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1.
Vaccines (Basel) ; 9(3)2021 Mar 03.
Article in English | MEDLINE | ID: mdl-33802467

ABSTRACT

Since the emergence of SARS-CoV-2 at the end of 2019, 64 candidate vaccines are in clinical development and 173 are in the pre-clinical phase. Five types of vaccines are currently approved for emergency use in many countries (Inactivated, Sinopharm; Viral-vector, Astrazeneca, and Gamaleya Research Institute; mRNA, Moderna, and BioNTech/Pfizer). The main challenge in this pandemic was the availability to produce an effective vaccine to be distributed to the world's population in a short time. Herein, we developed a whole virus NRC-VACC-01 inactivated candidate SARS-CoV-2 vaccine and tested its safety and immunogenicity in laboratory animals. In the preclinical studies, we used four experimental animals (mice, rats, guinea pigs, and hamsters). Antibodies were detected as of week three post vaccination and continued up to week ten in the four experimental models. Safety evaluation of NRC-VACC-01 inactivated candidate vaccine in rats revealed that the vaccine was highly tolerable. By studying the effect of booster dose in the immunological profile of vaccinated mice, we observed an increase in neutralizing antibody titers after the booster shot, thus a booster dose was highly recommended after week three or four. Challenge infection of hamsters showed that the vaccinated group had lower morbidity and shedding than the control group. A phase I clinical trial will be performed to assess safety in human subjects.

2.
Blood Coagul Fibrinolysis ; 19(1): 7-13, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18180609

ABSTRACT

Changes in plasma tissue factor (TF)-activated factor VII (FVIIa) and plasma tissue factor pathway inhibitor (TFPI) in type II diabetes mellitus are assessed, vascular complicated and noncomplicated patients compared, and whether these novel hemostatic activity markers predict vascular complications in diabetic patients, improving risk assessment, is determined. Fifty type II diabetic patients and 20 healthy controls (age, sex and body mass matched) underwent medical history and examination, fasting plasma glucose level, glycosylated hemoglobin (HbA1c), lipid profile, hemostatic parameters, plasma TF activity, and TFPI and TF expression on blood monocytes. Mean TF, TF activity, TFPI, and FVIIa significantly increased among hyperlipidemic compared with normolipidemic diabetic patients, and normolipidemic diabetic patients compared with controls. Mean percentage TF-positive monocytes with and without lipopolysaccharide, plasma TF activity, TFPI and FVIIa were significantly higher among complicated than noncomplicated diabetic patients. Mean percentage TF-positive monocytes without and with lipopolysaccharide, plasma TF activity, plasma TFPI and FVIIa were higher among diabetic patients with macrovascular compared with microvascular complications. High significant correlation occurred between HbA1c, triglycerides and percentage TF-positive monocytes with and without lipopolysaccharide stimulation, plasma TF activity and both FVIIa and TFPI. High activity levels of plasma TF and FVIIa with increased circulating TF-positive monocytes occurred in type II diabetic patients, especially with vascular complications. Results reflect high procoagulant activity possibly involved in diabetic vascular complications. Elevated TFPI levels were observed, but were not sufficient to balance high procoagulant activity. Correlation of procoagulant activity markers with HbA1c reinforces the importance of optimal glycemic control in type II diabetes.


Subject(s)
Diabetes Mellitus, Type 2/blood , Factor VIIa/metabolism , Lipoproteins/metabolism , Monocytes/physiology , Thromboplastin/metabolism , Adult , Aged , Case-Control Studies , Diabetes Complications/blood , Female , Glycated Hemoglobin , Humans , Hyperlipidemias/complications , Male , Middle Aged
3.
Lab Med ; 48(3): 225-229, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28460053

ABSTRACT

BACKGROUND: Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes mellitus. Until now, patients in developing countries who had this condition had been misdiagnosed as having type 1 diabetes mellitus and accordingly directed to erroneous, ineffective, and costly therapeutic regimens. OBJECTIVE: To detect Egyptian patients who harbor pathological variant in the KCNJ11 gene, so that their treatment regimen can be modified as needed to increase its effectiveness. METHODS: We sequenced KCNJ11 in 17 ethnic Egyptian probands diagnosed with diabetes mellitus before age 2 years. RESULTS: A preliminary case individual harboring a KCNJ11 pathological variant (p.R201H) was identified. The patient was successfully shifted from insulin therapy to sulfonylurea. Four previously identified benign variants, namely, E23K, I337V, L270V, and A190A, were detected in this patient. CONCLUSION: Implementing the findings of this molecular analysis could have a major clinical and nationwide economic impact on world health, especially in developing countries.


Subject(s)
DNA Mutational Analysis , Diabetes Mellitus , Potassium Channels, Inwardly Rectifying/genetics , Adolescent , Child , Child, Preschool , Cross-Sectional Studies , Diabetes Mellitus/diagnosis , Diabetes Mellitus/drug therapy , Diabetes Mellitus/genetics , Diabetes Mellitus, Type 1 , Diagnostic Errors , Egypt , Female , Humans , Infant , Male , Mutation , Prospective Studies , Sulfonylurea Compounds/therapeutic use
4.
Saudi J Ophthalmol ; 24(4): 125-32, 2010 Oct.
Article in English | MEDLINE | ID: mdl-23960889

ABSTRACT

PURPOSE: To determine the effects of retinal vein occlusion (RVO) on multifocal electroretinogram (MF-ERG) parameters, to correlate MF-ERG and standard electroretinogram (ERG) and to correlate MF-ERG with findings of optical coherence tomography (OCT) in cases of RVO. METHODS: Both eyes of 50 patients with RVO and 50 eyes of 25 normal subjects were examined using MF-ERG, standard ERG, fluorescein angiography and OCT. The latency in millisecond (ms) and response density in nanovolt (nv/degenerations) were measured for each of four quadrant areas and central area. OCT was used to measure the foveal retinal thickness. Fluorescein angiography was used to measure retinal ischemia. RESULTS: Central retinal vein occlusion (CRVO) markedly affected all parameters of MF-ERG. In pathological quadrants in branch retinal vein occlusion, the response densities of MF-ERG were decreased and latencies of p-wave were prolonged. The MF-ERG responses obtained from eyes with RVO were significantly different (P > 0.05) from derived from the fellow eyes. The amplitude of MF-ERG were abnormal in 40 eyes and implicit times were delayed in 48 eyes compared with normal subjects. While 30 Hz flicker implicit were abnormal in only 24 eyes with RVO. Implicit times were prolonged in eyes with macular ischemia than in eyes without ischemia. There were significant correlation between foveal retinal thickness measured by OCT and P response density MF-ERG in cases of retinal vein occlusion. CONCLUSION: MF-ERG is more susceptible than standard ERG to eye changes of RVO due to the multiple frequencies of stimulation used to record MF-ERG response. MF-ERG could be sensitive indicator of underlying disease affecting the retinal in eyes with RVO. MF-ERG is useful for detecting local retinal dysfunction in patients with RVO and sensitive to morphological changes and functional disorders induced by RVO.

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