Persius/hicric huggingface dataset:
Trifluridine clinical pharmacology

# Clinical Pharmacology
Trifluridine is a fluorinated pyrimidine nucleoside with in vitro and in vivo activity against herpes simplex virus, types 1 and 2 and vaccinia virus. Some strains of adenovirus are also inhibited in vitro.
VIROPTIC is also effective in the treatment of epithelial keratitis that has not responded clinically to the topical administration of idoxuridine or when ocular toxicity or hypersensitivity to idoxuridine has occurred. In a smaller number of patients found to be resistant to topical vidarabine, VIROPTIC was also effective.
Trifluridine interferes with DNA synthesis in cultured mammalian cells. However, its antiviral mechanism of action is not completely known.
In vitro perfusion studies on excised rabbit cornea have shown that trifluridine penetrates the intact cornea as evidenced by recovery of parental drug and its major metabolite, 5-carboxy-2'-deoxyuridine, on the endothelial side of the cornea. Absence of the corneal epithelium enhances the penetration of trifluridine approximately two-fold.
Intraocular penetration of trifluridine occurs after topical instillation of VIROPTIC into human eyes. Decreased corneal integrity or stromal or uveal inflammation may enhance the penetration of trifluridine into the aqueous humor. Unlike the results of ocular penetration of trifluridine in vitro, 5-carboxy-2'-deoxyuridine was not found in detectable concentrations within the aqueous humor of the human eye.
Systemic absorption of trifluridine following therapeutic dosing with VIROPTIC appears to be negligible. No detectable concentrations of trifluridine or 5-carboxy-2'-deoxyuridine were found in the sera of adult healthy normal subjects who had VIROPTIC instilled into their eyes seven times daily for 14 consecutive days.
Trimethoprim indications and usage

# Indications And Usage
PRIMSOL Solution is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below.

## Pediatric Patients
Acute Otitis Media
For the treatment of acute otitis media due to susceptible strains of Streptococcus pneumoniae and Haemophilus influenzae.
NOTE: Moraxella catarrhalis isolates were found consistently resistant to trimethoprim in vitro. Therefore, when infection with Moraxella catarrhalis is suspected, the use of alternative antimicrobial agents should be considered. PRIMSOL is not indicated for prophylactic or prolonged administration in otitis media at any age.

## Adults
Urinary Tract Infections
For the treatment of initial episodes of uncomplicated urinary tract infections due to susceptible strains of the following organisms: Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter species and coagulase-negative Staphylococcus species, including S. saprophyticus.
Cultures and susceptibility tests should be performed to determine the susceptibility of the bacteria to trimethoprim. Therapy may be initiated prior to obtaining the results of these tests.
Uroporphyrinogen III decarboxylase
Uroporphyrinogen III decarboxylase (uroporphyrinogen decarboxylase, or UROD) is an enzyme (EC 4.1.1.37) that in humans is encoded by the UROD  gene.

# Function
Uroporphyrinogen III decarboxylase is a homodimeric enzyme (PDB: 1URO) that catalyzes the fifth step in heme biosynthesis, which corresponds to the elimination of carboxyl groups from the four acetate side chains of uroporphyrinogen III to yield coproporphyrinogen III:

# Clinical significance
Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoietic porphyria.

# Mechanism
At low substrate concentrations, the reaction is believed to follow an ordered route, with the sequential removal of CO2 from the D, A, B, and C rings, whereas at higher substrate/enzyme levels a random route seems to be operative. The enzyme functions as a dimer in solution, and both the enzymes from human and tobacco have been crystallized and solved at good resolutions.
UroD is regarded as an unusual decarboxylase, since it performs decarboxylations without the intervention of any cofactors, unlike the vast majority of decarboxylases. Its mechanism has recently been proposed to proceed through substrate protonation by an arginine residue. A 2008 report demonstrated that the uncatalyzed rate for UroD's reaction is 1019 s1, so at pH 10 the rate acceleration of UroD relative to the uncatalyzed rate, i.e. catalytic proficiency, is the largest for any enzyme known, 6 x 1024 M1.
Von Hippel-Lindau tumor suppressor

# Overview
The Von Hippel-Lindau tumor suppressor protein is a protein whose inactivation is associated with Von Hippel-Lindau disease.
Von Hippel-Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign tumors of the eye, brain, spinal cord, kidney, pancreas, and adrenal glands. A germline mutation of this gene is the basis of familial inheritance of VHL syndrome. The protein encoded by this gene is a component of the protein complex that includes elongin B, elongin C, and cullin-2, and possesses ubiquitin ligase E3 activity. This protein is involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the regulation of gene expression by oxygen. RNA polymerase II subunit POLR2G/RPB7 is also reported to be a target of this protein. Alternatively spliced transcript variants encoding distinct isoforms have been observed.
The disease is caused by mutations of the VHL gene on the short arm of the third chromosome (3p26-p25).

# Function
The resultant protein is produced in two forms, an 18 kDa and a 30 kDa protein that functions as a tumor suppressor gene. The main action of the VHL protein is thought to be its E3 ubiquitin ligase activity that results in specific target proteins being 'marked' for degradation.
The most researched of these targets is hypoxia inducible factor 1a (HIF1a), a transcription factor that induces the expression of a number of angiogenesis related factors. (However, VHL does play other roles in tumor regulation.)

# Pathology
It stands to reason that the loss of VHL protein activity results in an increased amount of HIF1a, and thus increased levels of angiogenic factors, including VEGF and PDGF. In turn, this leads to unregulated blood vessel growth, one of the prerequisites of a tumour.
Valacyclovir indications and usage

# Indications and Usage

## Adult Patients
Cold Sores (Herpes Labialis): VALTREX (valacyclovir hydrochloride) Caplets are indicated for treatment of cold sores (herpes labialis). The efficacy of VALTREX initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established.
Genital herpes: Initial Episode: VALTREX is indicated for treatment of the initial episode of genital herpes in immunocompetent adults. The efficacy of treatment with VALTREX when initiated more than 72 hours afAt of signs and symptoms has not been established.
Suppressive Therapy: VALTREX is indicated for chronic suppressive therapy of recurrent episodes of genital herpes in immunocompetent and in HIV-1infected adults. The efficacy and safety of VALTREX for the suppression of genital herpes beyond 1 year in immunocompetent patients and beyond 6 months in HIV-1infected patients have not been established.
Reduction of Transmission: VALTREX is indicated for the reduction of transmission of genital herpes in immunocompetent adults. The efficacy of VALTREX for the reduction of transmission of genital herpes beyond 8 months in discordant couples has not been established. The efficacy of VALTREX for the reduction of transmission of genital herpes in individuals with multiple partners and nonheterosexual couples has not been established. Safer sex practices should be used with suppressive therapy (see current Centers for Disease Control and Prevention  Sexually Transmitted Diseases Treatment Guidelines).
Herpes zoster: VALTREX is indicated for the treatment of herpes zoster (shingles) in immunocompetent adults. The efficacy of VALTREX when initiated more than 72 hours after the onset of rash and the efficacy and safety of VALTREX for treatment of disseminated herpes zoster have not been established.

## Pediatric Patients
Cold Sores (Herpes Labialis): VALTREX is indicated for the treatment of cold sores (herpes labialis) in pediatric patients aged greater than or equal to 12 years. The efficacy of VALTREX initiated after the development of clinical signs of a cold sore (e.g., papule, vesicle, or ulcer) has not been established.
Chickenpox: VALTREX is indicated for the treatment of chickenpox in immunocompetent pediatric patients aged 2 to less than 18 years. Based on efficacy data from clinical trials with oral acyclovir, treatment with VALTREX should be initiated within 24 hours after the onset of rash .

## Limitations of Use
The efficacy and safety of VALTREX have not been established in:
- Immunocompromised patients other than for the suppression of genital herpes in HIV-1infected patients with a CD4+ cell count greater than or equal to 100 cells/mm3.
- Patients aged less than 12 years with cold sores (herpes labialis).
- Patients aged less than 2 years or greater than or equal to 18 years with chickenpox.
- Patients aged less than 18 years with genital herpes.
- Patients aged less than 18 years with herpes zoster.
- Neonates and infants as suppressive therapy following neonatal herpes simplex virus (HSV) infection.
Valproate sodium contraindications

# Contraindications
Depacon should not be administered to patients with hepatic disease or significant hepatic dysfunction .
Depacon is contraindicated in patients known to have mitochondrial disorders caused by mutations in mitochondrial DNA polymerase  (POLG; e.g., Alpers-Huttenlocher Syndrome) and children under two years of age who are suspected of having a POLG-related disorder .
Depacon is contraindicated in patients with known hypersensitivity to the drug .
Depacon is contraindicated in patients with known urea cycle disorders .
Venlafaxine nonclinical toxicology

# Nonclinical Toxicology

## Carcinogenesis, Mutagenesis, Impairment of Fertility

### Carcinogenesis
Venlafaxine was given by oral gavage to mice for 18 months at doses up to 120 mg/kg per day, which was 1.7 times the maximum recommended human dose on a mg/m2basis. Venlafaxine was also given to rats by oral gavage for 24 months at doses up to 120 mg/kg per day. In rats receiving the 120 mg/kg dose, plasma concentrations of venlafaxine at necropsy were 1 times (male rats) and 6 times (female rats) the plasma concentrations of patients receiving the maximum recommended human dose. Plasma levels of the O-desmethyl metabolite were lower in rats than in patients receiving the maximum recommended dose. Tumors were not increased by venlafaxine treatment in mice or rats.

### Mutagenesis
Venlafaxine and the major human metabolite, O-desmethylvenlafaxine (ODV), were not mutagenic in the Ames reverse mutation assay in Salmonella bacteria or the Chinese hamster ovary/HGPRT mammalian cell forward gene mutation assay. Venlafaxine was also not mutagenic or clastogenic in the in vitro BALB/c-3T3 mouse cell transformation assay, the sister chromatid exchange assay in cultured Chinese hamster ovary cells, or in the in vivo chromosomal aberration assay in rat bone marrow. ODV was not clastogenic in the in vitro Chinese hamster ovary cell chromosomal aberration assay, but elicited a clastogenic response in the in vivo chromosomal aberration assay in rat bone marrow.

### Impairment of Fertility
Reproduction and fertility studies of venlafaxine in rats showed no adverse effects on male or female fertility at oral doses of up to 2 times the maximum recommended human dose of 225 mg/day on a mg/m2 basis.
However, reduced fertility was observed in a study in which male and female rats were treated with O-desmethylvenlafaxine (ODV), the major human metabolite of venlafaxine, prior to and during mating and gestation. This occurred at an ODV exposure (AUC) approximately 2 to 3 times that associated with a human venlafaxine dose of 225 mg/day.
Ventricular septal defect overview

# Overview
A ventricular septal defect (or VSD) is a defect in the ventricular septum (the wall dividing the left and right ventricles of the heart). The ventricular septum consists of a muscular (inferior) and membranous portion (superior). The membranous portion (which is close to the atrioventricular node) is most commonly affected.
Congential VSDs are collectively the most common congenital heart defect. The incidence of VSD in adulthood has decreased over past decades due to successful surgical closure of large defects.

# Epidemiology and Demographics
The ventricular septal defect is the most common congenital cardiac malformation with an incidence of 300 to 350 per 100,000 live births, corresponding to 30% of all newborns with a congenital heart defect. There is no predilection based on sex. Incidence rates are similar in different races and seasons and are unrelated to maternal age, birth order, sex, and socioeconomic status. Congential VSDs are frequently associated with other congenital conditions, such as Down syndrome. 

# Diagnosis

## Physical Examination
The physical examination findings of a ventricular septal defect depend upon the size of the defect, the location of the defect, the magnitude and directionality of the intracardiac shunt, and the age of the patient (the duration of the VSD).

## CT
Computed tomography can be helpful as a diagnostic tool in conditions where the echocardiographic findings are inconclusive.

## MRI
Magnetic resonance imaging can be helpful as a diagnostic tool in conditions where the echocardiographic findings are inconclusive.
Virilization (patient information)
For the WikiDoc page for this topic, click here

# Overview
Virilization is when a female develops male sex characteristics, or a newborn boy has increased male characteristics at birth.

# What causes Virilization?
- Virilization may be caused by:
- Excess testosterone production
- Use of anabolic steroids
- In newborn girls, the condition may be caused by:
- Certain medications taken by the mother during pregnancy
- Congenital adrenal hyperplasia in the baby or her mother
- Other medical conditions in the mother (such as tumors of the ovaries or adrenal glands that release male hormones)

# Diagnosis
Signs of virilization in a female may include:
- Deepening of the voice
- Facial hair
- Increase in body hair
- Male-pattern baldness
- Swelling of the clitoris

# Treatment options
Tests may include:
- Blood tests to detect excess testosterone in females
- CT scan, MRI, or ultrasound to rule out tumors of the ovaries and adrenal glands

# Where to find medical care for Virilization?
Directions to Hospitals Treating Virilization

# Source
Zolmitriptan indications and usage

# Indications and Usage
Zolmitriptan orally disintegrating tabletsare indicated for the acute treatment of migraine with or without aura in adults.

### Limitations of Use
- Only use zolmitriptan orally disintegrating tablets if a clear diagnosis of migraine has been established. If a patient has no response to zolmitriptan orally disintegrating tablets treatment for the first migraine attack, reconsider the diagnosis of migraine before zolmitriptan orally disintegrating tablets are administered to treat any subsequent attacks.
- Zolmitriptan orally disintegrating tablets are not indicated for the prevention of migraine attacks.
- Safety and effectiveness of zolmitriptan orally disintegrating tablets have not been established for cluster headache.
2,5-Dimethoxy-4-methylamphetamine

# Overview
DOM (or STP, allegedly standing for Serenity, Tranquillity and Peace, but based on the name of STP (motor oil company) and thus named by Owsley Stanley) is a psychedelic hallucinogenic drug and a substituted amphetamine of the phenethylamine class of compounds, sometimes used as an entheogen. DOM was first synthesized by Alexander Shulgin. The full name of the chemical is 4-methyl-2,5-dimethoxyamphetamine. DOM has a stereocenter and R-(-)-DOM is the more active stereoisomer. In his book PIHKAL (Phenethylamines I Have Known and Loved), Shulgin lists the dosage range as 3 to 10 mg. DOM is generally taken orally.  DOM is classified as a Schedule I substance in the United States, and is similarly controlled in other parts of the world. Internationally, DOM is a Schedule I drug under the Convention on Psychotropic Substances.
Not much information is known about the toxicity of DOM.  According to Shulgin, the effects of DOM typically last 14 to 20 hours.  Clinical studies have indicated that repeated exposures to DOM can result in the rapid development of tolerance in as little as three days.
In mid-1967, tablets containing 20mg (later 10mg) of DOM were widely distributed in the Haight-Ashbury District of San Francisco under the name of STP.  This short-lived appearance of DOM on the black market proved disastrous for several reasons.  First, the tablets contained an excessively high dose of the chemical.  This, combined with DOMs slow onset of action (which encouraged some users, familiar with drugs that have quicker onsets, such as LSD, to re-dose) and its remarkably long duration, caused many users to panic and sent some to the emergency room.  Second, treatment of such overdoses was complicated by the fact that no one at the time knew that the tablets called STP were, in fact, DOM.
Another structural isomer of DOM is also known to be active. This compound has the methoxy groups at the 2,6 positions instead, and is known as -DOM.
4-Chloro-2,5-dimethoxyamphetamine

# Overview
4-Chloro-2,5-dimethoxyamphetamine or 2,5-dimethoxy-4-chloroamphetamine  or 4-Chloro-2,5-DMA or DOC is a psychedelic hallucinogenic drug of the phenethylamine family.  Used by some as an entheogen, DOC was presumably first synthesized by Alexander Shulgin.  The drug is generally taken orally, but some users have been known to insufflate or smoke the pure powder.

# Chemistry
DOC is a substituted alpha-methylated phenethylamine, a class of compounds commonly known as amphetamines.  The full name of the chemical is 2,5-dimethoxy-4-chloro-amphetamine. DOC has a stereocenter and R-(-)-DOC is the more active stereoisomer.  DOC is the 3-carbon chain homologue of the psychedelic 2C-C.

# Dosage
A normal average dose of DOC ranges from .5-8.0 mg; the former producing threshold effects, and the latter producing extremely strong effects. Doses up to 10mg have been known to send the user into a restless stupor. Onset of the drug is 1-3 hours, peak and plateau at 4-8 hours, and a gradual come down. After effects can last well into the next day.

# Effects
Unlike simple amphetamines, DOC is a psychedelic that resembles LSD, DOB, and mescaline.  These effects include open and closed eye visuals, increased awareness of sound and movement and euphoria.

# Pharmacology
The mechanism of DOCs hallucinogenic effects is unknown, but like DOB and DOI, it may be mediated by partial agonistic activity at the 5-HT2A serotonin receptor, and binding affinity for the 5-HT2B and the 5-HT2C serotonin receptor.

# Dangers
The toxicity of DOC is not known, but nausea, chest pains, and vasoconstriction have been reported by some users.  In June 2006 four teenagers were admitted to a hospital in Metropolitan Detroit, Michigan after accidentally overdosing DOC.  To date, there have been no deaths attributed to DOC.  However, DOC is an extremely potent psychoactive, and the risk of overdose is great if unknown or extreme dosages are taken.

# Popularity
Although rare on the black market, sales of DOC on blotting paper and in capsules was reported in late 2005.  DOC is sometimes misrepresented as LSD by unscrupulous dealers.  This is particularly dangerous, as DOC is not known to have the safety profile of LSD.

# Legality
4-chloro-2,5-dimethoxyamphetamine is unscheduled in the United States. It is likely that it would be considered an analogue (of DOB or DOM), in which case, sales for human consumption or possession with the intent to ingest could be prosecuted under the Federal Analogue Act. In the United States, the analogues 2,5-dimethoxyamphetamine, 4-bromo-2,5-dimethoxyamphetamine, and 4-methyl-2,5-dimethoxyamphetamine are Schedule I controlled substances.  DOC is scheduled in many other countries including Canada, Germany, New Zealand, Sweden and the UK.
5-lipoxygenase-activating protein
Arachidonate 5-lipoxygenase-activating protein also known as 5-lipoxygenase activating protein, or FLAP, is a protein that in humans is encoded by the ALOX5AP gene.

# Function
FLAP is necessary for the activation of 5-lipoxygenase and therefore for the production of leukotrienes, 5-hydroxyeicosatetraenoic acid, 5-oxo-eicosatetraenoic acid, and specialized pro-resolving mediators of the lipoxin and resolvin classes.  It is an integral protein within the nuclear membrane.  FLAP is necessary in synthesis of leukotriene, which are lipid mediators of inflammation that is involved in respiratory and cardiovascular diseases. FLAP functions as a membrane anchor for 5-lipooxygenase and as an amine acid-bind protein. How FLAP activates 5-lipooxygenase is not completely understood, but there is a physical interaction between the two. FLAP structure consist of 4 transmembrane alpha helices, but they are found in 3s( trimer) forming a barrel. The barrel is about 60 A high and 36 A wide.

# Clinical significance
Gene polymorphisms in FLAP are suspected of playing a role in Alzheimer's disease. Leukotrienes, which need the FLAP protein to be made, have an established pathological role in allergic and respiratory diseases. Animal and human genetic evidence suggests they may also have an important role in atherosclerosis, myocardial infarction, and stroke. The structure of FLAP provides a tool for the development of novel therapies for respiratory and cardiovascular diseases and for the design of focused experiments to probe the cell biology of FLAP and its role in leukotriene biosynthesis.

# Inhibitors
- AM-679
ALS Therapy Development Institute
The ALS Therapy Development Institute (ALS TDI) is a nonprofit biotechnology company seeking effective treatments for amyotrophic lateral sclerosis (ALS). ALS TDF was founded in 1999 by James Heywood and Robert Bonazoli after James' brother, Stephen Heywood, was diagnosed with the disease. In 2007, ALS TDF changed its name to ALS TDI corresponding with a major grant and research partnership with the MDA's Augie's Quest.
ALS, also known as Lou Gehrigs disease, is a neurodegenerative disorder that paralyzes the body but leaves the mind intact.  ALS is not rare; 350,000 patients have it worldwide.  Patients live on average two-to-five years following diagnosis. There is no cure and no effective treatment.
TDI practices open-source science and maintains a patient and research-focused discussion forum at www.als.net. ALS TDI is a federal registered 501c3 non-profit organization, all donations go directly to fund research and are considered tax-deductible.