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History of drug resistance
1. Vaishali singh,bsc,125145
Abstract
Opioid receptors, besides mediating the effects of analgesic compounds, are involved in drug
addiction. Although a large amount of work has been done studying these receptors in mammals,
little information has been obtained from nonmammalian vertebrates. We have studied the
regional distribution in the central nervous system (CNS) of the zebrafish of the recently cloned
delta-opioid receptor homologue ZFOR1 using nonradioactive in situ hybridization. Our findings
show that different nuclei within the main subdivisions of the brain displayed specific mRNA
signal. The expression is widespread throughout the brain, but only specific cells within each
nucleus displayed ZFOR1. Stained cells were abundant in the telencephalon, both in the
olfactory bulb and telencephalic hemispheres, and in the diencephalon, where expression was
observed in all the different subdivisions. In the mesencephalon, expression of ZFOR1 was
abundant in the periventricular layer of the optic tectum. In the cerebellum, expression of ZFOR1
was detected in valvula cerebelli, corpus cerebelli, and lobus vestibulolateralis in both granule
and Purkinje cells. In the myelencephalon, cells expressing ZFOR1 were also distributed in the
octavolateralis area, the reticular formation, and the raphe nuclei, among others. Also, ZFOR1
was detected in cells of the dorsal and ventral horn of the spinal cord. This work presents the first
detailed distribution of a delta-opioid receptor in the CNS of zebrafish. Distribution of ZFOR1
expression is compared with that of the delta-opioid receptor described in mammals.
Copyright 1999 Wiley-Liss, Inc.
History of Drug Resistance
So far, no preventative vaccination against malaria exists, and its control depends heavily upon
antimalarial drugs that kill parasites inside the human body. Malaria has been noted for more
than 4,000 years. In ancient China, India, the Middle East, Greece, and Rome, malaria and its
possible treatments were documented. Ancient Chinese used a treatment based on artemisinin
(documented 168 BC), the active ingredient in some high-end drugs nowadays. Treatments with
Quinine are known to the western world since the early 17th century. In British colonies, tonic
water (which contains large amounts of Quinine) was mixed with gin and became a popular
drink.
The discovery of Chloroquine (CQ) in the 1930s revolutionized malaria treatments. CQ was the
most widely-used drug from the early 1950s to until the 1990s. After about ten years of use,
mutations within P. falciparum that conferred resistance to CQ arose independently in Columbia
and Thailand. Since then CQ-resistant mutations have been spreading quickly through most
endemic areas. CQ clears out resistant parasites less efficiently from the human body than
sensitive (non-resistant) parasites. Hence, infections with resistant parasites result in increased
morbidity and mortality.
Sulfadoxine-pyrimethamine (SP), a combination of two drugs, replaced CQ. However, resistance
to SP evolved rapidly and now occurs at high frequency in major malarious regions
(Laxminarayan 2004). Currently, alternative drugs (e.g., artemisinin-based combination
therapies) are available and others continue to be developed. However, higher production costs
2. Vaishali singh,bsc,125145
Abstract
Opioid receptors, besides mediating the effects of analgesic compounds, are involved in drug
addiction. Although a large amount of work has been done studying these receptors in mammals,
little information has been obtained from nonmammalian vertebrates. We have studied the
regional distribution in the central nervous system (CNS) of the zebrafish of the recently cloned
delta-opioid receptor homologue ZFOR1 using nonradioactive in situ hybridization. Our findings
show that different nuclei within the main subdivisions of the brain displayed specific mRNA
signal. The expression is widespread throughout the brain, but only specific cells within each
nucleus displayed ZFOR1. Stained cells were abundant in the telencephalon, both in the
olfactory bulb and telencephalic hemispheres, and in the diencephalon, where expression was
observed in all the different subdivisions. In the mesencephalon, expression of ZFOR1 was
abundant in the periventricular layer of the optic tectum. In the cerebellum, expression of ZFOR1
was detected in valvula cerebelli, corpus cerebelli, and lobus vestibulolateralis in both granule
and Purkinje cells. In the myelencephalon, cells expressing ZFOR1 were also distributed in the
octavolateralis area, the reticular formation, and the raphe nuclei, among others. Also, ZFOR1
was detected in cells of the dorsal and ventral horn of the spinal cord. This work presents the first
detailed distribution of a delta-opioid receptor in the CNS of zebrafish. Distribution of ZFOR1
expression is compared with that of the delta-opioid receptor described in mammals.
Copyright 1999 Wiley-Liss, Inc.
limit their widespread application in major endemic areas. The evolution of resistance against
affordable drugs incurs an enormous societal cost for fighting the spread of the disease. Facing
this reality, the focus of public health policy should be shifted to increasing the sustainability of
treatment regimes by delaying the emergence and spread of drug resistance as much and early as
possible.
Avoiding Drug Resistance
Is it possible to prevent or delay the spread of anti-malaria drug resistance? The answer requires
approaches that integrate the disease ecology, epidemiology, genetics, and evolutionary biology
of malaria. Such interdisciplinary research started to dissect the dynamics of drug-resistance
evolution under various clinical and demographic settings. The complex problem of identifying
key determinants in the spread of resistance could be tackled from many starting points.
However, a critical path to the heart of the problem is to recognize that the evolution of drug
resistance is an example of Darwinian evolution by natural selection.
From the parasites' point of view, drug-treated human hosts represent a novel harsh environment.
Any mutation in their genome that reduces the rate at which drugs eliminate them from the host
is beneficial to the parasites and will be subject to positive selection. Biological conditions
known to delay the propagation of beneficial mutations would provide clues for designing
optimal drug-deployment policies that should slow down the spread of resistant parasites. Hence,
some theoretical concepts and tools of population genetics to investigate positive selection in
3. Vaishali singh,bsc,125145
Abstract
Opioid receptors, besides mediating the effects of analgesic compounds, are involved in drug
addiction. Although a large amount of work has been done studying these receptors in mammals,
little information has been obtained from nonmammalian vertebrates. We have studied the
regional distribution in the central nervous system (CNS) of the zebrafish of the recently cloned
delta-opioid receptor homologue ZFOR1 using nonradioactive in situ hybridization. Our findings
show that different nuclei within the main subdivisions of the brain displayed specific mRNA
signal. The expression is widespread throughout the brain, but only specific cells within each
nucleus displayed ZFOR1. Stained cells were abundant in the telencephalon, both in the
olfactory bulb and telencephalic hemispheres, and in the diencephalon, where expression was
observed in all the different subdivisions. In the mesencephalon, expression of ZFOR1 was
abundant in the periventricular layer of the optic tectum. In the cerebellum, expression of ZFOR1
was detected in valvula cerebelli, corpus cerebelli, and lobus vestibulolateralis in both granule
and Purkinje cells. In the myelencephalon, cells expressing ZFOR1 were also distributed in the
octavolateralis area, the reticular formation, and the raphe nuclei, among others. Also, ZFOR1
was detected in cells of the dorsal and ventral horn of the spinal cord. This work presents the first
detailed distribution of a delta-opioid receptor in the CNS of zebrafish. Distribution of ZFOR1
expression is compared with that of the delta-opioid receptor described in mammals.
Copyright 1999 Wiley-Liss, Inc.
plant and animal populations have been employed recently to assist in solving the problem of
anti-malarial drug resistance (Escalante et al. 2009).
At first, the population genetic explanation for the emergence of resistance seemed
straightforward: in the laboratory, the rate of spontaneous mutation from drug sensitive to
resistant alleles was found to be 10-8 per replication. If an infected host carries 1010 parasites in
the body, at least 100 of them will be drug-resistant, and their number will keep increasing due to
their selective advantage over sensitive parasites within drug-treated hosts. In conclusion, new
resistant parasite strains would emerge readily whenever the drug is introduced to an endemic
region. However, the analysis of DNA variation among resistant parasites revealed that severe
resistance, for both CQ and SP, spread from only a few independent strains worldwide (Roper et
al. 2003). This discrepancy arises because the simple evolutionary model above neglects the
complexity of the Plasmodium life cycle and the pharmacodynamics of drugs. Furthermore, it
points to the problem of conventional population genetics modeling that typically traces the
relative frequency, rather than absolute count, of variants over time.
First, despite the abundance of merozoites in the patients' blood, very few of these produce
gametocytes that ultimately transfer to mosquitoes (Hastings 2004). Thus the probability that a
resistant mutant is included among those gametocytes is very small, unless the relative and
absolute frequencies of resistant parasites greatly increase immediately after drug treatment
(which is unlikely for several reasons; see below). Second, more importantly, resistance against a
particular drug is initially incomplete, but builds up from low to high levels as successive
mutations occur within the parasite. An initial resistant mutation creates a strain that survives
better than sensitive parasites but is still eliminated under the normal drug concentration (i.e., the
4. Vaishali singh,bsc,125145
Abstract
Opioid receptors, besides mediating the effects of analgesic compounds, are involved in drug
addiction. Although a large amount of work has been done studying these receptors in mammals,
little information has been obtained from nonmammalian vertebrates. We have studied the
regional distribution in the central nervous system (CNS) of the zebrafish of the recently cloned
delta-opioid receptor homologue ZFOR1 using nonradioactive in situ hybridization. Our findings
show that different nuclei within the main subdivisions of the brain displayed specific mRNA
signal. The expression is widespread throughout the brain, but only specific cells within each
nucleus displayed ZFOR1. Stained cells were abundant in the telencephalon, both in the
olfactory bulb and telencephalic hemispheres, and in the diencephalon, where expression was
observed in all the different subdivisions. In the mesencephalon, expression of ZFOR1 was
abundant in the periventricular layer of the optic tectum. In the cerebellum, expression of ZFOR1
was detected in valvula cerebelli, corpus cerebelli, and lobus vestibulolateralis in both granule
and Purkinje cells. In the myelencephalon, cells expressing ZFOR1 were also distributed in the
octavolateralis area, the reticular formation, and the raphe nuclei, among others. Also, ZFOR1
was detected in cells of the dorsal and ventral horn of the spinal cord. This work presents the first
detailed distribution of a delta-opioid receptor in the CNS of zebrafish. Distribution of ZFOR1
expression is compared with that of the delta-opioid receptor described in mammals.
Copyright 1999 Wiley-Liss, Inc.
initial dose of drug given to the patient). Therefore, the drug kills sensitive and resistant
parasites. However, while its absolute number decreases rapidly (say from 100 to 0), resistant
parasites may produce a gametocyte that is successfully transferred to a mosquito, which would
happen very rarely.
Next, this ‘lucky' resistant parasite in the mosquito still faces elimination: after the mosquito
infects a host, a regular drug dosage will likely kill the drug resistant individuals. If the infected
host is untreated, drug-sensitive will outcompete drug-resistant parasites (see below). However,
the drug concentration in treated hosts decays over time, as does its effect on parasite growth. At
an intermediate concentration, resistant parasites can increase their absolute number while the
drug kills sensitive parasites. As mosquitoes transfer resistant sporozoites, resistant parasites
survive in a host with intermediate drug concentration, and will be further transmitted. If drugs
decay slowly, more hosts with intermediate concentration are available, and resistant parasites
have more opportunities to establish themselves (Hastings et al. 2002). This may explain why
arteminisin, which decays very rapidly, remained effective for more than 25 years in South East
Asia.
Once a drug-resistance mutation appears and overcomes the hurdles in initial establishment, its
frequency increases rapidly because of its selective advantage over drug-sensitive parasites. This
selective advantage depends on the proportion of drug-treated infections, because resistant
mutations are advantageous only in drug-treated hosts. When they co-infect an untreated host,
drug-sensitive parasites are likely to have an advantage over resistant ones because drug
resistance comes with "metabolic costs" that slow down their growth.
5. Vaishali singh,bsc,125145
Abstract
Opioid receptors, besides mediating the effects of analgesic compounds, are involved in drug
addiction. Although a large amount of work has been done studying these receptors in mammals,
little information has been obtained from nonmammalian vertebrates. We have studied the
regional distribution in the central nervous system (CNS) of the zebrafish of the recently cloned
delta-opioid receptor homologue ZFOR1 using nonradioactive in situ hybridization. Our findings
show that different nuclei within the main subdivisions of the brain displayed specific mRNA
signal. The expression is widespread throughout the brain, but only specific cells within each
nucleus displayed ZFOR1. Stained cells were abundant in the telencephalon, both in the
olfactory bulb and telencephalic hemispheres, and in the diencephalon, where expression was
observed in all the different subdivisions. In the mesencephalon, expression of ZFOR1 was
abundant in the periventricular layer of the optic tectum. In the cerebellum, expression of ZFOR1
was detected in valvula cerebelli, corpus cerebelli, and lobus vestibulolateralis in both granule
and Purkinje cells. In the myelencephalon, cells expressing ZFOR1 were also distributed in the
octavolateralis area, the reticular formation, and the raphe nuclei, among others. Also, ZFOR1
was detected in cells of the dorsal and ventral horn of the spinal cord. This work presents the first
detailed distribution of a delta-opioid receptor in the CNS of zebrafish. Distribution of ZFOR1
expression is compared with that of the delta-opioid receptor described in mammals.
Copyright 1999 Wiley-Liss, Inc.
These population genetic considerations suggest conditions that would maximally delay the
evolution of drug resistance: an anti-malarial drug should be strong enough to kill both sensitive
and partially-resistant parasites very quickly. Moreover, the drug should decay fast enough to
shorten the time-window of sub-optimal drug concentration. Additionally, comprehensive
preventative treatments and the use of counterfeits drugs should be avoided to reduce the
selective advantage of resistant mutations (Mackinnon 2005). Furthermore, limited contact
between infected hosts and mosquitoes while the drug decays should delay the spread of resistant
parasites.
Chikunguniy
Chikungunya (English pronunciation: /ˌtʃɪkənˈgʊɲə/ CHI-kən-GUUN-yə; Makonde for "that which
bends up") is an infection caused by the Chikungunya virus. It causes an illness with an acute
febrile phase lasting two to five days, followed by a longer period of joint pains in the
extremities; this pain may persist for years in some cases.[1][2]
The disease is transmitted similarly to dengue fever to humans by virus-carrying Aedes
mosquitoes.[3] Specifically, two species of mosquitoes, A. albopictus and A. aegypti are extrinsic
hosts (vectors) of chikungunya virus.[4] The strain of chikungunya spreading to the US from the
Caribbean is most easily spread by A. aegypti. Concern exists that this strain of chikungunya
could mutate to make the A. albopictus vector more efficient. If this mutation were to occur,
chikungunya would be more of a public health concern to the US. The A. albopictus or Asian
tiger mosquito is more widespread in the US and is more aggressive than the A. aegypti.[5] It is
6. Vaishali singh,bsc,125145
Abstract
Opioid receptors, besides mediating the effects of analgesic compounds, are involved in drug
addiction. Although a large amount of work has been done studying these receptors in mammals,
little information has been obtained from nonmammalian vertebrates. We have studied the
regional distribution in the central nervous system (CNS) of the zebrafish of the recently cloned
delta-opioid receptor homologue ZFOR1 using nonradioactive in situ hybridization. Our findings
show that different nuclei within the main subdivisions of the brain displayed specific mRNA
signal. The expression is widespread throughout the brain, but only specific cells within each
nucleus displayed ZFOR1. Stained cells were abundant in the telencephalon, both in the
olfactory bulb and telencephalic hemispheres, and in the diencephalon, where expression was
observed in all the different subdivisions. In the mesencephalon, expression of ZFOR1 was
abundant in the periventricular layer of the optic tectum. In the cerebellum, expression of ZFOR1
was detected in valvula cerebelli, corpus cerebelli, and lobus vestibulolateralis in both granule
and Purkinje cells. In the myelencephalon, cells expressing ZFOR1 were also distributed in the
octavolateralis area, the reticular formation, and the raphe nuclei, among others. Also, ZFOR1
was detected in cells of the dorsal and ventral horn of the spinal cord. This work presents the first
detailed distribution of a delta-opioid receptor in the CNS of zebrafish. Distribution of ZFOR1
expression is compared with that of the delta-opioid receptor described in mammals.
Copyright 1999 Wiley-Liss, Inc.
known that monkeys, birds, cattle, and rodents are animal reservoirs for the virus.[6][7] This is in
contrast to dengue, in which only humans and primates are host reservoirs.[8]
The best means of prevention is overall mosquito control and the avoidance of bites by any
infected mosquitoes.[9] No specific treatment is known, but medications can be used to reduce
symptoms.[9] Rest and fluids may also be useful.[10]
Signs and symptoms
The incubation period of chikungunya disease ranges from 2 to 12 days, typically two to three.
The majority of those infected will develop symptoms.[11] Symptoms include a fever up to 40 °C
(104 °F), petechial or maculopapular rash of the trunk and occasionally the limbs, and arthralgia
or arthritis affecting multiple joints.[12] Other nonspecific symptoms can include headache,
nausea, vomiting, conjunctivitis, slight photophobia, and partial loss of taste.[13] Ocular
inflammation from chikungunya may present as iridocyclitis, or uveitis. Retinal lesions may also
occur.[14] Swelling of legs is observed in many people, the cause of which remains obscure as it
is not related to any cardiovascular, renal, or hepatic abnormalities.
Typically, the fever lasts for two days and then ends abruptly. However, other symptoms, namely
joint pain, intense headache, insomnia and an extreme degree of prostration, last for a variable
period, usually about five to seven days.[12] People have complained of joint pains for much
longer time periods, some as long as two years, depending on their age.[15][16] Recovery from the
disease varies by age. Younger people recover within five to 15 days; middle-aged people
recover in 1.0 to 2.5 months. Recovery is longer for the elderly. The severity of the disease, as
7. Vaishali singh,bsc,125145
Abstract
Opioid receptors, besides mediating the effects of analgesic compounds, are involved in drug
addiction. Although a large amount of work has been done studying these receptors in mammals,
little information has been obtained from nonmammalian vertebrates. We have studied the
regional distribution in the central nervous system (CNS) of the zebrafish of the recently cloned
delta-opioid receptor homologue ZFOR1 using nonradioactive in situ hybridization. Our findings
show that different nuclei within the main subdivisions of the brain displayed specific mRNA
signal. The expression is widespread throughout the brain, but only specific cells within each
nucleus displayed ZFOR1. Stained cells were abundant in the telencephalon, both in the
olfactory bulb and telencephalic hemispheres, and in the diencephalon, where expression was
observed in all the different subdivisions. In the mesencephalon, expression of ZFOR1 was
abundant in the periventricular layer of the optic tectum. In the cerebellum, expression of ZFOR1
was detected in valvula cerebelli, corpus cerebelli, and lobus vestibulolateralis in both granule
and Purkinje cells. In the myelencephalon, cells expressing ZFOR1 were also distributed in the
octavolateralis area, the reticular formation, and the raphe nuclei, among others. Also, ZFOR1
was detected in cells of the dorsal and ventral horn of the spinal cord. This work presents the first
detailed distribution of a delta-opioid receptor in the CNS of zebrafish. Distribution of ZFOR1
expression is compared with that of the delta-opioid receptor described in mammals.
Copyright 1999 Wiley-Liss, Inc.
well as its duration, is less in younger people and pregnant women. In pregnant women, no
untoward effects are noticed after the infection.
Chronic disease
Observations during recent epidemics have suggested chikungunya may cause long-term
symptoms following acute infection. During the La Reunion outbreak in 2006, more than 50% of
subjects over the age of 45 reported long-term musculoskeletal pain[17] with up to 60% of people
reporting prolonged arthralgia three years following initial infection.[18] A study of imported
cases in France reported that 59% of people still suffered from arthralgia two years after acute
infection.[19] Following a local epidemic of chikungunya in Italy, 66% of people reported
muscles pains, joint pains, or asthenia at one year after acute infection.[20] Long-term symptoms
are not an entirely new observation; long-term arthritis was observed following an outbreak in
1979.[21] Common predictors of prolonged symptoms are increased age and prior
rheumatological disease.[17][18][20][22] The cause of these chronic symptoms is currently not fully
known. Markers of autoimmune or rheumatoid disease have not been found in people reporting
chronic symptoms.[18][23] However, some evidence from humans and animal models suggests
chikungunya may be able to establish chronic infections within the host. Viral antigen was
detected in a muscle biopsy of a people suffering a recurrent episode of disease three months
after initial onset.[24] Additionally, viral antigen and RNA were found in synovial macrophages
of a person during a relapse of musculoskeletal disease 18 months after initial infection.[25]
Several animal models have also suggested chikungunya virus may establish persistent
infections. In a mouse model, viral RNA was detected specifically in joint-associated tissue for at
least 16 weeks after inoculation, and was associated with chronic synovitis.[26] Similarly, another
8. Vaishali singh,bsc,125145
Abstract
Opioid receptors, besides mediating the effects of analgesic compounds, are involved in drug
addiction. Although a large amount of work has been done studying these receptors in mammals,
little information has been obtained from nonmammalian vertebrates. We have studied the
regional distribution in the central nervous system (CNS) of the zebrafish of the recently cloned
delta-opioid receptor homologue ZFOR1 using nonradioactive in situ hybridization. Our findings
show that different nuclei within the main subdivisions of the brain displayed specific mRNA
signal. The expression is widespread throughout the brain, but only specific cells within each
nucleus displayed ZFOR1. Stained cells were abundant in the telencephalon, both in the
olfactory bulb and telencephalic hemispheres, and in the diencephalon, where expression was
observed in all the different subdivisions. In the mesencephalon, expression of ZFOR1 was
abundant in the periventricular layer of the optic tectum. In the cerebellum, expression of ZFOR1
was detected in valvula cerebelli, corpus cerebelli, and lobus vestibulolateralis in both granule
and Purkinje cells. In the myelencephalon, cells expressing ZFOR1 were also distributed in the
octavolateralis area, the reticular formation, and the raphe nuclei, among others. Also, ZFOR1
was detected in cells of the dorsal and ventral horn of the spinal cord. This work presents the first
detailed distribution of a delta-opioid receptor in the CNS of zebrafish. Distribution of ZFOR1
expression is compared with that of the delta-opioid receptor described in mammals.
Copyright 1999 Wiley-Liss, Inc.
study reported detection of a viral reporter gene in joint tissue of mice for weeks after
inoculation.[27] In a nonhuman primate model, chikungunya virus was found to persist in the
spleen for at least six weeks.[28]
Diagnosis
Common laboratory tests for chikungunya include RT-PCR, virus isolation, and serological tests.
Virus isolation provides the most definitive diagnosis, but takes one to two weeks for
completion and must be carried out in biosafety level III laboratories. [49] The technique involves
exposing specific cell lines to samples from whole blood and identifying chikungunya virus-specific
responses.
RT-PCR using nested primer pairs is used to amplify several chikungunya-specific genes from
whole blood. Results can be determined in one to two days. [49]
Serological diagnosis requires a larger amount of blood than the other methods, and uses an
ELISA assay to measure chikungunya-specific IgM levels. Results require two to three days, and
false positives can occur with infection via other related viruses, such as o'nyong'nyong virus
and Semliki Forest virus.[49]
Prevention
An A. aegypti mosquito biting a person
The most effective means of prevention are protection against contact with the disease-carrying
mosquitoes and mosquito control.[9] These include using insect repellents with substances such
9. Vaishali singh,bsc,125145
Abstract
Opioid receptors, besides mediating the effects of analgesic compounds, are involved in drug
addiction. Although a large amount of work has been done studying these receptors in mammals,
little information has been obtained from nonmammalian vertebrates. We have studied the
regional distribution in the central nervous system (CNS) of the zebrafish of the recently cloned
delta-opioid receptor homologue ZFOR1 using nonradioactive in situ hybridization. Our findings
show that different nuclei within the main subdivisions of the brain displayed specific mRNA
signal. The expression is widespread throughout the brain, but only specific cells within each
nucleus displayed ZFOR1. Stained cells were abundant in the telencephalon, both in the
olfactory bulb and telencephalic hemispheres, and in the diencephalon, where expression was
observed in all the different subdivisions. In the mesencephalon, expression of ZFOR1 was
abundant in the periventricular layer of the optic tectum. In the cerebellum, expression of ZFOR1
was detected in valvula cerebelli, corpus cerebelli, and lobus vestibulolateralis in both granule
and Purkinje cells. In the myelencephalon, cells expressing ZFOR1 were also distributed in the
octavolateralis area, the reticular formation, and the raphe nuclei, among others. Also, ZFOR1
was detected in cells of the dorsal and ventral horn of the spinal cord. This work presents the first
detailed distribution of a delta-opioid receptor in the CNS of zebrafish. Distribution of ZFOR1
expression is compared with that of the delta-opioid receptor described in mammals.
Copyright 1999 Wiley-Liss, Inc.
as DEET (N,N-diethyl-meta-toluamide; also known as N,N'-diethyl-3-methylbenzamide or
NNDB), icaridin (also known as picaridin and KBR3023), PMD (p-menthane-3,8-diol, a
substance derived from the lemon eucalyptus tree), or IR3535. Wearing bite-proof long sleeves
and trousers also offers protection.
In addition, garments can be treated with pyrethroids, a class of insecticides that often has
repellent properties. Vaporized pyrethroids (for example in mosquito coils) are also insect
repellents. Securing screens on windows and doors will help to keep mosquitoes out of the
house. In the case of the day-active A. aegypti and A. albopictus, however, this will have only a
limited effect, since many contacts between the mosquitoes and humans occur outside.
Vaccine
Currently, no approved vaccines are available. A phase-II vaccine trial used a live, attenuated
virus, to develop viral resistance in 98% of those tested after 28 days and 85% still showed
resistance after one year.[51] However, 8% of people reported transient joint pain, and attenuation
was found to be due to only two mutations in the E2 glycoprotein.[52] Alternative vaccine
strategies have been developed, and show efficacy in mouse models, but have so far not reached
clinical trials.[53][54] In August 2014 it was revealed researchers at the National Institute of
Allergy and Infectious Diseases were testing an experimental vaccine.[55] If a vaccine becomes
available, public health officials wi
10. Vaishali singh,bsc,125145
Abstract
Opioid receptors, besides mediating the effects of analgesic compounds, are involved in drug
addiction. Although a large amount of work has been done studying these receptors in mammals,
little information has been obtained from nonmammalian vertebrates. We have studied the
regional distribution in the central nervous system (CNS) of the zebrafish of the recently cloned
delta-opioid receptor homologue ZFOR1 using nonradioactive in situ hybridization. Our findings
show that different nuclei within the main subdivisions of the brain displayed specific mRNA
signal. The expression is widespread throughout the brain, but only specific cells within each
nucleus displayed ZFOR1. Stained cells were abundant in the telencephalon, both in the
olfactory bulb and telencephalic hemispheres, and in the diencephalon, where expression was
observed in all the different subdivisions. In the mesencephalon, expression of ZFOR1 was
abundant in the periventricular layer of the optic tectum. In the cerebellum, expression of ZFOR1
was detected in valvula cerebelli, corpus cerebelli, and lobus vestibulolateralis in both granule
and Purkinje cells. In the myelencephalon, cells expressing ZFOR1 were also distributed in the
octavolateralis area, the reticular formation, and the raphe nuclei, among others. Also, ZFOR1
was detected in cells of the dorsal and ventral horn of the spinal cord. This work presents the first
detailed distribution of a delta-opioid receptor in the CNS of zebrafish. Distribution of ZFOR1
expression is compared with that of the delta-opioid receptor described in mammals.
Copyright 1999 Wiley-Liss, Inc.
Treatment
Currently, no specific treatment is available.[9] Attempts to relieve the symptoms include the use
of NSAIDs such as naproxen or paracetamol (acetaminophen) and fluids.[9] Aspirin is not
recommended.[57]
Chronic arthritis
In those who have more than two weeks of arthritis, ribavirin may be useful.[9] The effect of
chloroquine is not clear.[9] It does not appear to help acute disease, but tentative evidence
indicates it might help those with chronic arthritis.[9] Steroids do not appear useful, either.[
History
The word 'chikungunya' is thought to derive from a description in the Makonde language,
meaning "that which bends up", of the contorted posture of people affected with the severe joint
pain and arthritic symptoms associated with this disease.[86] The disease was first described by
Marion Robinson[87] and W.H.R. Lumsden[88] in 1955, following an outbreak in 1952 on the
Makonde Plateau, along the border between Mozambique and Tanganyika (the mainland part of
modern day Tanzania).
According to the initial 1955 report about the epidemiology of the disease, the term
'chikungunya' is derived from the Makonde root verb kungunyala, meaning to dry up or become
contorted. In concurrent research, Robinson glossed the Makonde term more specifically as "that
11. Vaishali singh,bsc,125145
Abstract
Opioid receptors, besides mediating the effects of analgesic compounds, are involved in drug
addiction. Although a large amount of work has been done studying these receptors in mammals,
little information has been obtained from nonmammalian vertebrates. We have studied the
regional distribution in the central nervous system (CNS) of the zebrafish of the recently cloned
delta-opioid receptor homologue ZFOR1 using nonradioactive in situ hybridization. Our findings
show that different nuclei within the main subdivisions of the brain displayed specific mRNA
signal. The expression is widespread throughout the brain, but only specific cells within each
nucleus displayed ZFOR1. Stained cells were abundant in the telencephalon, both in the
olfactory bulb and telencephalic hemispheres, and in the diencephalon, where expression was
observed in all the different subdivisions. In the mesencephalon, expression of ZFOR1 was
abundant in the periventricular layer of the optic tectum. In the cerebellum, expression of ZFOR1
was detected in valvula cerebelli, corpus cerebelli, and lobus vestibulolateralis in both granule
and Purkinje cells. In the myelencephalon, cells expressing ZFOR1 were also distributed in the
octavolateralis area, the reticular formation, and the raphe nuclei, among others. Also, ZFOR1
was detected in cells of the dorsal and ventral horn of the spinal cord. This work presents the first
detailed distribution of a delta-opioid receptor in the CNS of zebrafish. Distribution of ZFOR1
expression is compared with that of the delta-opioid receptor described in mammals.
Copyright 1999 Wiley-Liss, Inc.
which bends up". Subsequent authors apparently overlooked the references to the Makonde
language and assumed the term derived from Swahili, the lingua franca of the region. The
erroneous attribution of the term as a Swahili word has been repeated in numerous print sources.
Many erroneous spellings of the name of the disease are in common use.
Since its discovery in Tanganyika, Africa, in 1952, chikungunya virus outbreaks have occurred
occasionally in Africa, South Asia, and Southeast Asia, but recent outbreaks have spread the
disease over a wider range.
The first recorded outbreak of this disease may have been in 1779.[89] This is in agreement with
the molecular genetics evidence that suggests it evolved around the year 1700.[90]