Peripheral markers of Alzheimer's disease: Surveillance of white blood cells

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. This is a mechanism of innate immunity, which may cause an increase in the number of monocytes and neutrophils circulating in the blood. Literature indicated that chronic inflammation might be a factor in developing neurological problems, including Alzheimer’s, Parkinson’s and other similar illnesses. Our main objective is to identify peripheral markers of Alzheimer’s disease and for that purpose; we are looking at the profile of white blood cells focusing on monocytes, neutrophils, lymphocytes and basophils. Twenty-seven patients of Alzheimer’s disease (AD), diagnosed by magnetic resonance imaging and neuropsychological tests were observed for their blood profile. Key observations during this study were that the levels of monocytes in the blood of the diagnosed AD patients were high irrespective of their age and sex. For those patients whose monocytes were in normal range their neutrophil levels were significantly high. Whereas blood levels of lymphocytes and basophils were found to be constantly low. Escalated levels of monocytes and neutrophils are hallmarks of chronic inflammation and may be precursor to Alzheimer’s disease. A low lymphocyte count specifies that the body’s resistance to fight infection is substantially reduced, whereas low basophil levels indicates their over utilization due to chronic allergic inflammatory condition. Future studies involved closer look at the cytokines produced by these white blood cells especially TNF IL-1, and IL-12, which are products of monocytes. Likewise, blood glucose and creatinine levels were high whereas calcium ions were low. Our studies indicated that white blood cells along with other inflammatory byproducts may act as peripheral markers for early diagnosis of Alzheimer’s disease

The metabolism of serotonin in neuronal cells in culture and platelets and their role in platelet aggregation

The aim of this study is to find a relationship between serotonin (5-HT) and its metabolite 5-hydroxyindol acetic acid (5-HIAA) in hippocampus, frontal neocortex and platelets. Serotonin and 5-HIAA were measured in cultured neurons and compared with those produced by human platelets. The cortical neuronal 5-HIAA/serotonin ratio was 4.7 and for hippocampal neurons it was 3.2. In human platelets, this ratio was 1.35 suggesting that the highest serotonin metabolism occurs in the frontal neocortex followed by the hippocampus and platelets. In the presence of 0.3 M of p-chlorophenylalanine both cultured neurons and platelets exhibited an approximately 50% decrease in serotonin and 5-HIAA concentration suggesting similarities in the metabolic profile in both preparations. In addition, we found that serotonin by itself does not play any role in platelet aggregation but potentates this phenomenon in the presence of calcium ionophore A23187. This synergistic interaction between serotonin (2–5 M) and A23187 (0.5–2 M) was inhibited by serotonin receptor blockers [methysergide (IC50 = 18 M) and cyproheptadine (IC50, 20 M)] and calcium channel blockers (verapamil and diltiazem, IC50 = 20 and 40 M, respectively) that indicate both mechanisms are receptor mediated. Similarly, U73122, an inhibitor of phospholipase C (PLC), blocked the synergistic effect of serotonin and ionophore at an IC50 value of 9.2 M. Wortmannin, a phosphoinositide 3-kinase (PI 3-K) inhibitor, also blocked the response (IC50 = 2.6 M) by inhibiting respiratory burst. However, neither genistein, a tyrosine-speciWc protein kinase inhibitor, nor chelerythrine, a protein kinase C (PKC) inhibitor, affected aggregation. Our results are strongly suggestive of a synergistic interaction between serotonin type-2 and Ca-ionophore via a PLC/Ca signalling pathway

Role of nanostructure molecules in enhancing the bioavailability of oral drugs

Almost all living systems usually based on unique complex nanostructure to control the bimolecular interactions and biochemical reactions that play an important role in metabolism and reproduction. As to understand such relationships, we will be looking at specific nanosystems for focusing the basic structure of different classes of nanostructure molecules, their applications and the role of nanostructure molecules in the enhancement of the bioavailability of drugs. We will be discussing quantum field theory and resultant gluon and kaon involved in the synthesis of cyborg tissue. We are also looking at titanium as a potential candidate for oral medicine of metallic origin. Later on, we will be discussing nanoscience and nanotechnology emphasizingdifferent processes of electronically tunable nanostructures. In the end we will be emphasizing on the usage of metal-based nanomaterials for the bioavailability of the drugs. In this chapter, we will show recent experiments for different compounds, which are promising candidates for antiinflammatory, immunosuppressive, antifertility, anticytogenesis, and anticancer responses

The role of thymoquinone, a major constituent of Nigella sativa, in the treatment of inflammatory and infectious diseases

Nigella sativa (N. sativa) is an annual flowering plant that has been used as a traditional remedy for many centuries. The seed possesses a large variety of compounds with thymoquinone (TQ) considered its major but not sole bioactive constituent. Supercritical fluid extraction, geographical location, and oxidative status of N. sativa produces the highest yield of essential oil content including TQ. Thymoquinone is lipophilic, heat and light sensitive with low oral bioavailability and rapid elimination that have significantly inhibited its pharmacological development. Novel developments in nanoparticulate-based oral administration, nasal spray and transdermal delivery may allow the clinical development of N. sativa and TQ as therapeutic agents. Animal and human studies indicate a potential role of N. sativa seed oil and TQ for a diverse range of disease processes including hypertension, dyslipidaemia, type 2 diabetes mellitus, arthritis, asthma, bacterial and viral infections, neurological and dermatological disorders, as it belongs to the group of pan-assay interference compounds. This review outlines the pharmacological properties of N. sativa and TQ and their potential wide application for a large variety of human diseases. The paper will focus on recent studies of the anti-inflammatory and antiviral properties that make N. sativa and TQ promising therapeutic agents targeting contemporary inflammatory and infectious diseases including Covid 19

Heart Rate Variability Time Analyses of the Streptozotocin- Diabetic Rat

As the world prevalence of diabetes mellitus (DM) increases, animal models of the disease's progression are required for researching effective treatment. The streptozotocin (STZ) treated rat is known to cause hyperglycaemia. This study confirms that this animal model also displays DM physiological effects in the animal heart rate (HR) and heart rate variability (HRV). In particular, 5 minutes of rat (n=13) electrocardiogram (ECG) is acquired hourly for 30 days. At day 10, the animal (n=7) is dosed with STZ and the ECG is analyzed in order to determine the HR and HRV. The HRV is indexed using two time-based analyses, based on long-term (24hr) and short-term (5min) analyses. All analyses are compared to control non-STZ dosed animals (n=6) and display significant DM effects