Novel Targets and Drug Delivery System in the Treatment of Postoperative Pain: Recent Studies and Clinical Advancement.

Pain is generated by a small number of peripheral targets. These can be made more sensitive by inflammatory mediators. The number of opioids prescribed to the patients can be reduced dramatically with better pain management. Any therapy that safely and reliably provides extended analgesia and is flexible enough to facilitate a diverse array of release profiles would be useful for improving patient comfort, quality of care, and compliance after surgical procedures. Comparisons are made between new and traditional methods, and the current state of development has been discussed; taking into account the availability of molecular and cellular level data, preclinical and clinical data, and early post-market data. There are a number of benefits associated with the use of nanotechnology in the delivery of analgesics to specific areas of the body. Nanoparticles are able to transport drugs to inaccessible bodily areas because of their small molecular size. This review focuses on targets that act specifically or primarily on sensory neurons, as well as inflammatory mediators that have been shown to have an analgesic effect as a side effect of their anti- inflammatory properties. New, regulated post-operative pain management devices that use existing polymeric systems were presented in this article, along with the areas for potential development. Analgesic treatments, both pharmacological and non-pharmacological, have also been discussed.

Antiarthritic Activity and Inflammatory Mediators Modulation Effect of Traditional Ajmodadi Churna on Arthritis Experimental Model.

Objectives: The study was designed to evaluate anti-arthritic activity of Ajmodadi Churna (AC) and its effect on Complete freund's adjuvant (CFA)-induced arthritis in Wistar rats. Methods: Arthritis was induced by injecting 0.2 mL CFA into sub plantar surface of left hind paw. Test sample AC-1 and AC-2, 200 and 400 mg/kg, respectively was given to the animals for 21 consecutive days. The increase in swelling was observed after induction of arthritis. The paw edema was measured on 0, 3, 7, 14 and 21 day using Vernier calliper after the induction of arthritis. The collected blood samples further used for the estimation of red blood cells (RBC), white blood cells (WBC), erythrocytes sedimentation rate (ESR), and hemoglobin (Hb), using hematology analyzer. Serum concentration of IL-6 and TNF-α were also measured using rat ELISA kits. Results: Results showed that a significant reduction in paw edema was observed in AC-2 treated rats. The paw edema was restored on day 21 was 4.48 mm for AC-2, which is near to the control group. The arthritis score in treated rats was found to be considerably lower than in the control group i.e. 0.83 for AC-2 and 1.50 for AC-1. A decrease in levels of RBC and hemoglobin were observed in arthritic rats. Inflammation was significantly reduced and serum levels of IL-6 and TNF-α were lowered after treatment with the test drug. Conclusion: It can be concluded from the study that AC possess significant anti-arthritic activity. Furthermore, this condition was linked to a reduction in abnormal humoral immune responses.

Therapeutic potential and novel formulations of ursolic acid and its derivatives: an updated review.

Plants produce biologically active metabolites that have been utilised to cure a variety of severe and persistent illnesses. There is a possibility that understanding how these bioactive molecules work would allow researchers to come up with better treatments for diseases including malignancy, cardiac disease and neurological disorders. A triterpene called ursolic acid (UA) is a pentacyclic prevalent triterpenoid found in fruits, leaves, herbs and blooms. The biological and chemical aspects of UA, as well as their presence, plant sources and biosynthesis, and traditional and newer technologies of extraction, are discussed in this review. Because of its biological function in the creation of new therapeutic techniques, UA is a feasible option for the evolution and medical management of a wide range of medical conditions, including cancer and other life threatening diseases. Despite this, the substance's poor solubility in aquatic environments makes it unsuitable for medicinal purposes. This hurdle was resolved in many different ways. The inclusion of UA into various pharmaceutical delivery approaches was found to be quite effective in this respect. This review also describes the properties of UA and its pharmacokinetics, as well as therapeutic applications of UA for cancer, inflammatory and cardiovascular diseases, in addition to its anti-diabetic, immunomodulatory, hepatoprotective and anti-microbial properties. Some of the recent findings related to novel nano-sized carriers as a delivery system for UA and the patents related to the applications of UA and its various derivatives are covered in this review. The analytical study of UA, oleanolic acid and other phytoconstituents by UV, HPLC, high-performance thin-layer chromatography and gas chromatography is also discussed. In the future, UA could be explored in vivo using various animal models and, in addition, the regulatory status regarding UA needs to be explored. © 2023 Society of Chemical Industry.

Indian spices: past, present and future challenges as the engine for bio-enhancement of drugs: impact of COVID-19.

Spices are natural plant products enriched with the history of being used as herbal medicine for prevention of diseases. India is also known as the 'Land of Spices'. Out of 109 spices recognized by the International Organization for Standardization (ISO) more than 52-60 spice crops are grown in India. The major spices exported by India are turmeric, cumin, coriander, fenugreek, peppers, etc. The Indian spices are divided into three era viz. early period, middle age and early modern period. Spices are used in beverages, liquors, and pharmaceutical, cosmetic and perfumery products. The major issue with spices is their handling and storage. This review article mainly focuses on two aspects: at the outset the handling and storage of the spices is an essential factor as spices are available in different forms like raw, processed, fresh, whole dried, or pre-ground dried. Therefore, the need of processing, packaging, storage and handling of the spices is important as the deterioration of spices can lead to the loss of therapeutic activity. Furthermore, many herbal constituents have the capability to enhance the bioavailability of drugs. Therefore, an attempt has been made to throw a light on the bioenhancer activity and therapeutic activity along with their mechanism of action of some Indian spices which are regularly used for cooking purpose on a daily basis to enhance the taste of food. The spices suggested by ministry of AYUSH which is relevant to its medicinal and biological property in treatment and prevention from COVID-19 are discussed. © 2022 Society of Chemical Industry.

To Assess the Technical Feasibility of Ultrasound Lumbar Sympathetic Block with Electrical Stimulation Needle in Out-of-Plane Needle Orientation: A Prospective Interventional Study.

OBJECTIVE: We describe the technical feasibility of a new technique of ultrasound lumbar sympathectomy validated by fluoroscopy. DESIGN: Prospective interventional study. SETTING: Pain block area. SUBJECTS: Thirty patients with peripheral arterial disease with pain at rest (numerical rating score [NRS] ≥3) were recruited. METHODS: In the lateral position, a curved probe (FUJIFILM SonoSite Edge, Bothell, WA, USA, 2-5 MHz) was placed transversely at the iliac crest. An electrical stimulation needle was inserted out of plane, below the lower pole of the kidneys, directed anterior to the vertebral body below. When the needle tip was not visualized, a current of 2.0 A was applied. Patients' quadriceps contractions, ultrasound psoas contractions, and bone contact guided needle placement, which was confirmed on fluoroscopy. Other parameters noted were the number of needle insertions, vertebral level, pain NRS at baseline and at 4 hours, 24 hours, 1 week, and 2 weeks after block, temperature rise, and any other complications. RESULTS: In all patients, the needle tip was correctly placed in one to three attempts. In 73% of patients, the needle tip was at L3. Baseline pain NRS was 8 (interquartile range 7-8), which decreased to 2 (interquartile range 2-3) at 1 week after the procedure, and it was maintained in this range until 2 weeks later. A temperature rise of >2ºC was noted in all patients. CONCLUSION: Ultrasound lumbar sympathectomy can be performed safely in patients with peripheral arterial disease by an out-of-plane approach in the lateral patient position with an electrical stimulation needle. Before injection of the drug, aspiration of blood should be ruled out in view of the possibility of aortocaval injection.

A review on corona virus and treatment approaches with Allium sativam.

BACKGROUND: Recently reported cases of Covid-19 globally remind us that new diseases are coming while we are unable to provide the treatment for the same. The entire world is facing this viral attack; deaths are increasing day by day as well as infected patients too. Today, in the period of this disease, can we go to the shelter of our traditional medicines? MAIN BODY: In this article, we have taken medicines related to corona and conceptualized their mechanism, which gave us a chance to understand Garlic's mechanism of action, how Garlic can be a weapon in the lane with this disease. This article also tells how we can treat new diseases with our traditional herbs if no modern medicine has been discovered yet. CONCLUSION: The present review is based on the structure of the virus and the targeted site for the drug discovery process with important constituents of Allium sativam. The review work also explains the allicin chemical constituent of Allium sativam which has targeted therapeutic sites related to Covid-19.

Acaricidal activity and clinical safety of arecoline hydrobromide on calves infested with cattle tick Rhipicephalus microplus (Acari: Ixodidae).

The objective of the present study was to determine the acaricidal activity of arecoline hydrobromide against cattle tick Rhipicephalus microplus infesting calves. in vivo efficacy of arecoline emulsified with polysorbate-80 (2%) was evaluated using ear bag method with the effective dose of 12.5 mg/mL applied on ear pinna of calves infested with ticks. Control group received polysorbate-80 (2%) after larvae infestation, however, reference group received deltamethrin (0.5 %). The experiment was continued for six days (144 h) and treatment of drug was given twice a day. Daily observation of calves was done to count the number of ticks after treatment. Acute dermal toxicity study for test drug was performed on wistar rats. Clinical safety of arecoline was determined by examining hematological profile and skin irritancy assay for calves infested with ticks. Results showed that arecoline significantly (p < 0.01) reduced the number of ticks attached to ear pinna of calves. Fewer number of ticks remained on calves skin at 120 h and 144 h were 8.09 and 6.21, respectively after treatment with arecoline in comparison to control group. Treatment of animals with arecoline hydrobromide significantly (p < 0.01) restored the hematological profile of animals as hemoglobin (Hb) level was 9.01 g/100 mL, PVC was 29.24 %, TEC and TLC were 5.23 and 7.19 106/cumm, respectively as compared to the control group having Hb 9.48 g/100 mL, PVC 31.60 %, TEC 5.64 106/cumm and TLC 7.27 106/cumm. Arecoline showed no toxicity while applied on wistar rats. The drug was mild irritative for an initial 20 min to the calves after that no redness or erythema was seen on the skin of the animals. Thus, arecoline hydrobromide may be an effective alternative to be used as herbal ectoparasiticide for the eradication of R. microplus ticks.

First report on efficacy of Citrus limetta seed oil in controlling cattle tick Rhipicephalus microplus in red Sahiwal calves.

The objective of the study was to evaluate the acaricidal activity of Citrus limetta seed oil (CLO) for controlling the cattle tick Rhipicephalus microplus. C. limetta seeds were collected as a waste product from different juice corners. CLO was obtained after extraction of seeds on soxhlet apparatus using n-hexane as solvent. It was characterized through Gas Chromatography-High Resolution Mass Spectroscopy (GC-HRMS) to determine the presence of active constituents. In vitro bioassays were performed using adult immersion test (AIT) and larval packet test (LPT). In vivo acaricidal efficacy of CLO was performed on red Sahiwal calves using ear bag method. Clinical safety of CLO was evaluated by observing haematological parameters and skin irritancy assay. Results of GC-HRMS showed that mainly fatty acids such as linoleic acid, stearic acid, oleic acid, palmitic acid, and linolenic acid were present in the CLO. CLO in the concentration of 125 mg/mL (CLO8) exhibited 100 % mortality in both AIT and LPT. CLO significantly (p < 0.001) reduced the number of ticks from 35 to 5.05 and 3.24 on 144 h after treatment with CLO7 and CLO8, respectively. CLO was found clinically safe without producing erythema and edema on skin. Haematological parameters such as haemoglobin (11.48 g/100 mL), total leucocytes count (4.32 106/cumm), total erythrocytes count (6.80 106/cumm), and packed cell volume (34.39 %) were normal and controlled. CLO may be used as effective and safe drug therapy for controlling R. microplus ticks.

Rhipicephalus microplus (acari: Ixodidae): Clinical safety and potential control by topical application of cottonseed oil (Gossypium sp.) on cattle.

The present study was performed to determine the acaricidal activity of the cottonseed oil (CSO) against cattle tick Rhipicephalus microplus. CSO was analyzed using Gas Chromatograph with high-resolution Mass Spectrometer (GC-HRMS) to identify the presence of active compounds. In vitro bioassays were performed using larval packet test (LPT) and adult immersion test (AIT) by taking different concentrations of CSO (i.e. 0.1, 0.5, 1.5, 2.5, 5, 7.5, 10 and 12.5%). In vivo acaricidal activity of CSO was evaluated by its topical application on red Sahiwal calves for 144 h. Clinical safety of CSO was evaluated by performing skin irritancy test and examination of hematological profile of calves'. GC-HRMS analysis of CSO revealed the presence of many fatty acids including oleic acid, lauric acid, palmitic acid, stearic acid and other components. Results exhibited that all the concentrations of CSO were effective in reducing the number of ticks and their growth. However, CSO at concentrations of 10% (CSO7) and 12.5% (CSO8) exhibited 100% mortality of R. microplus larvae and adults in LPT and AIT, respectively. In vivo acaricidal assay revealed that CSO7 and CSO8 shown 85% and 89% inhibition of ticks, respectively on calves after 144 h as compared to the control group. CSO was clinically safe on calves' skin with mild erythema up to 20 min. Hematological profile of calves revealed no sign of toxicity after treatment with CSO. Thus, CSO can be used as an alternative and safe drug therapy against R. microplus.

Current and Future molecular mechanism in Inflammation and Arthritis.

Inflammation is an immune response of the human body but excessive inflammation is taken as a major factor in the development of many diseases including autoimmune disorders, cancer and nerve disorders etc. In this regards the need is to suppress the inflammatory response. Suppression of extra or imperfect inflammatory response is not a big deal provided there is an exact knowledge of particular target in the body. Recent advancements in Pharmacological aspect made the therapy with improved outcomes in number of patients. Anticytokine therapy might be one of the important and novel approaches for inflammation and Arthritis. This can be achieved only when we go through the pathophysiology of expression and identification of mediators. Let's take an example of cytokine like interleukins (IL), chemokines, interferons (INF), tumor necrosis factors (TNF-α), growth factors, and colony stimulating factors) release pathway which is a major signalling protein in inflammatory response. In the present study we have reviewed the recent pharmacological therapeutic advancement, inflammatory mediators, receptors, and major signalling pathways. Such information will not only provide the idea about the mechanism of action of Pharmaceuticals and molecular targets but also it provides a new aspect for drug designing and new corrective approaches in existing clinical medicines. This study will be a source of good information for the researchers working in the area of drug designing and molecular Pharmacology especially in anti-inflammatory and anti arthritic medicines for target based therapy.

Nicotine Addiction: Neurobiology and Mechanism.

Nicotine, primary component of tobaco produces craving and withdrawal effect both in humans and animals. Nicotine shows a close resemblance to other addictive drugs in molecular, neuroanatomical and pharmacological, particularly the drugs which enhances the cognitive functions. Nicotine mainly shows its action through specific nicotinic acetylcholine receptors located in brain. It stimulates presynaptic acetylcholine receptors thereby enhancing Ach release and metabolism. Dopaminergic system is also stimulated by it, thus increasing the concentration of dopamine in nuclear accumbens. This property of nicotine according to various researchers is responsible for reinforcing behavioral change and dependence of nicotine. Various researchers have also depicted that some non dopaminergic systems are also involved for rewarding effect of nicotinic withdrawal. Neurological systems such as GABAergic, serotonergic, noradrenergic, and brain stem cholinergic may also be involved to mediate the actions of nicotine. Further, the neurobiological pathway to nicotine dependence might perhaps be appropriate to the attachment of nicotine to nicotinic acetylcholine receptors, peruse by stimulation of dopaminergic system and activation of general pharmacological changes that might be responsible for nicotine addiction. It is also suggested that MAO A and B both are restrained by nicotine. This enzyme helps in degradation dopamine, which is mainly responsible for nicotinic actions and dependence. Various questions remain uninsurable to nicotine mechanism and require more research. Also, various genetic methods united with modern instrumental analysis might result for more authentic information for nicotine addiction.

Comparison of Macintosh, McCoy, and Glidescope video laryngoscope for intubation in morbidly obese patients: Randomized controlled trial.

OBJECTIVES: The aim of the study was to compare time to intubation and glottic visualization between Macintosh, McCoy, and Glidescope video laryngoscope (GVL) in morbidly obese patients. METHODOLOGY: Forty-five American Society of Anesthesiologists I-III morbidly obese patients were randomized into three groups of 15 each and time to intubation, Cormack-Lehane grading, and Intubation Difficulty Score (IDS) were compared. RESULTS: GVL took more time to intubate (TTI) compared to Macintosh and McCoy laryngoscope (P = 0.0001). Overall IDS were similar between the groups. CONCLUSION: To conclude, GVL takes longer TTI with no added advantage in IDS and hemodynamic response to intubation in morbidly obese patients. McCoy is only as effective as Macintosh and hence Macintosh laryngoscope should be laryngoscope of choice due to its widespread availability and familiarity.