 groups, each group containing 6 rats selected randomly. Group 1: control normal saline. Group 2: Aβ(1-42). Group 3: L-arginine. Group 4: L-NAME. Group 5: 7-nitroindazole Group 6: donepezil. Group 7: donepezil+ L-arginine. Group 8: donepezil+ L-NAME. Group 9: donepezil+7-nitroindazole. Neurotoxicity was induced by injection of Aβ(1-42) into the rat entorhinal cortex of all animals except the control normal saline group. After the end of the experiment brain was removed quickly for histopathological study.

Results: Aβ(1-42) significantly elevated COX-2 level when compared with control. when compared with Aβ treated rats, L-arginine, L-NAME, 7-nitroindazole and donepezil separately did not improve the changes in COX-2 level. The combination of donepezil with 7-NI is back to normal.

Conclusion: we concluded that NO plays a central role in neurotoxicity and the regulation of NO level is the key to stability and prevention of neurodegenerative disorder.

Keywords: Oxidative stress, Neuroinflammation, Beta amyloid, L- NAME, Donepezil, L-arginine, Nitric oxide, 7-nitroindazole.

Abstract :

Antibody tests can identify people with a resolving or past severe acute respiratory syndrome coronavirus 2 infection and thereby help researchers and public health experts better understand the epidemiology of severe acute respiratory syndrome coronavirus 2. This study is a retrospective study that included 187 Libyan individuals, who attended Attshkhesy (the diagnostic) laboratory in Alkhoms City, Libya, between January 01, 2021, and August 28, 2021. The mean ages of males and females were 48.8 and 46.8, respectively. The study utilized the CLIA quantitative antibody test. To perform the CLIA quantitative antibody test, a high throughput assay apparatus known as the YHLO - iFlash 1800 Chemiluminescence Immunoassay Analyzer was utilized, along with assay reagents called iFlash-SARS-CoV-2 IgM/IgG (manufactured by YHLO Biotech, Shenzhen, China). In female subjects, the concentration of severe acute respiratory syndrome coronavirus 2 IgM was higher than that of IgG in all age groups. Interestingly, in male subjects, the results showed the opposite, where the concentration of severe acute respiratory syndrome coronavirus-2 IgG was much higher than that of IgM in all age groups. When male data were plotted against the female data, the concentration of severe acute respiratory syndrome coronavirus 2 IgM in females was much higher than that of IgM in males in all age groups. Merged IgM-male and IgM-female results showed that IgM concentrations were higher in females than males at all age groups, which means that the incidence of recent COVID-19 infection was higher in females than in males. On the other hand, the IgG antibody prevalence in females was always higher than in males except at age groups 41-50 years and 51-60 years, which can be used as an indicator of high acquired immunity among females due to possible reinfection of females with COVID-19 virus.

Abstract

Objective: The manual counting of gram stained bacteria examined under a microscope becomes difficult when a large number of bacterial cells exist in a microscopic field. The present study was aimed to ease this problem by applying ImageJ software to counting of gram stained bacteria.

Method: This experiment was conducted on Elmergib university, faculty of pharmacy laboratories (Al-Khoms city- Libya). In this study, a microscopic image of a gram stained bacterial cells captured using a student’s smartphone, treated and the bacterial cells were then easily and automatically counted using ImageJ.

Results: According to ImageJ reading, the total number of bacterial particles appeared in the field of a microscopic image were 332 cells.

Conclusion: Direct staining and visualization of organisms for counting can benefit greatly from the use of ImageJ software. This method is less expensive, less contamination and less laborious than other methods and is more rapid and reproducible than counting using manual microscopy methods.

Keywords: ImageJ, Bacterial cells, Automated cell counting

Adrenergic β-blockers are used to treat many conditions, including hypertension, cardiac arrhythmias, heart failure, angina pectoris, migraine, and tremors. The majority of the β-blockers including Propranolol, Metoprolol, Acebutolol, Alprenolol, Betaxolol, Carvedilol, Nebivolol and Oxprenolol are metabolised majorly by CYP2D6, and Bisoprolol is primarily metabolised by CYP3A4 enzymes. The drugs inhibiting or inducing them may alter the pharmacokinetics of those β-blockers. The plasma concentrations of Propranolol might be elevated by the concomitant use of drugs, such as SSRIs (Fluoxetine, Paroxetine), SNRIs (Duloxetine) and Cimetidine, while the plasma concentrations of Metoprolol increased by the concurrent use of SSRIs (Fluoxetine, Paroxetine), Amiodarone, Celecoxib, Cimetidine, Terbinafine, and Diphenhydramine. β-blockers can also interact pharmacodynamically with drugs, including fluoroquinolones, antidiabetic agents and NSAIDs. In addition, β-blockers may interact with herbs, such as curcumin, Ginkgo biloba, Schisandra chinensis, green tea, guggul, hawthorn, St. John’s wort and Yohimbine. This article focuses on clinically relevant drug interactions of β-blockers with commonly prescribed medications. In addition to Pharmacokinetics and Pharmacodynamics of the drug interactions, recommendations for clinical practice are highlighted. The prescribers and the pharmacists are needed to be aware of the drugs interacting with β-blockers to prevent possible adverse drug interactions.

ABSTRACT

BACKGROUND: on the last decade in Libya, the oncology center in Misurata become the most

important cancer diagnosis and follow up center on the western region of Libya. The Libyan

society was worried about the increase of the percentage of tumor incidences among the Libyans

on the last few years. This study focuses on cancer prevalence in city of Misurata and the

surrounding area in central Libya from 2012 to 2016.

METHODS: A hospital-based registry of cancer patients was formed using records from oncology

center in Misurata, focusing on patients who were diagnosed between 2012 and 2016.

RESULTS: the incidence of tumor on females was higher than males from 2014 up to higher

deference on 2016, the most common malignancies in men were cancers of the lung on years from

2012 up to 2015 even though it decrease to 18% of males patients on 2016, followed by colon, its

prevalence rate ranged from 14% to 18% of recorded male patients (For women, they were found

to be cancers of the breast ranged from 29.84% on 2012 and raised to 43.08%. Additionally, agestandardized

rates (ASR) were determined for recording patients who leaved on the city of

Misurata and compared with published record from the other countries. The incidence rates given

for the city of Misurata can be considered with the counties with low malignancy rate

CONCLUSION: Proper surveillance programs need to be in place and healthcare policy should be

adjusted to consider the more prevalent and pressing cancers in society.

Key words : Misurata cancer center, breast cancer, lung cancer, colon cancer, Libya

ABSTRACT

Fat cadherins comprise the largest of all known members of cadherin superfamily. They are present

in all multicellular organisms and retain a high degree of structural conservation. In Drosophila

there are two Fat genes: Fat and Fat-like, whilst in vertebrates there are four members called Fat1,

Fat2, Fat3 and Fat4. Our lab group focused on the use of various biochemical methods to analyse

expression of the FAT1 protein. Because of the high molecular size of FAT1 protein our laboratory

has used affinity purification to prepare bespoke rabbit anti-FAT1 antibodies using FAT1 protein

prepared as GST fusions. five overlapping segments of the FAT1 cytoplasmic tail designated A, B,

C, D and E as GST-fusion proteins contained within pGEX plasmids were assigned in our lab.

According to their sequences and hosted rabbit name antibodies were named N34B, N35B and

N34E. To test the efficacy of each antibody preparation, two different techniques were undertaken,

first Western blotting and second immunofluorescent staining. By this analysis the

immunoreactivity of N34B, N35B and N34E compare favourably with the CTD-pAb. N34E

produced less than satisfactory results in this test with low signal to noise and these results are

omitted here. This staining pattern was largely consistent between N34B and N34E, but the signal

to background was a considerably high. According to that the use of the new B and E antibodies

was restricted to Western blotting where these reagents fulfilled the functional requirements.

Key words: Fat1, Fat1 antibodies, cadherins, western blot. Immunofluorescence staining

Abstract

The loss of cognitive function accompanying healthy aging is not associated with extensive or characteristic patterns of cell death, suggesting it is caused by more subtle changes in synaptic properties. In the hippocampal CA1 region, long-term potentiation requires stronger stimulation for induction in aged rats and mice and long-term depression becomes more prevalent. An age-dependent impairment of postsynaptic calcium homeostasis may underpin these effects. We have examined changes in presynaptic calcium signalling in aged mice using a transgenic mouse line (SyG37) that expresses a genetically encoded calcium sensor in presynaptic terminals. SyG37 mice showed an age-dependent decline in cognitive abilities in behavioural tasks that require hippocampal processing including the Barnes maze, T-maze and object location but not recognition tests. The incidence of LTP was significantly impaired in animals over 18 months of age. These effects of aging were accompanied by a persistent increase in resting presynaptic calcium, an increase in the presynaptic calcium signal following Schaffer collateral fibre stimulation, an increase in postsynaptic fEPSP slope and a reduction in paired-pulse facilitation. These effects were not caused by synapse proliferation and were of presynaptic origin since they were evident in single presynaptic boutons. Aged synapses behaved like younger ones when the extracellular calcium concentration was reduced. Raising extracellular calcium had little effect on aged synapses but altered the properties of young synapses into those of their aged counterparts. These effects can be readily explained by an age-dependent change in the properties or numbers of presynaptic calcium channels.

Neurodegenerative disorders results in inflammatory processes, including inflammatory cytokine secretion and concomitant superoxide production. Acetylcholinesterase inhibitors (AChEIs) influence neuro degeneration through anti-inflammatory effects. Donepezil as an AChEIs also provide neuro protection. This study aimed to evaluate the effect of donepezil (DZ) as a potent acetyl-cholinesterase (AChE) inhibitor, L-NG-Nitroarginine methyl ester (L.NAME) as non-selective nitric oxide synthase inhibitor and 7-nitroindazole (7-NI) as a selective neuronal nitric oxide synthase (NOS) inhibitor against Amyloid beta-peptide (1-42) (Aβ(1-42)) induced neurological disorder. Rats were divided into six groups including control, Aβ(1-42) ,Aβ(1-42) +L-arginine, Aβ(1-42) +L-NAME ,Aβ(1-42) +7-NI, and Aβ(1-42) +DZ. Brain AChE, malondialdehyde, nitric oxide, super oxidedismutase, catalase, reduced glutathione, interleukin 1-beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were measured. Also, brain fatty acids fractions were estimated by high performance liquid chromatography (HPLC). Aβ(1-42) significantly alter levels of brain antioxidant, inflammatory markers and fatty acids content compared to the control group. Treatment with L.NAME, 7-NI and especially DZ improve these parameters. Administration of acetylcholinesterase inhibitors such as DZ attenuates neurodegenerative disorders through decreasing oxidation and inflammation.

Keywords: Neurotoxicity, Aβ (1-42), Donepezil, Nitric oxide, 7-nitroindazole, Fatty acids, HPLC

Genetically encoded calcium indicators (GECIs) have gained widespread use for measurement of neuronal activity but their low expression levels in transgenic mice tend to limit sensitivity. We have developed a transgenic mouse line (SyG37) that expresses a ratiometric calcium sensor, SyGCaMP2-mCherry, that is expressed throughout the brain but targeted to presynaptic terminals. Within the CA1 and CA3 regions of hippocampus of male and female mice, SyGaMP2 fluorescence responds linearly up to 10 electrical stimuli at frequencies up to 100 Hz and it can detect responses to a single stimulus. Responses in single boutons can be measured using multiphoton microscopy. The ensemble amplitude of SyGCaMP2 responses is a function of the number of stimuli applied and the number of contributing boutons. The peak responses and initial rates of calcium influx in single boutons in CA1 and CA3 were similar but the rate of calcium clearance from CA3 boutons after stimulation was significantly faster. In CA1, DNQX reduced SyGCaMP2 responses to Schaffer collateral stimulation to 86% of baseline indicating that 14% of the total response originated from presynaptic terminals of neurones synaptically driven via AMPA receptors. Theta burst stimulation induced long-term potentiation (LTP) of both SyGCaMP2 and fEPSP responses in both young and 18-month-old mice. The proportion of postsynaptically connected terminals increased significantly to 76% of the total after LTP induction. The SyG37 mouse allows stable optical detection of synaptic activation and connectivity at the single bouton level and can be used to characterize the contributions of presynaptic calcium to synaptic transmission and plasticity.

Alzheimer’s disease (AD) is a progressive age-related neurodegenerative disorder characterized by progressive impairment of memory and cognitive functions. Oxidative stress, neuroinflammation, and neurotransmitters disturbance may play an important role. This study aimed to evaluate the effect of donepezil alone and in combination with nitric oxide synthase (NOS) substrate L-arginine, and nitric oxide synthase inhibitor (NOSi) Ng-nitro-l-arginine methyl ester hydrochloride (L-NAME) and 7-nitroindazole against aluminum chloride (AlCl3) induced neurotoxicity. A total of 36 male albino rats were divided to six groups: control normal saline, AlCl3. ,Donepezil, Donepezil+ L-arginine, Donepezil+ L-NAME, and Donepezil+7-nitroindazole. Neurotoxicity was induced by AlCl3 in a dose of 10 mg/Kg subcutaneously for 30 days. After the experimental period, brain was removed for determination of acetylcholinesterase activity (AChE), levels of fatty acids fractions by high performance liquid chromatography (HPLC), interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α). AlCl3 significantly increase brain levels of AChE, IL-1β, and TNF-α, and arachidonic acid (AA) and linoleic acid (LA). Treatment with Donepezil alone and in combination with L.NAME and 7-nitroindazole significantly attenuates these changes. In conclusion, regulation of nitric oxide (NO) level is the key for stability and prevention of neurodegenerative diseases. Combination of Donepezil with nitric oxide synthase inhibitors especially 7-nitroindazole attenuates the oxidant and inflammatory induced by AlCl3.

Keywords: AlCl3, L. NAME, Donpezil, fatty acids, HPLC