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Pharmacoeconomics: Open Access

ISSN: 2472-1042

Open Access

Article in Press

Natural Products and Pharmacoeconomics-2 (2021)

    Special Issue Article Pages: 1 - 2

    Novel therapeutic anticancer property of Vernonia amygdalina Delile towards the treatment of prostate cancer

    Clement G. Yedjou *1, Alo A. Richard1, Paul B. Tchounwou2

    Prostate cancer is one of the common cancers in males and its incidence keeps increasing globally. Approximately 81% of prostate cancer is diagnosed during the early stage of the disease. The treatment options for prostate care include surgery, radiotherapy, and chemotherapy, but these treatments often have side effects that may result to poor quality of life such as impotence or decrease bowel function. Our central goal is to test the anticancer activity of Vernonia amygdalina Delile (an edible medicinal plant that is relatively inexpensive, nontoxic, and virtually without side effects) for the prevention of prostate cancer using human adenocarcinoma (PC-3) cells as a test model. To address our specific goal, PC-3 cells were treated with Vernonia amygdalina Delile (VAD). Cell viability and cell morphology was analyzed by acridine orange and propidium iodide (AO/PI) dye using the fluorescent microscope. DNA damage was evaluated by the comet assay. Cell cycle arrest and cell apoptosis was evaluated by Flow Cytometry assessment. Nucleosomal DNA fragmentation was detected by DNA ladder assay. Data obtained from the AO/PI dye assessment indicated that VAD significantly reduced the number of live cells in a dose-dependent manner, showing a gradual increase in the loss of viability in VAD-treated cells. Similar result was previously obtained by the MTT assay. We observed a significant increase in DNA damage in VAD-treated cells compared to the control group. Flow cytometry data showed that VAD induced cell cycle arrest at the G0/G1 checkpoint. Flow cytometry data also showed that VAD induced caspase-3 activation in treated cells compared to the control group. We observed the formation of the DNA ladder in gel electrophoresis by induction of apoptosis in PC-3 cells treated with VAD. These results suggest that inhibition of cancer cell growth, induction of DNA damage, cell cycle arrest at the G0/G1 checkpoint, and apoptosis through caspase-3 activation and nucleosomal DNA fragmentation are involved in the therapeutic efficacy of VAD as anticancer candidate towards the prevention and/or treatment of prostate cancer.

    Special Issue Article Pages: 3 - 3

    GC-MS analysis of Myrtus communis extract and its antibacterial activity against Gram-positive bacteria

    Mushtaq A. Mir *, Nasreena Bashir , Abdulkhaleg Alfaify , and Mohammed D. Y. Oteef

    Myrtus communis is a typical plant of Mediterranean area. The different parts of this plant such as berries, branches, and leaves have been used worldwide as a traditional/folk medicine for the treatment of various ailments and diseases. Ethanolic leaf extract of the plant was prepared and its effect on bacterial growth was investigated. The ethanolic extract showed strong inhibitory effect against Gram-positive and acid-fast bacteria with significant inhibition-zone size (9–25mm), MIC (4.87–78 μg/ml), as well as MBC (0.3–20 mg/ml). However, no effect was observed on the growth of Gram-negative bacteria. The growth inhibition was found to be associated with the damage of cell wall as the extract-treated cells were sensitive to cell wall-targeting antibiotics and displayed the cell wall damage-depicting morphological defects. GC-MS analysis confirmed the presence of novel compounds in addition to the most representative compounds of the essential oils/extracts of M. communis of other country origins. These results demonstrate that M. communis leaf extract could be the source of compounds to be used for the treatment of Gram-positive bacterial infections. This is the first report, which provides insights into the mechanism of action of the extract in inhibiting the growth of Gram-positive bacteria.

    Special Issue Article Pages: 4 - 4

    Bioactive component analysis of dices of pomegranate fruits in different genotypes

    Sibel Bayıl OÄ?uzkan *1,Elif Sine Düvenci 2,Halil Ibrahim UÄ?raÅ? 2

    Pomegranate fruit is a type of fruit belonging to the family of Lythraceae, consisting of shell, kernel, grains and dice. In this study, pomegranates of 3 different genotypes (local name : deve di?i, hicaz and nuz ek?isi) harvested (October-December), which are widely cultivated in the province of Gaziantep, O?uzeli, were collected, and after identification, the dice sections were removed and dried in the shade. Total antioxidant and total oxidant levels, animicrobial activities, DNA protective activity and total flavanoid and total phenolic content were determined in 18 extracts in 3 different solvents (methanol, ethanol and DMSO) with solid-liquid extraction. Kirby-Bauer disc diffusion method was used to determine antimicrobial properties. According to the results obtained, 100% of Escherichia coli, Stenotrophomonas maltophilia, Staphylococcus aureus strains were resistant to all membrane extracts. While antioxidant levels of all membrane extracts were found highly and oxidant levels were found to be low. It was determined that the extracts have the potential to protect DNA against oxidative damage caused by UV and H2O2. Total phenolic determination by Folin-Ciocalteu method; Total flavonoid amount was measured by AlCl3 using colorimetric method. Compared to the solvent and extraction methods used, high results were obtained in both phenolic and flavonoid determinations in all extracts, although they differed slightly among themselves. While the pomegranate fruit is consumed as food, the dice and shell parts are discarded. According to our study results, it is thought that alternative new products that can be used in complementary medicine can be obtained from pomegranate membranes that have a rich bioactive composition.

    Special Issue Article Pages: 5 - 6

    Nanoliposomes of supercritical carbon dioxide extract of small cardamom seeds: A potent hypocholesterolemic agent

    Paramita Bhattacharjee *1, Kaninika Paul 1, NilendraChatterjee 2, Tapan KumarPal 3

    Oral administration of 1,8-cineole-rich supercritical carbon dioxide (SC-CO2) extract of small cardamom seeds in hypercholesterolemic Wistar albino rats resulted in restoring normal total cholesterol (TC) levels in the animals. These findings prompted us to encapsulate the aforesaid extract as nanoliposomes to enhance its shelf stabilitiy. Nanoliposome of the extractwas characterized and itsin vivo hypocholesterolemic efficacy was assessed in triton-X treated hypercholesterolemic rats. Atorvastatin served as the positive control in the in vivo study. PEGylated nanoliposomes of small cardamom seed extract (SN) were formulated using soya phosphatidylcholine and Tween 80 (composition standardized) using ultra-sonication (probe) technology. Entrapment efficiency of spherical SN (dp= 76.93 nm) was 84.20% possessing negative zeta potential value<30. The antioxidant potency and shelf stability of SN (T1/2 = 192 days at 4 ± 1 °C) were appreciably higher than that of the native extract and exhibited in vitro sustained release of the spiceutical from the same. The liposomes had thermal stabilities up to 250 °C and successful binding among their chemical constituents were confirmed by FT-IR and XRD spectra. Reduction in TC levels in rats co-administered with liposomes (550 mg/kg b.w.) and triton-X were comparable to that of atorvastatin-administered rats on day 35. Moreover, SN (550 mg/kg b.w.) exhibited inhibitory effects on HMG-CoA reductase activity in the animals. This study established nanoliposomes of small cardamom seed extract as natural alternative of statin in redressing hypercholesterolemia.

    Special Issue Article Pages: 7 - 8

    The Anti-inflammatory effects of the Jamaican species of Cymbopogon citratus (lemon grass) and Croton linearis (wild rosemary) plant extracts on carrageenan-induced inflammation

    A. Jacob *1, L.A.D Williams 2, Anthony Webly 1, Michael Heron 1, E.A Thomas 1

    Inflammation occurs in response to injury and if left untreated can lead to several diseases including arthritis. In Jamaican folklore practice plant extracts have been traditionally used to treat inflammatory conditions including rheumatoid arthritis and asthma. This is the first preliminary scientific investigation of the anti-inflammatory effects of extracts from the Jamaican species of Croton linearis (wild rosemary) and Cymbopogan citratus (lemon grass) leaves on carrageenan-induced rat paw edema. The methods used involved testing of plant extracts on inflammation induced by carrageenan lambda on the rat paw model. 0.1ml of 1% Carrageenan lambda in saline solution (0.9%) was injected into the plantar region of the right hind paw of all groups to induce inflammation. Hexane extract (50mg/kg) of Croton linearis screened by BSA assay represents a sample inhibiting denaturation greater than 0%. Findings show that Croton linearis extract and aspirin (NSAID) shows comparable efficacy in reducing rat paw oedema (p< 0.05)(n=18 Sprague Dawley rats). This extract might be blocking the COX enzymes, with emphasis on COX-2 actions inflammation. Lemon grass extract 400 mg/kg showed reduction in paw volume (p < 0.001), 200 mg/kg extract (p <0.01), saline group showed no significance compared to aceclofenac group (p<0.05), n=24. In concluding extracts of both Wild rosemary and lemon grass showed comparable efficacy to aspirin and aceclofenac in reducing the inflammatory response induced by carrageenan lambda. This data indicates that the extracts of Jamaican species of our samples contain components with anti-inflammatory potential. We are hoping to assess if the extracts are arresting inflammation at the early stage where there is release of histamine, 5-hydroxytrptamine and bradykinin or in in the late phase where prostaglandins are detectable (Prakash et al., 2011). Further work needs to be done to assess for toxicity and to purify the extracts to ensure safety.

    Traditional Medicine and Pharmacoeconomics (2021)

      Special Issue Article Pages: 1 - 1

      Biotransformation monitoring, protein-ligand interactions and In-cell NMR spectroscopy in natural products research

      I.P. Gerothanassis

      A critical overview of the following developments of NMR spectroscopy will be summarized:
      (a) rapid ‘in situ’ monitoring of enzymatic reaction products [1], and enriching the biological space of natural products, through real time biotransformation monitoring in the
      NMR tube. Investigation of interactions with the intrinsically disordered protein α-synuclein which is abundant in the human brain and a relevant target for neurodegenerative
      diseases [2].
      (b) The combined use of saturation transfer difference (STD), Tr-NOESY and INPHARMA (Interligand Noes for PHArmacophore MApping) NMR techniques for mapping
      interactions, specific binding sites and structure elucidation of lipids with non-labelled serum albumin and the anti-apoptotic protein Bcl-2 [3,4].
      (c) Application of in-cell NMR analytical methodology in the monitoring of the interaction of ligands with Bcl-2 inside living human cancer cells without requiring prior isotopic
      labeling of the target protein. STD and Tr-NOESY NMR were employed to evaluate the direct binding of the ligand to the nonlabelled Bcl-2 protein intracellularly [5], which
      was further validated in vitro. This approach has proved a very promising strategy for the real-time screening of the interaction profiling of drugs with their therapeutic targets
      in their native cellular environment in living eukaryotic cells, paving the way to the new field of intracellular rational drug design.

      Special Issue Article Pages: 2 - 2

      Ambrosin: a possible alternative for curcumin in alleviation of lipopolysaccharide induced memory impairment

      Mohammed N.A. Khalil * 1,2

      Despite its poor bioavailability, curcumin is a promising natural polyphenol targeting NF-κβ. NFκβ is a target for new therapeutics because it plays a pivotal role in the
      pathophysiology of Alzheimer disease (AD). In contrast, ambrsoin which is a potent NF-κβnhibitor, is scarcely studied in AD models. The current work aims to assess
      the efficacy of ambrosin as a possible remedy for AD. In silico studies showed that bioavailability and BBB permeability could be favorable for ambrosin over curcumin.
      Ambrosin was isolated and purified from extract of the traditional herb Ambrosia maritima. Memory impairment was induced in mice by single intraperitoneal injection of LPS
      (0.4 mg/kg). Treated groups received curcumin (100 mg/kg) or ambrosin at doses (5 or 10 mg/kg) for 7 days. Mice in treated groups showed a significant improvement in
      memory functions during Morris water maze and object recognition tests. Curcumin and ambrosin (10 mg/kg) inhibited the upsurge of NF-κβ65 transcript and protein levels.
      Consequently, downstream pro-inflammatory and nitrosative mediators were inhibited, namely, TNFα IL-1βCOX-2 and iNOS. BACE1 was inhibited, thereby reducing
      amyloid plaques (Aβ) deposition and eventually reducing inflammation and apoptosis of neurons as revealed by immunohistopathological examination. In conclusion,
      ambrosin can be repurposed as AD remedy after further pharmacokinetic/pharamacodynamic assessments. It could serve as an additional lead drug for AD therapeutics.

      Special Issue Article Pages: 3 - 3

      Food safety research at VSU in the US

      Chyer Kim1,* Rehab Almuqati2, Abeer Fatani2, Rahemi Alireza1, Paul Kaseloo2, Crystal Wynn3, Theresa Nartea4, Eunice Ndegwa1 and Laban Rutto1

      As farmers’ markets have increased in size, scope and complexity, so have the food-safety challenges and implications. Most products sold at farmers’ markets receive minimal
      to no treatment, which increase their potential microbial risks. The aim of this study was to assess the prevalence and characterization of foodborne pathogens on select fresh
      produce procured from farmers’ markets in Central Virginia. A total of 138 samples produced by 15 farms and sold at 9 registered farmers’ markets were obtained between March
      and November 2017. The highest level of coliforms was found in cilantro with 5.8 log MPN/g. Prevalence of Campylobacter, E. coli, and Listeria were observed. A total of 46
      bacterial isolates consisted of Campylobacter, E. coli, and Listeria were tested for their susceptibility to 12 antimicrobials. Ampicillin showed the highest frequency of resistance
      among Campylobacter (100%) and E. coli (47.8%) isolates while nalidixic acid showed the highest resistance in Listeria isolates (72.7%). At least 17% of each Campylobacter,
      E. coli, and Listeria isolates exhibited resistance to three or more categories of antimicrobials, meeting criteria for multidrug resistance (MDR). No isolates had matching pulsedfield
      gel electrophoresis (PFGE) profiles demonstrating that the isolated pathogens had a high degree of genomic diversity. This study demonstrated a potential health hazard
      arising from farmers’ market-acquired fresh produce and emphasizes the importance of good agricultural and handling practices to prevent foodborne illness. Continued
      research is needed to determine and intervene the cause(s) of the observed prevalence and to support the healthy development of food products sold at farmers’ markets.

      Special Issue Article Pages: 4 - 4

      Selected fungal natural products with antimicrobial properties

      Dorota Jakubczyk

      Natural products are an invaluable source of new drugs as they constitute more than two-thirds of clinically used antibiotics and 50% of anticancer drugs. Fungi
      produce many secondary metabolites which display high bioactivity. For example, toxic ergot alkaloids produced by filamentous fungi growing on rye poisoned
      thousands of people and livestock throughout the Middle Ages. However, their later medicinal applications, followed by the discovery of the first class of antibiotics,
      penicillins and other drugs of fungal origin, such as peptidic natural products, terpenoids or polyketides, have altered the historically negative reputation of fungal
      “toxins”. The development of new antimicrobial drugs is currently a major global challenge, mainly due to antimicrobial resistance phenomena. Therefore, the
      structures, biosynthesis and antimicrobial activity of selected fungal natural products will be presented.

      Special Issue Article Pages: 5 - 6

      Hijama practices and the perceived health benefits among the people of Al-Qassim Region, Saudi Arabia

      Khawla Al-luhaidan *, Prarthana M S

      Statement of the Problem: Hijama the traditional Arabic name for wet cupping therapy means “to return to the normal size”, is a form of alternative medicine that
      has been in practice for thousands of years and was adopted by many different cultures. Hijama being a bloodletting technique involves cupping, puncturing and
      cupping (CPC) method. Cups are applied through vacuum, skin is lacerated, the cups are repositioned and the blood is drawn so that the morbid substances are
      evacuated. Arabic medical literature has reported Hijama being effective in treating many diseases differing in etiology and pathogenesis. The purpose of this study
      is to determine the knowledge, attitude, practices and effectiveness of Hijama among the population practicing Hijama, in Qassim, Saudi Arabia.
      Methodology: 201 participants practicing Hijama were enrolled in the study. Data was collected using a self-administered online questionnaire in Arabic and
      analyzed using statistical software EpiInfo7.
      Findings: Most of the study participants were female 70%. 33.8% were in the age group of 21 to 30 years. About 39% of them have a bachelor’s degree. Hijama as
      modality of treatment was used for: back or shoulder or neck pain 46.7% (p=.014), headache and migraine 29.3%, joint pain 22.9% (p=.02), hypersomnia 16.4%.
      Hijama was performed by traditional healers in 14% of the participants and at Hijama centers in 64% of the participants. About 72% of the participants notice
      effectiveness. The effectiveness increased with increase in frequency of Hijama (p=.009). 7% of them had suffered complications.
      Conclusion and Significance: The study reveals Hijama as a simple, effective, economic alternative medicine to treat chronic aches and pains with minimal side effects
      and can be more beneficial when compared to the present use of non-steroidal anti-inflammatory drugs with relatively higher side-effects. Future research is needed to
      support its therapeutic benefits.

      Effect of Alternative Medicine and Pharmacoeconomics (2021)

        Special Issue Article Pages: 1 - 1

        Eficacy of fibromyalgia treatment using Bach Flower Therapy: Preliminary results

        Jozélio Freire de Carvalho,1,2* Cassia Jesus Rocha,2 Natasha Lima Bastos de Queiroz2, Jordan Campos2

        Statement of the problem: Fibromyalgia (FM) is a prevalent disease and often presents symptoms of anxiety and depression. Bach florals (BF) are widely used to treat such manifestations. No studies on the use of BF in FM were found.
        Objective: To evaluate the effects of BF (Rescue) in FM patients.
        Patients and methods: 6 patients and 6 healthy controls were included. They were evaluated at pre-intervention and after 60 days of BF using. Demographic data, anxiety and depression were evaluated by Beck inventories; sleep quality by the Pittsburgh scale and symptoms of dysbiosis by symptoms form.
        Results: The median age was 60 years old (22-77) in patients and 41 (40-43) years old in controls. The disease duration was 3 years (4 months -10 years old). Caucasian race was 33% in the patient group and 66% in the controls. There was a statistically significant reduction between the Beck Anxiety Questionnaire before and after 60 days [16 (6-42) vs. 10 (2-27), p=0.05), Beck Depression Questionnaire before and after 60 days [16 (8-52) vs. 10 (6-35), p=0.02) and dysbiosis questionnaire before and after 60 days [18 (10-27) vs. 15 .5 (7-27), p=0.03). Regarding the sleep form, no significant differences were observed before and after BF.
        Conclusion and significance: Treatment with Bach flower in patients with fibromyalgia seems promising, as it reduces tender points, symptoms of depression and anxiety, as well as improvement of symptoms of dysbiosis.

        Special Issue Article Pages: 2 - 2

        A single case study on Atopic Eczematous Dermatitis with special reference to Vicharchika

        Anjana L.Siddapur

        “Kushnaati vapuh iti kustah” that which disfigures or deforms a person’s physique is Kusta. One such common type of Kusta which is commonly encountered by Ayurveda physicians in day today practice is Vicharchika, which is characterized by Pidaka (vesicles), Srava (oozing), Shyava varna (discolouration) and Kandu (itching). Susruta samhita also gives a reference of ruksha Vicharchika which is also seen in clinical practice. Treatment in contemporary science restricts to the hindrance of the complaints but not from the route and condition is seen to reappear inspite of repeated management using antihistamines and topical steroid applications. A patient presented with clinical features vesicles, erythematous skin lesions and discharge with intense itching at the posterior part of lower limbs, forearms, front and back of chest, abdomen & inguinal region. He was treated with Virechana and Agada formulations, considering the history. Dooshivisha in the samprapti of that condition. Results were encouraging and remarkable.

        Special Issue Article Pages: 3 - 4

        Phenolic characterization and biological potential of Pterospartum tridentatum phenolic-rich extracts

        Ana C. Gonçalves,1* Ana R. Nunes,1 Manuel Simões 2, Gilberto Alves 1, Luís R. Silva 1

        For a long time, fruits, vegetables and natural plants have been a target of many studies and their consumption has been increasingly encouraged owing to their nutritional value and abundance of nutritional and bioactive compounds, known for their protective effects. Among plants, and although Pterospartum tridentatum, an endemic plant from the northwest of the Iberian Peninsula and Morocco, is largely used in culinary, their phytochemical profile and therapeutic effects remain little known. Therefore, we decided to determine the phenolic composition of infusions and hydroethanolic extracts of P. tridentatum by high-performance liquid chromatography method coupled to a diode array detector analysis. Furthermore, we also evaluated their biological potential, namely antioxidative and antiproliferative effects, and capacity to inhibit α-glucosidase activity. In total, 13 phenolics were found; genistein was the major one, comprising 36.8 and 20.2% of total phenolics in infusion and hydroethanolic extracts, respectively. Regarding the biological potential, the hydroethanolic extract was the most active against 2,2- diphenyl-1-picrylhydrazyl? and in inhibiting α-glucosidase activity. On the other hand, the infusion proved to be a remarkable free radical scavenger against superoxide and nitric oxide free radical species, and in protecting human erythrocytes facing peroxyl radicals. Both extracts also showed cytotoxic selectivity for human epithelial colorectal adenocarcinoma (Caco-2) cells when compared to the NHDF normal cell line, inhibiting its growth in a dose-dependent manner. Furthermore, they also showed protective effects against oxidative stress induced by tert-butyl hydroperoxide on these cancer cells. Overall, the obtained data suggest that these extracts may be interesting to enrich nutraceutical, dietary and food supplements, and pharmaceutical drugs; however, more studies are needed to unravel ensure safe dosage of both extracts and to incite their use in new formulations, functional foods, pharmaceutical preparations and/or food additives.

        Special Issue Article Pages: 5 - 5

        Management of recurrent urethral stricture by Uttar Basti: A case study

        Alok Kumar

        Urethral stricture is the very common problem occurred in the patients after prolonged urinary tract infection, urethral injury or post-surgical intervention performed through per urethral. In Ayurvedic literature urethral stricture may be correlated as mutrotsanga mentioned in Sushruta Samhita. One of the prime literature in Ayurvedic surgery. Now day as the science advances with technology various surgeries like urethrolithotomy, Trans urethral removal of prostate (TURP), cystoscopy are performed with telescopic instruments like cystoscope. During these procedure the urethral lining of mucosa get injured and later on develop the scary fibrosis that lead the urethral stricture in the urethra. The most common way to overcome this problem is surgery i.e. urethroplasty. But the recurrence rate is good enough to think the alternative. In Ayurvedic literature uttarbasti is the procedure in which some medicinal preparation are introduced per urethral. In this particular case study we use the apamarga kshara tail oil for the uttarbasti procedure in the patient having history of recurrent urethral stricture. Patient also underwent urethroplasty twice. The results found in the case are encouraging enough. The study was completed in North eastern Institute of Ayurveda And Homoeopathy, Ayurveda hospital Shillong.

        Special Issue Article Pages: 6 - 7

        Polycystic Ovarian Syndrome: The mother of all lifestyle disorders in women - An Ayurvedic approach to its management

        Monika Chauhan

        PCOS is probably fastest growing health hazard amongst women of reproductive age. The prevalence of this disease in general population is about 5-10% world-wide. This familial disorder appears to be inherited as a complex genetic trait.The association of amenorrhoea with bilateral polycystic ovaries and obesity was first described by Stein & Leventhal. It is characterized by a combination of hyperandrogenism (clinical or biochemical), chronic anovulation and polycystic ovaries. This is frequently associated with insulin resistance and obesity. This condition is receiving so much attention due to its high prevalence and possible reproductive, metabolic, and cardiovascular consequences. It is the most common cause of hyperandrogenism, hirsutism, and anovulatory infertility in developed countries.As the aetiology is poorly understood, there is controversy about diagnostic criteria, clinical features of the syndrome. The management of PCOS is difficult and challenging task, faced by modern gynaecologists. So the holistic approach is demanded specially in Indian subcontinent because of high prevalence here (52%). This particular feminine disorder is not described word to word in Ayurveda. PCOS associated some features are closely related with some of Yonivyapada yet some features nearly bring into its relation with Aartvadushti. Word Aartava has been used extensively in Samhita in context of menstrual blood, ovum and ovarian hormones. Ayurveda, the age-old science of life, speaks of prevention and cure of PCOS through Aahar (Diet), Vihaar (Lifestyle Modification) and Aushadh (Medicine). Possible line of treatment is stipulated with Nidanaparivarjan, Samshodhana, Aaganeya Dravya, Savayonivardhana Dravya.

        Complementary Medicine and Pharmacoeconomics (2021)

          Special Issue Article Pages: 1 - 1

          Evaluation of health care delivery, safety procedures, and canine welfare in an inpatient Animal-Assisted Therapy (AAT) program: A multicenter Failure Modes and Effects Analysis (FMEA)

          Christian Tejeda*, Jeannette Meyer, Erin Rice, Kunal Wahi, Jennifer Dobkin, Dr. Megan Trieu, Dr. Daniel Karlin

          Background: Growing evidence supports the use of animal-assisted therapy (AAT) as complementary therapy for various clinical conditions. In the academic literature, increasing evidence highlights utilization of AAT to address pain, anxiety, stress, depression, enhance mood, increase socialization, and increase energy levels. Currently, there is limited evidence-based practice research identifying and addressing areas of improvement within AAT programs. Our research aims to evaluate AAT at our institution using a Failure Modes and Effects Analysis (FMEA).
          Methods: An FMEA is a tool for conducting a systematic analysis of a process in which potential risks may occur. For our study, we formed a multidisciplinary team and convened for 6 sessions to complete an FMEA table. Our research team reviewed, evaluated, and recorded failure modes pertaining to three process categories: health care delivery, safety procedures, and canine welfare. We devised improvements to prevent the identified failure modes.
          Results: The process tree created consists of 8 subprocesses and 40 total steps or entries. The data analysis indicated 16 total failure modes, with RPNs ranging from 2 to 48 among which 4 failure modes fell within the “very high” risk category with RPNs greater than 40. The data analysis indicated that the two failure modes with the highest RPNs included failure to complete request list (RPN: 48) and canine contamination of injection site(s) (RPN: 48).
          Discussion: For half of 16 failure modes, we found improving the program’s orientation and training process to be an appropriate preventative action. We will continue conducting evaluations of every failure mode at 3, 6, and 12-month time points. These results bear importance to a better understanding of the current challenges and improvement opportunities for inpatient AAT. One limitation of the study was the relatively small size of the research team which could have included more agents within the overall process.

          Special Issue Article Pages: 2 - 2

          Evaluation of Pistacia vera L. efficacy (Syrian traditional medicine) as adjuvant treatment for Cutaneous Leishmaniasis

          Chadi Khatib

          Our search has mainly focused on the use of the traditional dermal cream that consists of an extract of pistachio fruit peels and its tree gum as adjuvant treatment of Cutaneous Leishmaniasis. Pistacia vera L. is a plant of Syrian origin, and the oldest tree of this plant exists in Al-Qalamoun area in Rural Damascus in Syria. As the peels of Pistacia vera L. fruits and the gum of its tree are rich with the phenolic substances. Cutaneous Leishmaniasis is seen in more than 80 countries all over the world and the Mediterranean region is considered one of the most affected areas with this epidemic, knowing that Aleppo is historically considered the home for this disease and that's why, this disease is called "Aleppo Boil", the spread of this epidemic has markedly increased in the world. There is no vaccine for Leishmaniasis and the available chemical treatment, that includes several ant parasites such as the Pentium-equivalent antimony derivatives including antimoniate meglumene and sodium stibogluconate has several limitations including among others, its variable efficacy depending on the type of parasite and the potential resistance for it, its high toxicity for the liver and heart, the long treatment duration and its high cost. Due to the above-mentioned facts, the drugs co-treatments (chemical-chemical) is getting more consideration. Besides, the natural products have recently become an unlimited source for developing anti Leishmania drugs given that they provide better level of efficacy and safety along with lower levels of toxicity in addition to their lower cost. We have assessed the efficacy of the ethanolic extracts of Pistacia vera as anti-Leishmaniasis in both in vitro and clinical study through topical administration.
          The in-vitro tests were conducted using the ethanolic extracts of Pistacia vera tree's gum and the L.tropica parasites viability. The results showed a good biological effect when treating the parasites with gradually increased concentrations of the ethanolic extracts during the 48 hours of incubation. The double- blinded clinical study was conducted on 102 patients at the Leishmania center in Aleppo. The clinical results and observations showed that the local complementary treatment with the extracts of both the skin peels of Pistacia vera L. fruits and the gum of Pistacia vera L. tree could support the chemical treatment with antimoniate meglumene (administered through local injection) in treating the Cutaneous Leishmaniasis. The above mentioned support is manifested with reducing the injured area and its hardness in addition to reducing the edema and the redness. Besides, the above mentioned extracts could significantly support the treatment of the secondary infection and its associated ulcer.

          Special Issue Article Pages: 3 - 3

          Rediscovering herbal contraceptives in Ayurveda - Windows of research via ethnopharmacological research

          Charu Sharma *, Sujata Kadam, Meenakshi Pandey

          In the time you read the title , there would have been 4 live-births around the globe. 210 million pregnancies occur worldwide each year, of which, 40% are un palnned. Current researches are centred around immunocontraceptives, molecular condoms but there is an immense quest for completely safe and used friendly contraceptive. Ethnopharmacological-Driven Drug Development becomes the need of the hour to establish noble solutions for global concerns. This review article is a methodology to analyze the pharmacological aspect of contraceptives along with evaluating the current scenario of researches in the drug development process of contraceptives. This article summarizes the results of various classical references and researches related to drug discoveries of contraceptives. This artcle deals with future leads to herbal contraceptives and presents an interdisciplinary model of research.

          Special Issue Article Pages: 4 - 4

          Holistic interventions in Ayurveda for a healthy progeny

          Charu Sharma

          Prenatal care is known as “garbhini paricharya” in Ayurveda. ‘Garbhini’ means pregnant woman and ‘paricharya’ means ideal protocol. It includes the ideal dietary and lifestyle protocol followed by a pregnant woman to attain optimum health of progeny and prevent any complications. The guidelines for prenatal care start even before conception. The couple planning to have a progeny shall follow purification procedures (panchakarma), proper diet and life style modifications as part of preconception care. The prenatal care begins from the very first day when the woman expects the conception (usually due to missed menstrual cycle). The conceived woman shall be treated with special care just like a pot filled with oil. As the slightest oscillation of such a pot causes spilling of the oil, similarly the slightest exertions or excitements to the pregnant woman can initiate adverse pregnancy outcomes.

          Special Issue Article Pages: 5 - 5

          Natural Anamorphosis Process

          Alexandros Senarelis-Sinaris

          With the deepest respect to the human imperfect, Natural Anamorphosis Process operates non-aggressively towards the cryptoalgorithm of any form of problem and the noisy, foggy, obfuscating dynamics of its potential complications. With the physio-logical tactic of its centrifugal approach, moves peripherally and in between (neutral behavior) the event horizons of the healthy bio-available and any pathology, disease, illness, syndrome, injury etc, which is basically the "abstract" area of the emerging stress before the true values-1 (biophotons-light-energy-electricity-3D holographic & elctromagnetic fields) inevitably become false values-0 (nihilism). With the introduction and the usage of valuable and complex information (informational medicine) of undoubtedly rigorous sciences such as mathematics, physics, biology and philosophy, NAP as a regulator/buffer aims for the least action path (Hamilltonian physics) and with the controlled repetition (enrgams) of its intentional systems & agents, intends to maintain and enhance the physio-logical mechanisms of homeostasis and, by extension, through the parasympathetic system (vagus nerve-interoception) the stored energy levels of healthy bioavailability, since they form the absolute natural intrinsic self repair mechanism of smoothness and existence (Navier-Stokes). NAP is an innocuous Salutogenic (health-stress-coping) neuro-based independent Naturopathic system with neutral behavior. Neuronal stimulation (e.g transdermal, transensory) is an emerging field in modern medicine. As neuronal networks were evolutionarily selected to achieve physiological homeostasis, it is not surprising that neuromodulation emerged as one of the first strategies used in medicine to reestablish homeostasis during illness. Scientific studies indicate that the design of novel non-invasive techniques for nerve stimulation can help control immune and organ functions. NAP is based purely on the logic behind the mathematical symmetric property of equality, by creating simple models of complex bio-logical neuro-behavioral organic algorithms (simplexity). So when therapy by definition aims to normalize a distorted biological condition, actually what it does is to try to bring biochemical regularity (normal functioning). Now if we see it from another perspective (Anamorphosis), by intensifying or enduring the normal bio-available functioning (eurythmia), essentially we are in a therapeutic sphere of influence via a simple reverse process thinking mechanism (logic).

          Volume 6, Issue 1 (2021)

            Research Article Pages: 1 - 3

            When do Rayleigh and Weibull parametric models predict the same results? A short note

            Martin Connock, Mubarak Patel, Daniel Gallacher and Aileen Clarke

            Health Technology Appraisals (HTA) model survival data using a conventional set of six parametric distributions. Alternative and potentially useful distributions
            exist and could also be exploited.
            Rayleigh 2 parameter (R2P) and Weibull models are both defined with two parameters and exhibit monotonic hazard; the Rayleigh model is relatively unused in
            HTA and should not be regarded as just a special case of the Weibull model.
            Aim: To explore circumstances where the predictions from R2P and Weibull models may differ or coincide.
            Method: Stata software was used to model sample survival data with R2P and Weibull models and to compare the predicted hazard and survival from each
            parametric.
            Results: R2P models generate different predictions to Weibull models except in the special case where the Weibull shape parameter equals or closely approaches
            two and the Weibull hazard prediction is linearly increasing. When compared to Weibull models R2P models may generate a better fit to observed data according
            to conventionally used indicators of goodness of fit.
            Conclusion: Rayleigh modelling of survival warrants inclusion in the survival modelling undertaken in Health Technology Appraisals.

            Volume 5, Issue 1 (2015)

              Research Pages: 298 - 304

              ANTIHYPERLIPIDEMIC ACTIVITY OF CAMELLIA SINENSIS AND MACROTYLOMA UNIFLORUM ON HIGH FAT DIET INDUCED WISTAR ALBINO RATS

              Dhanalaxmi Mohan Raj*, K. Bhaskar Reddy

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              Hyperlipidemia is a disorder of lipid metabolism manifested by elevation of plasma concentrations of the various lipid and lipoprotein fractions, which is the key risk factor for cardiovascular disorders (CVD). Camellia sinensis and Macrotyloma uniflorum used as antihyperlipidemic drugs as per literature review. The aim of the present study was to evaluate the antihyperlipidaemic activity of polyherbal formulation of methanolic extract (Camellia sinensis and Macrotyloma uniflorum) in High fat diet (HFD) fed rats. Male Wistar albino rats were randomly assigned to five groups: Groups I normal control; Group II HFD control; Group III HFD+ standard drug (Atorvastatin10 mg/kg), Group IV HFD + Polyherbal methanolic extract (200 mg/kg) and Group V HFD + Polyherbal methanolic extract (400 mg/kg). The whole study lasted for 28 days. Administration of HFD caused a significant (p<0.05) rise in the serum total cholesterol (T.C), LDL-cholesterol, VLDL-cholesterol, triglycerides (T.G). Simultaneous administration of polyherbal methanolic extract of Camellia sinensis and Macrotyloma uniflorum significantly (p<0.05) prevented the rise in serum total cholesterol, LDL-cholesterol, VLDL-cholesterol, triglycerides. There was a significant decrease in body weight and increase in HDL-cholestrol was observed in polyherbal extract treated rats. Thus, the results indicate antihyperlipidaemic effect of Polyherbal formulation.

              Natural Products and Pharmacoeconomics-1 (2021)

                Special Issue Article Pages: 1 - 1

                Novel PPAR? antagonists bearing Stilbene or Bioisosteres endowed with antiproliferative effects in cancer cell lines

                Alessandra Ammazzalorso

                Peroxisome Proliferator-Activated Receptors (PPARs) have been widely studied in the last decades, and they attracted the attention of scientists as promising therapeutic
                targets. Intensive efforts by researchers produced a wide panel of drugs targeting the three PPAR subtypes (PPARα PPARγ PPARδ) able to modulate important metabolic
                functions. PPAR activation is involved in several physiologic pathways, as lipid and glucose metabolism, insulin sensitivity, energy homeostasis, and cell differentiation.
                Fibrates and thiazolidinediones, respectively synthetic PPARα and PPARγ agonists, are currently used for the treatment of hyperlipidemia and hyperglycemia, in patients
                affected by type 2 diabetes and metabolic syndrome.
                In recent years, an increased expression of PPARα has been found in different tumors: it is well known that cancer cells present altered metabolic pathways, switching from
                the glycolysis to fatty acid oxidation metabolism. In this scenario, PPARα antagonists emerged as novel potential drugs in tumors overexpressing PPARα by interfering
                with cellular survival and metastasis formation.[2] In vitro anticancer effects were found for PPARα antagonists in chronic lymphocytic leukemia [3], renal cancer, colorectal
                and pancreatic cancer [4], paraganglioma [5].
                In this study we report on the synthesis of novel PPARα antagonists bearing stilbene or its bioisosteres, starting from the structure of a dual PPARα/γ agonist, previously
                synthesized in our laboratory. We explored the cytotoxicity of the novel compounds in different cancer cell lines (colorectal, pancreatic, renal, paraganglioma) expressing PPARα.

                Special Issue Article Pages: 2 - 2

                Thymoquinone attenuates phosphorylation of AKT to inhibit kidney cancer cell proliferation

                Ayed Dera *, Prasanna Rajagopalan

                Background: Nigella sativa is extensively used for medical remedies since ages in Middle East. Thymoquinone (Tq) is the major active constituent of this plant in which many reports confirmed the anticancer activities of the compound. However, the effect of Tq in kidney cancer cells and the pathway of action remains unproven. Herein we report anticancer properties of Tq in the kidney cancer cells. Methods: Cancer proliferation was assessed using A498 and Caki1 kidney cancer cells 000by MTT assay. Nuclear fragmentation was detected using Hoechst 333258 and Propedium iodide dual straining. Trans endothelial migration assay was used to study migration inhibitory effects of Tq. Flow cytometry was used to analyze apoptosis and cell cycle. Anti, pro apoptotic markers and Akt phosphorylation were measured by Western bolting procedure. Results: Tq demonstrated anti-proliferative effects in A498 cells with GI50 value of 40.07 μM and Caki-1 cells with GI50 of 51.04 μM. Tq exhibited nuclear fragmentation and inhibited trans-endothelial migration of A498 and Caki-1 cells in a dose dependent manner. Time dependent increase of Annexin V positive cells and sub G0/G1 cell population was observed in both cell lines after Tq treatment. Tq increased the pro apoptotic Bax protein and reduced anti-apoptotic Bcl-2 protein dose dependently in A498 and Caki-1 cells favoring apoptosis. Increasing concentration of Tq decreased the phosphorylation of Akt in both kidney cell types. Conclusion: Our observations suggest effective anticancer activity of Tq in kidney cancer cells which may be mediated by the Akt pathway.

                Special Issue Article Pages: 3 - 3

                Use of antioxidants from Brazilian Cerrado plants on veterinary medicine

                Melo, FR *, Cruz-Junior, CA, Fidelis, AAG

                Statement of the Problem: Several animal diseases involve an increase on reactive oxygen species (ROS) production, which could cause biological effects as aggravating of preexisting
                diseases or cell damage in infectious diseases. In addition, in vitro embryo production (IVP) induces excessive ROS production, which affects blastocyst quality. Therefore,
                the use of antioxidants represents an alternative to overcome oxidative stress damage both, in infectious diseases and in improving animal reproduction procedures. Brazil is a
                country of interest to ethnopharmacology, especially the ecological domain Cerrado, which represents a source of biological diversity. The purpose of this study is to evaluate crude
                extracts of plants from Cerrado used in traditional medicine, for the presence of phenolic compounds as well as its antioxidant activity, antibacterial and effect on apoptosis in IVP.
                Methodology & Theoretical Orientation: the crude extracts were obtained from several plants selected due to its traditional use. Leaves were dried, powdered and exhaustively
                extracted by maceration. The crude extracts were used do determinate in vitro phenolic compounds, antioxidant activity, antimicrobial activity, and apoptosis proportion on IVP.
                Findings: All plants studied showed expressive antioxidant activity, and the phenolic compounds amounts were different for each other. Those that showed majority
                antioxidant activity were used in antibacterial activity and in IVP tests. The crude extract of cagaita (Eugenia dysenterica Mart. DC.) showed antimicrobial activity against
                Staphylococcus intermedius, an important bacterium that causes infection in dogs and cats. The same extract also showed a significant reduction (p<0.05) in the proportion
                of apoptotic cells from embryos cultivated with 0.01 mg/mL.
                Conclusion & Significance: Antioxidative activity of natural products, especially those extracted from medicinal plants, is extremally important to provide scientific data for
                the treatment of infectious disease or in procedures of IVP. These extracts, normally, cause low side effects and can take advantage of complementary veterinary medicine

                Special Issue Article Pages: 4 - 4

                Revisting the use of Rubefacient in reducing the blood sugar level of people with type II diabetes via Clinical Aromatherapy

                Fai Chan

                acceptance among the medical professionals. The word “Rubefacient” stems from the use of the drug to“produce redness of the skin, e.g. by causing dilation of the
                capillaries and an increase in blood circulation. “ According to Wikipedia definition and there are some topical drugs that can achieve it. In fact , the TCM (Traditional Chinese
                Medicine) uses of the technique “Gua Sha” can achieve rubefacient effect too.
                The speech will discuss this technique combining with the use of essential oil massage in treating type II diabetes and how this integrative approach brings down the blood
                sugar levels to a significant extent that complement well with the conventional drugs in treating the diabetes. Actually, the author made use of this to help one diabetic person
                to reverse her diabetes and two of them to significant drops of blood sugar level and resolved the severe insomnia issue…
                Except for the mechanical technique of “Gua Sha” , essential oil blend that can create “rubefacient” effect is also employed… The formulation and its therapeutic applications
                will also be discussed. Last but not least, not each part of the whole body deserves the same attention. There will be discussion on which should go first as this will affect
                the result, specially when time is limited. This presentation not only tells you the facts or evidence but also points to the way that you can improve your formulation to better
                serve your customers.

                Special Issue Article Pages: 5 - 4

                Supercritical CO2 technologies: A GREEN alternative with applications in natural products (HEMP) isolation and characterization

                Gerard Rosse

                Supercritical fluid technologies for CO2 purification (SFC) and CO2 Extraction (SFE) are efficient and cost-effective to produce intact extracts and high purity ingredients relevant to
                Hemp, Flavors and Fragrances, Herbal Medicines, Spices, Decaffeination, Sterilization, Nutraceuticals & Aroma Therapy, Algae Extraction and Pharma industries. The seminar
                covers fundamentals and latest applications of SFC and SFE in analysis and purification of chiral/achiral small molecules, peptides and complex extracts relevant to the Pharma,
                Hemp and other Natural Products industries. CO2 extraction is a non-flammable, non-toxic process enabling isolation of volatile/non-volatile compounds and leaving no trace
                of toxic residual solvent. CO2 purification is a form of liquid chromatography that happens to use CO2 as a solvent to facilitating fast analysis and separation of complex mixtures.
                Both SFE and SFC use reclaimed carbon dioxide and automatically recycle it, contributing further to sustainability, high efficiency, low operating costs and increased profitability.

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