Ethnobotanical uses of wild flora and fungi on the circum-Sicilian island of ...Cassandra Quave
This is a presentation given at the 2015 meeting of the Society for Economic Botany.
Abstract:
In 1969, Galt and Galt conducted an ethnobotanical survey [1] in the community of Khamma on the circum-Sicilian volcanic island of Pantelleria, located 67 km from the Tunisian coast. Since then, a number of botanical studies concerning the local wild flora and cultivation of the zibebo grape and capers have been conducted, but none have investigated traditional ecological knowledge regarding the use of wild plants and fungi. Here, 45 years later, we revisit this topic, examining the current day knowledge and practices concerning wild plants and fungi on the island. A total of 42 in-depth interviews were conducted in June 2014 in six communities. All interviews were conducted in person in Italian with prior informed consent. We employed two primary means of eliciting responses concerning traditional practices; informants were asked to: 1) free-list the most commonly used plants for wild foods, general medicine, and skin remedies; and 2) view and discuss a booklet composed of photos of taxa listed in the Galt study.
A total of 86 botanical and 19 fungal taxa representing 54 families were cited by the study participants. While many plant-based traditions have disappeared from daily practice, especially those related to traditional fishing and hunting, they remain in the memories of the eldest subset of the population. For example, one of the most pervasive species in the landscape, Opuntia ficus-indica, has current day uses that persist (e.g., food source and shade source for cultivated vegetables), but its past applications were much more diverse, and included manipulation into hunting snares for birds. Other predominant flora included a number of Euphorbia spp., whose toxic latex was regularly used as a fish poison. Fungi, on the other hand, represent an important source of wild food today, and are widely recognized and regularly consumed. In conclusion, we have found that traditional e knowledge remains important to everyday practices of Pantescans, ranging in applications from wild foods, agricultural tools, and traditional medicines.
Atlanta Botanical Garden Science Cafe: Medicines from Nature - 2014Cassandra Quave
In 2014, Dr. Quave presented a Science Cafe talk at Atlanta Botanical Gardens: "Medicines From Nature: Adventures of a Medical Ethnobotanist"
Abstract:
Ethnobotany is the study of human interactions with plants. It has perhaps been best defined as the science of survival as it involves the study of plants used in our daily lives for food, medicine, shelter, art, and much more. In this science café, Dr. Quave will discuss her research on medicinal plants for the treatment of infectious disease. From remote regions of the Amazon to volcanic islands in the Mediterranean and isolated mountains in the Balkans, Quave has conducted fieldwork in some of the most biologically diverse regions of the planet. She will share some of her adventures as a medical ethnobotanist and explain how traditional knowledge may be the key to the discovery of new life-saving medicines.
Pesticide Induced Resurgence of Rice Planthoppers
major resurgence species are as follows:
BPH- Nilaparvata lugens Stal
WBPH- Sogatella furcifera Horvath
SBPH- Laodelphax striatellus Fallen
Introduction
Type and Form of Resurgence
Population Characteristics of Planthopper Resurgence
Resurgence Factors of planthoppers
Planthoppers reproduction associated factors
Hormoligosis
Pesticides influence male accessory gland protein
Conclusion
Prospective Research Direction
Ethnobotanical uses of wild flora and fungi on the circum-Sicilian island of ...Cassandra Quave
This is a presentation given at the 2015 meeting of the Society for Economic Botany.
Abstract:
In 1969, Galt and Galt conducted an ethnobotanical survey [1] in the community of Khamma on the circum-Sicilian volcanic island of Pantelleria, located 67 km from the Tunisian coast. Since then, a number of botanical studies concerning the local wild flora and cultivation of the zibebo grape and capers have been conducted, but none have investigated traditional ecological knowledge regarding the use of wild plants and fungi. Here, 45 years later, we revisit this topic, examining the current day knowledge and practices concerning wild plants and fungi on the island. A total of 42 in-depth interviews were conducted in June 2014 in six communities. All interviews were conducted in person in Italian with prior informed consent. We employed two primary means of eliciting responses concerning traditional practices; informants were asked to: 1) free-list the most commonly used plants for wild foods, general medicine, and skin remedies; and 2) view and discuss a booklet composed of photos of taxa listed in the Galt study.
A total of 86 botanical and 19 fungal taxa representing 54 families were cited by the study participants. While many plant-based traditions have disappeared from daily practice, especially those related to traditional fishing and hunting, they remain in the memories of the eldest subset of the population. For example, one of the most pervasive species in the landscape, Opuntia ficus-indica, has current day uses that persist (e.g., food source and shade source for cultivated vegetables), but its past applications were much more diverse, and included manipulation into hunting snares for birds. Other predominant flora included a number of Euphorbia spp., whose toxic latex was regularly used as a fish poison. Fungi, on the other hand, represent an important source of wild food today, and are widely recognized and regularly consumed. In conclusion, we have found that traditional e knowledge remains important to everyday practices of Pantescans, ranging in applications from wild foods, agricultural tools, and traditional medicines.
Atlanta Botanical Garden Science Cafe: Medicines from Nature - 2014Cassandra Quave
In 2014, Dr. Quave presented a Science Cafe talk at Atlanta Botanical Gardens: "Medicines From Nature: Adventures of a Medical Ethnobotanist"
Abstract:
Ethnobotany is the study of human interactions with plants. It has perhaps been best defined as the science of survival as it involves the study of plants used in our daily lives for food, medicine, shelter, art, and much more. In this science café, Dr. Quave will discuss her research on medicinal plants for the treatment of infectious disease. From remote regions of the Amazon to volcanic islands in the Mediterranean and isolated mountains in the Balkans, Quave has conducted fieldwork in some of the most biologically diverse regions of the planet. She will share some of her adventures as a medical ethnobotanist and explain how traditional knowledge may be the key to the discovery of new life-saving medicines.
Pesticide Induced Resurgence of Rice Planthoppers
major resurgence species are as follows:
BPH- Nilaparvata lugens Stal
WBPH- Sogatella furcifera Horvath
SBPH- Laodelphax striatellus Fallen
Introduction
Type and Form of Resurgence
Population Characteristics of Planthopper Resurgence
Resurgence Factors of planthoppers
Planthoppers reproduction associated factors
Hormoligosis
Pesticides influence male accessory gland protein
Conclusion
Prospective Research Direction
Multi Drug Resistant Bacteria.
multidrug resistance is a condition enabling a disease causing organism to resist distinct drug or chemical of a wide variety of structure & function targeted at eradicating the organism
Host-pathogen Interactions, Molecular Basis and Host Defense: Pathogen Detect...QIAGEN
Host–pathogen interactions are strikingly complex during infection. This slidedeck provides an overview of the molecular basis of these intricate interactions: the impact of microbiota on innate and adaptive immunity, metabolism, and insulin resistance and host defense mechanisms. Various research tools will be introduced to simplify and streamline each step of studying the host response, enabling detection of pathogens, analysis of gene expression and regulation, epigenetic modification, genotyping and signal transduction pathway activation.
phage therapy is the use of bacteriophages to kill pathogenic bacterial cells. Bacteriophages are bacterial parasites that invade bacterial cells and engulf them like blue whale fish kills euphausiids and copepodsand in sea .
Multi Drug Resistant Bacteria.
multidrug resistance is a condition enabling a disease causing organism to resist distinct drug or chemical of a wide variety of structure & function targeted at eradicating the organism
Host-pathogen Interactions, Molecular Basis and Host Defense: Pathogen Detect...QIAGEN
Host–pathogen interactions are strikingly complex during infection. This slidedeck provides an overview of the molecular basis of these intricate interactions: the impact of microbiota on innate and adaptive immunity, metabolism, and insulin resistance and host defense mechanisms. Various research tools will be introduced to simplify and streamline each step of studying the host response, enabling detection of pathogens, analysis of gene expression and regulation, epigenetic modification, genotyping and signal transduction pathway activation.
phage therapy is the use of bacteriophages to kill pathogenic bacterial cells. Bacteriophages are bacterial parasites that invade bacterial cells and engulf them like blue whale fish kills euphausiids and copepodsand in sea .
The inhibitory activity of L. crispatus against uropathogenes in vitroIJMCERJournal
ABSTRACT: Bacterial interference refers to the use of bacteria of virulence to compete with and protect against
colonization and infection by disease causing organisms. In this study, L. crispatus strain was used to detect its
antibacterial activity towered five species (one Gram-positive and four Gram-negative ) of the most common bacteria
causing urinary tract infection. L. crispatus completely inhibited growth of Staphylococcus aureus , while it had no
inhibitory effect on three of the other species.
Key Words: inhibitory activity, L. crispatus, uropathogens
Literature Survey Antibiotic ResistanceTuhin Samanta
Anti-toxin obstruction happens when microscopic organisms change in light of the utilization of these medications. Microscopic organisms, not people or creatures, become anti-toxin safe. These microorganisms may contaminate people and creatures, and the diseases they cause are more diligently to treat than those brought about by non-safe microscopic organisms.
Nowadays, there is a demand for novel
drugs to prevent these infections and the emergence
from mutation of microorganisms. Given the rising
incidence of resistance to synthetic antibiotics and in
light of the rising costs of medicines it is well-timed
to search for natural products such as plant derived
antimicrobial drugs to reduce the resistance of
microorganisms. Pandan (Pandanus amaryllifolius),
in addition to synthetic alternatives, has the potential
of antibacterial activity. The antibacterial properties of
established. For that reason, the research proponents
of this study aims to assess the antibacterial properties
of pandan with the end view of providing low cost
of medications and the prevention of resistance. This research analyzed the in vitro activity of pandan
leaves crude extract against bacterial isolates such as
Staphylococcus aureus
ATCC 25923, Escherichia coli
ATCC 25922 and
Pseudomonas aeruginosa
ATCC 27853.
About 1 kilogram of freshly collected pandan leaves
was subjected to water distillation and the filtrate
was concentrated using rotary evaporator. The crude
extract was then used for the phytochemical analysis.
The Minimum Inhibitory Concentration (MIC) and
Minimum Bactericidal Concentration (MBC) of pandan
against the said microorganisms were examined. This
study also determined the stability of pandan as to pH
and temperature.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS
project mutamba
1. THE EFFICIENCY OF THE TANINN EXTRACTED FROM THE
Guazuma ulmifolia IN THE REVERSE TRANSCRIPTASE INHIBITION
OF THE HIV VIRUS
PAULO ANTONIO RODRIGUES GOUVEIA
2. 1. INITIAL CONSIDERATIONS
Virus is the smallest particle that exists; it only can be seen by the
microscope. The virus, so that it can live and multiply itself, needs to be inside of the
cells of an organism where it can assume the command, making them work to it
(Adesokan et al, 2004).
The AIDS/SIDA “Acquired Immunodeficiency Syndrome” is caused by HIV,
a virus that, firstly, attacks the immune system; then, it can install itself in several
parts of the body. When the virus affects the immune system, its action becomes
inefficient and the body becomes more vulnerable to any disease that may occur
(Barre-Sinoussi et al., 1983; Brown, 2000).
The HIV is a retrovirus, which means that its genetic material is in RNA
shape instead of DNA shape, and to replicate itself it must, firstly, create a DNA copy
from its genetic material (Buckheit Jr et al., 2001).
The HIV virion has a complex structure and it is grossly spherical, with a
diameter of approximately 1/10.000 mm. The virus external coverage is a double
layer of lipidic molecules sprinkled with proteins (the envelope proteins, gp120 and
gp41). Inside of it, a layer of protein matrix surrounds the conical capsid, or nucleus,
that contains the RNA of the HIV (Brown, 2000).
A cell infection occurs when the HIV virion connects itself to a cellular
receptor, generally the CD4, through its protein gp120; then, the virus merges itself to
the cellular membrane and the content of the capsid is liberated in the cellular
cytoplasm. The HIV enzyme, the reverse transcriptase, catalyses the production of a
DNA copy of the RNA from the HIV and the component ribonuclease-H from the
reverse transcriptase, finally, removes the RNA helix, now redundant. The DNA copy
of single helix is, then, converted by the reverse transcriptase into a DNA copy of
double helix, which is transported to the cellular nucleus where a second HIV
enzyme, the integrase, catalyses the incorporation of the viral DNA to the host
genetic material (Adesokan, 2004).
3. The antiretroviral therapy is aimed to the prevention of the viral replication,
with different drugs addressed to various stages of the replication cycle. The
antiretroviral drugs currently available to treat the HIV infection are a series of
inhibitors of the reverse transcriptase, that act previously to the incorporation of the
viral genetic material to the host chromosome and the inhibitors of the protease,
which act subsequently to this step and prevent the virion formation with functional
proteins, that is, of infectious virus. The cocktail is an association of the two kinds of
medicines.(Chi et al., 2004).
The reverse transcriptase inhibitors prevent the virus transforming its
genetic code from ARN into ADN, a required operation to multiply itself inside the
cells (Costi et al, 2004).
Several natural compounds are being studied about the retroviral inhibition
of the HIV reverse transcriptase; among them are the taninns, which are phenolic
compounds characterized by their capacity of combining themselves with proteins
and other polymers, such as polysaccharides (Buolamwini e Assefa, 2002).
Studies have shown that the bark and the bast of the Guazuma ulmifolia
(mutamba) are rich in components with pharmacologic properties. It presents
triterpenes, alkaloids and reasonable amount of tannins (Costi et al., 2004).
The tannin properties are linked to its capacity of forming complexes with
the proteins that participate of the tissues in relation to the microbiological attacks.
Besides, they confer taste properties united under the term astringency, have antifree radical power and have the capacity of consuming dissolved oxygen, that is,
they have interesting antioxidant properties to the pharmacologic function and also
show powerful activity against the HIV replication (Cocuzza, 2001).
4. 1.1 GUIDING QUESTIONS
Does the tannin extracted from the Guazuma ulmifolia show the best inhibitors
pharmacokinetic profiles of the HIV reverse transcriptase with fewer sideeffects?
Which molecular weight of the tannin has the retroviral inhibitor action of the
HIV reverse transcriptase with fewer toxicity?
1.2 OBJECTIVES
General:
To identify the efficiency of the Guazuma ulmifolia plant substracted as a viral
duplication inhibitor of the HIV reverse transcriptase with a lower toxicity risk.
Specific:
To identify the tannin molecular weight that has retroviral inhibitor action of the
HIV reverse transcriptase with lower toxicity risk.
To promote the reduction of the viral load preservating the function of the
immunologic system.
To postpone the illness evolution changing the HIV natural history.
5. 1.3 JUSTIFICATIVE
Although the therapy appearance, which reduces the viral particles to
undetectable levels, the virus persists in reservoirs in the organism, as T sleepy
lymphocytes. The emergence and the appearance velocity of resistant strains to
different medicine combinations available in the market also is a limitant factor. But
one of the factors that makes the anti-HIV therapy more difficult is the high incidence
of side-effects caused by the medicines currently available. Searches realized by
Ligani Jr. and partners showed to be this one the main cause of faults in the
antiretroviral therapy adherence (20,5%), characterized mainly by vomits, diarrhea,
nauseas and abdominal pain, beyond headaches and, even so, changes in skin
color.
Despite several laboratories and search groups are working in the HIV
inhibitors development, no compound has arisen that can be effectively used in the
therapeutic.
This foment a great need of discovery and/or development of efficient
drugs that act on the reverse transcriptase (RT), on the protease (PR) and on other
points of the viral replication cycle. Then the great challenge is to find possible
targets that effectively interrupt the virus cycle, without harming the normal cell
(Dayam, 2003).
The use of herbal medicines is the result of the secular accumulation of
empirical knowledge about the herbal action by different ethnic groups. However,
there are questions about the standardization of production techniques and herbal
medicines marketing (De Clercq, 2000).
Some studies have treated about the antinutritional aspect of cultivars with
high levels of tannins and the resistance to pests and seasonality has been
considered as an interesting factor to some species (De Clercq, 2002).
It’s found, in the vegetables, relatively important amounts of phenolic
compounds. Their role is essentially to protect the issues against the attacks of
insects, fungi or bacteria. It’s considered a passive defense system relatively
6. efficient. The plants also can produce great amounts of phenols based in an
alteration in the live cells surface: it’s the active defense. The best example is given
by the bite from insects in the leaves that are the source of the galls formation.
A mutamba tree had been observed for ten years and it was realized that
in certain period of the year it was notorious the presence of dry galls nearly reaching
70% of length and as the days went by, the plant recovered itself showing resistance
to the pest that had affected it.
In 1946, in Faina – GO, the researcher Francisco Cabral de Melo, a
pharmacist graduated from UFRJ, and partners realized some tests, undocumented,
in patients with yellow fever using the mutamba tannin that has a low molecular
weight, having favorable outcome, there was a cure in 100% of the cases, with no
toxicity demonstration.
Tannin molecules are being tested with the intention of discovering an
efficient drug against HIV. Kilkuskie and partners had observed that galotannins
showed inhibitory activity only in toxic concentrations, elagitannins and condensed
tannins poorly inhibited the viral replication and the complex tannins showed powerful
activity against the HIV replication.
It justifies the great importance of a survey with tannins of low molecular
weight and smaller toxicity.
So, the interest in the survey begins because there is no cellular
equivalent, what is an advantage in relation to smaller chances of occurring sideeffects, and it has a social and scientific relevance because there is no endogenous
mediator which chemical structure can be used as a prototype.
7. 2. THEORETICAL FUNDAMENTS
The viruses are involved in a big variety of chronic and degenerative
diseases, being responsible for more than 60% of the human diseases
(Korolkovas,1988). The fight against viral infections is hard, because the viral
replication is an intracellular process, being closely related to the metabolism of the
infected cells (Barre-Sinoussi, 1983). One of the most studied virus nowadays is
named “Human Immunodeficiency Vírus” (HIV), from retrovirus family (ANR
compound); it is able to be parasitic upon man’s immune system, leading to an
infectious disease known as “Acquired Immuno Deficiency Syndrome” (AIDS)
(Johnson, 1989).
HIV is different from the other viruses because it attacks and damages the
immune system, that is its main target in the human organism. One of the
components of the immune system are the T lymphocytes, that attack directly the
invader microorganism. Among the T lymphocytes there is a class called T4 (CD4+ T
or T-helpers), which has a very important role in the initiating of an immune response
and in the coordination of the same response, being the HIV main target (Gupta,
1979). This virus, when infecting the CD4+ T, lead to the lack of coordination of the
immune system and to its gradual in effectiveness, establishing an immunodeficiency
(De Clercq, 2000).
In Brazil, from 1980 to December 2002, 257.771 cases of the disease
were reported, with 113.840 known deaths. Throughout serological tests conducted
by the Brazilian Department of Health, at least 536.000 Brazilians are expected to be
infected with HIV (Souza, 2003).
It’s worth highlighting three big stages in the epidemic’s evolution: 1 – an
initial stage, characterized by the infection among men that have sexual relations
with other men, and by a patient’s high level of education; 2 – a second stage,
characterized by an increase of cases due to the transmission caused by injecting
drug use, as the consequent reduction of the age group and greater dissemination
among heterosexual individuals; 3- third and current stage, when there is a growing
8. trend to dissemination among the heterosexuals, mainly the women (Goldgur at al.,
1999).
This last observation deserves highlighting, because it has been reported
in several countries a process of the “feminization” of the HIV/SIDA epidemic.
Regarding to the distribution of the cases according to age group, it was observed in
the last decade an ageing of it, with a persistent relevant growing of the age group
over the age of 35, in both sexes. The age group from 35 to 39 and 40 to 49, with an
increase of the incidence among women (from about 6,5 men to 1 woman, in the
1980s, to 1,7 men to 1 woman in 2001) (De Clercq. 2001).
The morphological structures of the HIV viruses (1 and 2) include
structural and functional proteins and an RNA genome protected by the viral
envelope. The envelope is made of a lipid bilayer and contains a complex protein,
known as env (Ferreira, 2002).
In the interior face, the HIV has a viral protein called p17 (matrix) and,
enclosed by this protein, there is the capsule composed by the p24 protein. In the
most internal part, it’s found the most important elements: two simple filaments of
RNA, the p7 protein (nucleocapside) and three essential enzymes, p51 (reverse
transcriptase), p11 (protease) and p31 (integrase) (Goldgur, et al., 1999).
The
transcriptase
is
an
enzyme
that
performs
a
contrary
transcription process related to the cellular standard. This enzyme polymerizes DNA
molecules from RNA molecules, exactly the opposite of what happens in the cells,
where RNA is produced from DNA (Gupta, 1979; 2003).
That’s exactly for having this enzyme, which it acts “contrary”, that the HIV
and other similar viruses are called retroviruses. After being in the host cell, the
reverse transcriptase uses the nucleotides found in the cytoplasm to compose a DNA
strand together with the virus RNA strand. The RNAse-H enzyme is responsible for
unbundling the RNA strand by hydrolysis and let the RNA simple strand be free in the
cytoplasm. The reverse transcriptase comes back to complete this DNA strand, thus
becoming the nucleotides double helix to be integrated in the host-cell DNA helped
by the integrase enzyme (Fox, 2002).
9. In Brazil, the Law 9113/96 ensured everyone the access, without its cost,
to the cocktail of drugs. Introduced in 1996, this is a combination of drugs able to
inhibit two stages of the viral replication, with a possibility of reduction in 100 times of
the virus production compared to the monotherapies used so far (Souza et al., 2003).
Depending on the conditions and the age of the patient, it can be composed by two
or more different medicines of the following classes:
(i) nucleoside reverse
transcriptase inhibitors (NRTIs); (ii) non-nucleoside reverse transcriptase inhibitors
(NNRTIs); (iii) protease inhibitors (PI) and, more recently, (iv) fusion inhibitors (FI),
and the latter was recently released to sale in Brazil (Goldgur, 1999).
The transcription process consists in the RNA synthesis, realized by an
enzymatic complex which key enzyme is the RNA polymerase, able to produce the
viral proteins in the polyproteins precursors form, long units composed of viral
enzymes and assembled structural proteins (Li,1999). The fluoroquinolones are a
class of synthetic compounds with strong antimicrobial activity. Nowadays, this class
of compounds also has been described as able to interfere in the viral transcription
process, thus preventing the replication. The K-37 fluoroquinolone has shown good
results in the inhibition of that enzyme. The temacrazine and the flavopiridol are other
compounds able to inhibit this transcription enzyme, even in chronically-infected cells
(Cocuzza, 2001).
The protease inhibitors have the function of blocking one of the HIV
components, the protease. This way, the new copies of the virus don’t infect the new
cells. The reverse transcriptase inhibitors and the protease inhibitors act inside of the
CD4 cell (Hazuda et al., 2004).
The nucleocapside protein (NCp7) is an essential protein in different
stages of the viral replication, being important in the stage that involves the reverse
transcriptase enzyme, participating of the RNA ringing (De Clercq, 2002). The AZDC
(azodicarbonamide), is a compound in clinical testing phase II and it’s able to
become inative that protein, by complexation with its zinc atoms, preventing the viral
replication of the integrase inhibitors. The integrase enzyme is fundamental in the
viral replication process, being responsible for the viral DNA integration to the hostchromosome, thus allowing for the continuation of the viral replication cycle. The “L
10. –quicórico" acid is able to inhibit the integrase enzyme activity of different kinds of
powerful HIV (De Clercq, 2001).
The fusion inhibitors (FI) represent a new approach in the combat strategy
to the capacity of the HIV replication in the organism. So that the HIV can complete
its reproductive cycle, it needs to merge itself with T lymphocytes, where it deposits
its genetic information, giving rise to a new virus. While the protease inhibitors (PIs)
and the reverse transcriptase inhibitors (NRTIs and NNRTIs) aim at interrupting the
viral replication cycle in a stage that the HIV had already infected lymphocytic target
cell, the FIs were designed to prevent the virus penetration in the lymphocytes and
the beginning of an infection (Ikemoto, et al., 2001).
The virus needs to merge itself with a T lymphocyte to multiply, and it’s
exactly this action that the fusion inhibitors prevent. With this kind of medicine, the
HIV can’t complete its reproduction cycle, because it can’t infect the T lymphocytes
and can’t create new virus copies. The fusion inhibitors act outside the host cell (CD4
lymphocyte) at an earlier stage in the virus reproduction cycle than the protease and
the reverse transcriptase inhibitors (Heralth et al., 2004).
To achieve more powerful new drugs, with better pharmacokinetic profiles,
fewer side-effects and wide range of activity to different resistant HIV viruses, new
strategies have been created. These strategies are based on the conception of new
compounds able to inhibit different points of the viral replication (Jayasuriya et al.,
2003).
In a memorandum from a WHO meeting, recommendations were made
about the research with natural substances for the treatment of AIDS. Several natural
compounds that belong to different structures have been appointed as reverse
transcriptase inhibitors, such as coumarins, flavonoids, tannins, lignins, alkaloids,
terpenes, nafto and anthraquinones and polysaccharides (Kannan et al., 2001).
Compounds of natural source can be used as therapeutic agents to a
great amount of diseases. These also can become excellent prototype-compounds to
the development of more powerful derivatives or with improvement of some biological
or physical-chemical property that allows to be used as drugs (Huang et al., 2001).
11. The bark and the bast of the Guazuma ulmifolia (mutamba) is rich in
components with pharmacological properties. In addition, these isolated principles
have been treated together with the treatment of several diseases. So, the betasitosterol act against the hypoproteinemias; the triterpenes are used as antiinflammatories (pneumonia and bronchitis); the caffeine acts as diuretics and
stimulant of the CNS (Central Nervous System) and cardiac muscles; the alkaloids
are treated as anti-microbials, painkillers, antispasmodics and CNS stimulants, the
tannins are excellent in the combat of dysentery processes (Windholz, 1983; Almeida
et al., 1998; Rizzo et al., 1990; Rizzo et al. 1999; Tridente, 2002).
Guazuma ulmifolia, popularly known as mutamba, has been used by the
population as natural medicine in almost every place that it occurs. Generally the
used parts are the bark and the leaves, however, there are some reports that the fruit
can also be useful. The bark tea is used in Brazil as a sudorific, also used in cases of
fever, cough, bronchitis, asthma, pneumonia and liver problems. Several authors
show some activities with mutamba extracts, among them they emphasise: antiglucose, anti-bacterial and anti-fungus, cytotoxic and anti-secretory activities
(Johnson, 1989; Makhija, 2002).
Guazuma shows four species distributed through South America and
Mexico, and two of them are in Brazil: Guazuma ulmifolia Lam and Guazuma crinita
Mart., both known as mutamba (Huff, 1999).
Photochemical analysis realized with the mutamba bark showed positivity
to the flavonoid and tannin groups, among others. Spectrophotometers dosing 691
nm of tannins, show that the period of the year can increase or decrease the tenor in
the mutamba (Li, 1999).
Comparing the tenor of tannin in the leaves Crataegus oxyacantha L.
(cratego), about 3%, and the ratany barks (Krameria triandra), about 10%, with the
mutamba barks, that present about 5%, the amount of tannins can be considered
reasonable (Kim et al., 2005).
The tannins are phenolic compounds characterized by their capacity of
combination with the proteins and other polymers as the polysaccharides. This
12. characteristic explains their astringency caused by the precipitations of the proteins
and by the spittle glycoproteins.
Tannins (from the French tannin) are polyphenols of plant origin, with
molecular weights generally between 500 and 3000. They inhibit the attack to the
plants from vertebrates or invertebrates herbivorous (reduction of palatability,
digestion difficulties, toxic compounds productions from tannin hydrolysis) and also
from pathogenic microorganisms. The term is widely used to designate any big
polyphenol compound containing enough hydroxyl groups and others (as carboxyl) to
form strong complexes with proteins and other macromolecules. Generally, they are
divided in two kinds: hydrolysable and condensed tannins (protoantocianidines).
Tannins from Quercus suber L. and Q. coccifera L. species show
gastroprotector effect, changing from 66 to 91%. The tannin antimicrobial properties
are well-known and documented. Tannin molecules are being tested with the
intention of finding a a new efficient drug against HIV. Kilkuskie and partners
observed that the galotannins showed inhibitory activity only in toxic concentrations,
elagitannins and condensed tannins poorly inhibited the viral replication and the
complex tannins showed powerful activity against the HIV replication. They
concluded that the anti-HIV activity showed by the tannins is due to the reverse
transcriptase inhibition, turning difficult the viral replication.
The tannin properties are linked to its capacity of forming complexes with
the proteins that participate in this case, of the tissues protection in relation to the
microbiological attacks. Besides, they confer taste properties united under the term
astringency, have anti-free radical power and have the capacity of consuming
dissolved oxygen, that is, they have interesting antioxidant properties to the
pharmacologic function and also show agri-food activity (Korolkovas, 1988; Makhija,
2001).
The link between tannins and proteins occurs, probably, through hydrogen
bridges between the tannins phenolic groups and certain proteins sites, lending a
lasting stability to these substances. To the formation of these links it’s necessary
that the tannin molecular weight is among clear limits; if it is very high, the molecule
can’t be inserted among the interfibrilar spaces of the proteins or of the
macromolecules; if it is very low, the phenolic molecule can insert, but it doesn’t form
13. a sufficient amount of links that assure the combination stability. The tannins have
been the aim of several studies, but the majority has discussed ecological
relationships between vegetables and herbivorous, because it has been suggested
that the tannin tenors can reduce the rate of predation for they become unpalatable,
taking away their natural predators. Researches on tannins biological activities
highlighted important action against certain microorganisms, as carcinogenic agents
and the ones that cause hepatic toxicity. These last effects, with no doubt, depend on
the dosage and the kind of consumed tannin. The intake of green tea and diets rich
in fruit that contain tannins, for example, has been associated with anticarcinogenic
activity. Besides, they can act as anti-inflammatories and healings, and even so, as
HIV reverse transcriptase inhibitors.
This way, if the toxicity is due to its astringency, high toxicity is closely
associated to the bigger molecular weight. However, it doesn’t happen frequently, for
example, the catechin shows bigger toxicity than the tannins, although it has low
affinity for proteins.
The complexes formed between tannins and proteins can be reversible or
irreversible. The reversible ones are established by hydrogen bridges and
hydrophobic interactions, while the irreversible ones occur in oxidative conditions by
covalent bonds (Almeida, 1999; Buckheit Jr et al., 2001).
The hydrogen bridges probably are formed between the tannin phenolic
hydroxyls and the protein amine grouping. The hydrophobic interactions occur
between the tannin aromatic rings and the aliphatic side-chains or aromatic of the
protein amino acids (Nair, 2004). It is believed that the hydrophobic interactions act
as initial traction forces in the complexation between tannins and proteins in aqueous
media. This initial association is reinforced in a second stage with the formation of a
polyfunctional net of hydrogen connections, in which each tannin molecule can make
a lot of connections with the protein, thus, acting like a polytoothed binder
(Peçanha,2002). It was still observed a correlation between the polyphenol polarity
and the kind of interaction with the bovine serum albumin (BSA) (Almeida, 1999).
The reversible complexes can be soluble or insoluble, depending on the
tannin/protein proportion, on the ph and on the environment ionic strength. The
addition of few quantities of proteins to a tannin solution produces a precipitate that is
14. dissolved with the addition of more protein (Young, 2001). Then, the maximun of
precipitation occurs when there is an excellent proportion between tannin and protein
(Li, 1999), what is, however, dependent on the quantity of bounding sites as phenolic
hydroxyls and galoia groups, inside the tannins (Almeida, 1999; Okamoto, 2000).
The different tannins capacity of complexing with the proteins vary
according to their chemical structure. It was observed that the molecular weight and
the molecule flexibility are important factors in the complexation process (Oliveira,
2000). Several studies, comparing the relative affinities of the galoia-steriles groups
with a lot of proteins showed the decreasing tendency in the penta- > tetra- > tri- > di> mono-galoil-glucose sequence, that is, the more quantity of galoia groups, the
more affinity for the proteins (Okamoto, 2000). On the other hand, some factors in
the protein structures such as conformation and polymer size also influence in the
affinity of these molecules with the tannins. Several studies show the great tannins
affinity, hydrolysable ad condensed ones, for proteins rich in proline, such as the
proteins present in the mammals spittle (Pluymers et al., 2002).
For these objectives to be achieved, it’s fundamental that the treatment
must be applied strictly and according to the doctor’s indication. If the patient doesn’t
take the medication adequately, the quantity of medicine that there is in the blood
isn’t enough to inhibit the increase of the virus and to reduce the viral load. It allows
the virus to continue destroying the CD4 cells and also to acquire resistance to the
medicines that the patient is taking in a wrong way. On the other hand, when it
happens, there is a great possibility of occurring resistance to other medicines that
the patient isn’t taking, which belong to the same classes of those that he is taking –
it’s called Cross-Resistance (Pommier, 2000).
15. 3. METHODOLOGY
This subject is a qualitative approach, performed from a collection of data
related to the theme, based on information found in books, articles, specialized
scientific magazines, monographs, resource and illustration books and on
observation.
To MINAYO (2002, 46):
The qualitative survey answers very private questions (...),
works with the deepest relation and phenomena universe that
can’t be reduced to several variable operationalizations.
The scene of the research is a private laboratory. Previously it will be
asked authorization to the accomplishment of this scientific research, as well it will be
submitted to the ethic and survey committee of the institution.
To acquire data in this study, tests of the low molecular weight tannin
dosages will be done, in mice, extracted from the Guazuma ulmifolia; then,
depending on the results, it will address the possibilities of using it in human beings,
considering the guiding questions of the survey involving human beings.
RESOLUTION N° 196/96 FROM THE BRAZILIAN DEPARTMENT OF HEALTH that
regulates the research involving human beings and it will be put under evaluation by
the Research Ethics Committee of the institution responsible for the research.
The search data will be grouped in categories aimed at the results, and
will suffer analyses based on thematic benchmark about the subject.
16. 4.
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