Pharmacological

The nociceptor TRPA1 is thought to be activated through covalent modification of specific cysteine residues on the N terminal of the channel. The precise mechanism of covalent modification with unsaturated carbonyl-containing compounds is unclear, therefore by examining a range of compounds which can undergo both conjugate and/or direct addition reactions we sought to further elucidate the mechanism(s) whereby TRPA1 can be activated by covalent modification. Calcium signalling was used to determine the mechanism of activation of TRPA1 expressed in HEK293 cells with a series of related compounds which were capable of either direct and/or conjugate addition processes. These results were confirmed using physiological recordings with isolated vagus nerve preparations. We found negligible channel activation with chemicals which could only react with cysteine residues via conjugate addition such as acrylamide, acrylic acid, and cinnamic acid. Compounds able to react via either conjugate or direct addition, such as acrolein, methyl vinyl ketone, mesityl oxide, acrylic acid NHS ester, cinnamaldehyde and cinnamic acid NHS ester, activated TRPA1 in a concentration dependent manner as did compounds only capable of direct addition, namely propionic acid NHS ester and hydrocinnamic acid NHS ester. These compounds failed to activate TRPV1 expressed in HEK293 cells or mock transfected HEK293 cells. For molecules capable of direct or conjugate additions, the results suggest for the first time that TRPA1 may be activated preferentially by direct addition of the thiol group of TRPA1 cysteines to the agonist carbonyl carbon of α,β-unsaturated carbonyl-containing compounds.

Jojoba [Simmondsia chinensis (Link 1822) Schneider 1907] is an arid perennial shrub grown in several American and African countries. Jojoba seeds, which are rich in liquid wax, were used in folk medicine for diverse ailments. In the current study, the potential anti-inflammatory activity of jojoba liquid wax (JLW) was evaluated in a number of experimental models. Results showed that JLW caused reduction of carrageenin-induced rat paw oedema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In a test for anti-inflammatory potential utilizing the chick’s embryo chroioallantoic membrane (CAM), JLW also caused significant lowering of granulation tissue formation. Topical application of JLW reduced ear oedema induced by croton oil in rats. In the same animal model, JLW also reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In addition, JLW ameliorated histopathological changes affected by croton oil application. In the lipopolysaccharide (LPS)-induced inflammation in air pouch in rats, JLW reduced nitric oxide (NO) level and tumor necrosis factor-α (TNF-α) release. In conclusion, this study demonstrates the effectiveness of JLW in combating inflammation in several experimental models. Further investigations are needed to identify the active constituents responsible for the anti-inflammatory property of JLW.

Cellular protection against the deleterious effects of reactive oxidants generated in aerobic metabolism, called oxidative stress, is organized at multiple levels. Defense strategies include three levels of protection; prevention, interception, and repair. Regulation of the ...

This paper is the third part of a survey about patient information and the use of patient package leaflet. The aim of this research section is to analyse the role of the pharmacy and the pharmacist in the health-care field. By means of answers of interviewed people, informations were obtained about the purchase of drugs and other products in pharmacy, the consumer requirements, the non-medical products and self-medication channels of information, the patient-physician and patient-pharmacist quality of communication and the role of advertising for drugs and other products sold in pharmacy. From this survey, it emerged that most of the respondents go to pharmacy to purchase drugs exclusively and only a small number of people go to purchase other products. The pharmacist does not play a remarkable role in providing health information to the patient.

We describe here the main natural compounds used in cancer therapy and prevention, the historical aspects of their application and pharmacognosy. Two major applications of these compounds are described: as cancer therapeutics and as chemopreventive compounds. Both natural compounds, extracted from plants or animals or produced by microbes (antibiotics), and synthetic compounds, derived from natural prototype structures, are being used. We also focus on the molecular aspects of interactions with their recognized cellular targets, from DNA to microtubules. Some critical aspects of current cancer chemotherapy are also discussed, focusing on genetics and genomics, and the recent revolutionary theory of cancer: aneuploidy as the primum movens of cancer.

In this review we would like to aim at pharmaceuticals engineered on the nanoscale, i.e. pharmaceuticals where the nanomaterial plays the pivotal therapeutic role or adds additional functionality to the previous compound. Those cases would be considered as nanopharmaceuticals. The development of inorganic systems is opening the pharmaceutical nanotechnology novel horizons for diagnosis, imaging and therapy mainly because of their nanometer-size and their high surface area to volume ratios which allow for specific functions that are not possible in the micrometer-size particles. This review will focus on pharmaceutical forms that are based on inorganic nanoparticles where the nanosize of the inorganic component provides unique characteristics to the pharmaceutical form. Several examples of these systems that are either in pre-clinical investigation and under examination by the Food and Drug Administration (FDA) or that have been already approved by the FDA and are in clinical practice today like Gastromark®, NanoTherm®, Colloidal Gold for Lateral Flow tests, HfO-NPs, BioVant™ will be described and reviewed.

The present work offers a review addressing the chemistry and pharmacology of Limnophila aromatica (Lamk.) Merr. (Belonging to Scrophulariaceae family) regarded as one of the most significant plant species in traditional system of medicine and is established as a source of flavonoids, terpenoids etc. The isolated phytochemicals as well as different extracts exhibited significant biological activities such as antimicrobial, antioxidant, vascular protective activities. Exhaustive research regarding isolation of more phytochemicals and pharmacology study on this medicinal plant is still necessary so as to explore the plant regarding its medicinal importance. Therefore, the aim of this review is to boost up present day researchers in this direction to undertake further investigation of this plant for searching new drugs. The present review covers literature up to January 2014 and enlists 24 references.

The microbiota of Westerners is significantly reduced in comparison to rural individuals living a similar lifestyle to our Paleolithic forefathers but also to that of other free-living primates such as the chimpanzee. The great majority of ingredients in the industrially produced foods consumed in the West are absorbed in the upper part of small intestine and thus of limited benefit to the microbiota. Lack of proper nutrition for microbiota is a major factor under-pinning dysfunctional microbiota, dysbiosis, chronically elevated inflammation, and the production and leakage of endotoxins through the various tissue barriers. Furthermore, the over-comsumption of insulinogenic foods and proteotoxins, such as advanced glycation and lipoxidation molecules, gluten and zein, and a reduced intake of fruit and vegetables, are key factors behind the commonly observed elevated inflammation and the endemic of obesity and chronic diseases, factors which are also likely to be detrimental to microbiota. As a consequence of this lifestyle and the associated eating habits, most barriers, including the gut, the airways, the skin, the oral cavity, the vagina, the placenta, the blood–brain barrier, etc., are increasingly permeable. Attempts to recondition these barriers through the use of so called ‘probiotics’, normally applied to the gut, are rarely successful, and sometimes fail, as they are usually applied as adjunctive treatments, e.g. in parallel with heavy pharmaceutical treatment, not rarely consisting in antibiotics and chemotherapy.It is increasingly observed that the majority of pharmaceutical drugs, even those believed to have minimal adverse effects, such as proton pump inhibitors and anti-hypertensives, in fact adversely affect immune development and functions and are most likely also deleterious to microbiota. Equally, it appears that probiotic treatment is not compatible with pharmacological treatments. Eco-biological treatments, with plant-derived substances, or phytochemicals, e.g. curcumin and resveratrol, and pre-, pro- and syn-biotics offers similar effects as use of biologicals, although milder but also free from adverse effects. Such treatments should be tried as alternative therapies; mainly, to begin with, for disease prevention but also in early cases of chronic diseases. Pharmaceutical treatment has, thus far, failed to inhibit the tsunami of endemic diseases spreading around the world, and no new tools are in sight. Dramatic alterations, in direction of a paleolithic-like lifestyle and food habits, seem to be the only alternatives with the potential to control the present escalating crisis. The present review focuses on human studies, especially those of clinical relevance.

Various lines of evidence indicate the presence of progressive pathophysiological processes occurring within the brains of patients with schizophrenia. By modulating chemical neurotransmission, antipsychotic drugs may influence a variety of functions regulating neuronal resilience and viability and have the potential for neuroprotection. This article reviews the current literature describing preclinical and clinical studies that evaluate the efficacy of antipsychotic drugs, their mechanism of action and the potential of first- and second-generation antipsychotic drugs to exert effects on cellular processes that may be neuroprotective in schizophrenia. The evidence to date suggests that although all antipsychotic drugs have the ability to reduce psychotic symptoms via D(2) receptor antagonism, some antipsychotics may differ in other pharmacological properties and their capacities to mitigate and possibly reverse cellular processes that may underlie the pathophysiology of schizophrenia.

Severe acute respiratory syndrome 2 (SARS-CoV-2) is a novel coronavirus that causes coronavirus disease 2019 (COVID-19), an infection characterized by flu-like symptoms, progressing in some cases to acute respiratory distress syndrome (ARDS). That WHO to declare it as global pandemic. Based on the information gained from the responses to other RNA coronaviruses, including the strains that cause severe acute respiratory syndrome (SARS)-coronaviruses and Middle East respiratory syndrome (MERS), effort are put in place to develop effective therapeutic agent against the COVID-19. Currently, there is no therapeutic candidate for this virus but the United States Food and Drug Administration (FDA) has provided emergency authorization for the use of chloroquine and hydroxychloroquine and other promising antiviral drugs. Although the result of ongoing clinical trials are not out, but some provide promising result in vitro. The most important factor associated with pathophysiology of SARS-CoV-2 is the host immune response which results due to binding of spike glycoprotein to its receptor angiotensin-converting enzyme 2 (ACE2) but concerned has arose for the continuous expressing of ACE in affected patient especially patient with pregnancy as this might increase the susceptibility of the patient although there is no strong evidence for it involvement for susceptibility of the affected patients. Despite the continuous evolving and dynamics on the literature of COVID-19, using the existing knowledge, possible drug target have been identified for the development of the effective vaccine. Since there is no effective therapeutic drug for the current pandemic, drug repurposing might be a viable strategy and specific prophylaxis regimen should be provide to reduce the toxicity on the affected patients and the clinical trial should be based on the specificity and efficacy of the drug. This review provide information on the Novel invention and new guidelines or protocol for SARS-COV-2.