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>>> What are the types of pharmaceutical patents?
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174660912
https://synapse.patsnap.com/blog/what-are-the-types-of-pharmaceutical-patents
There are several different types of pharmaceutical patents that can be granted. Some of the most common include:
Product patents: These patents protect the chemical structure or genetic sequences of a drug.
Usage/Method patents: Also known as method-of-use patents, these patents cover the use of a particular compound to treat a specific disease or condition or new ways of using an existing drug to treat a specific disease or condition. They provide exclusivity for the drug's use in treating certain illnesses.
Composition patents: These patents protect the main active ingredients in a formulation.
Formulation/composition patents: These patents protect the way a drug is formulated and administered. For example, they may cover the dosage form, route of administration, or delivery system used for a medication.
Process patents: These patents cover the manufacturing process for a drug. They may protect the methods used to synthesize the active ingredient or prepare the final product.
Combination patents: These patents cover combinations of two or more active ingredients. They may protect the use of multiple drugs together to treat a specific disease or condition.
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>>> Anavex Life Sciences to Present at the H.C. Wainwright 5th Annual Neuro Perspectives Virtual Conference
Anavex Life Sciences Corp.
Jun 20, 2024
https://finance.yahoo.com/news/anavex-life-sciences-present-h-113000764.html
NEW YORK, June 20, 2024 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative, neurodevelopmental and neuropsychiatric disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, schizophrenia, and other central nervous system (CNS) diseases, today announced that Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex, will present at the H.C. Wainwright 5th Annual Neuro Perspectives Virtual Conference being held June 27, 2024.
An audio webcast will be accessible on demand beginning on Thursday, June 27, 2024, at 7:00 a.m. ET through the Investors section of the Company’s website at www.anavex.com.
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative, neurodevelopmental, and neuropsychiatric disorders, including Alzheimer's disease, Parkinson's disease, Rett syndrome, schizophrenia and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients and one Phase 2/3 in pediatric patients with Rett syndrome.
ANAVEX®2-73 is an orally available drug candidate that restores cellular homeostasis by targeting SIGMAR1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease.
We believe that ANAVEX®3-71, which targets SIGMAR1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn.
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>>> Anavex Life Sciences Corp. AVXL), a clinical stage biopharmaceutical company, engages in the development of therapeutics for the treatment of central nervous system diseases.
Its lead product candidate is ANAVEX 2-73 for the treatment of Alzheimer's disease and Parkinson's disease, as well as other central nervous system diseases, including rare diseases, such as Rett syndrome, a rare severe neurological monogenic disorder; and infantile spasms, Fragile X syndrome, and Angelman syndrome.
The company's drug candidate also comprises ANAVEX 3-71, which is in clinical trial for the treatment of schizophrenia, frontotemporal dementia, and Alzheimer's disease.
Its preclinical drug candidates include ANAVEX 1-41 for the treatment of depression, stroke, and neurogenerative disease; ANAVEX 1066 for the potential treatment of neuropathic and visceral pain; and ANAVEX 1037 to treat prostate and pancreatic cancer. The company was incorporated in 2004 and is headquartered in New York, New York.
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https://finance.yahoo.com/quote/AVXL/profile/
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>>> Damage to synapses caused by Alzheimer’s disease reversed
A novel treatment has been proven to effectively treat cognitive decline in mice with Alzheimer’s disease.
OIST - Okinawa Institute of Science and Technology
June 20, 2024
https://www.oist.jp/news-center/news/2024/6/20/damage-synapses-caused-alzheimers-disease-reversed
Alzheimer’s disease is a progressive, neurodegenerative disorder that is the leading cause of dementia, which involves cognitive decline, memory loss, and ultimately the inability to perform daily tasks. It affects an estimated 55 million people globally, and in Japan alone, an estimated 4.4 million people are living with dementia, a number that is expected to climb to 6.5 million in 2060 according to government data.
Curing or delaying the debilitating symptoms of Alzheimer’s is extraordinarily difficult due to the elusive nature of the disease. The exact cause is unknown, and likely involves multiple factors from genetics to lifestyle, and due to the progressive nature of the condition, it is often too late to treat effectively once the symptoms begin to impact daily life.
However, a team of researchers from the former Cellular and Molecular Synaptic Function Unit at the Okinawa Institute of Science and Technology (OIST), led by Professor Emeritus Tomoyuki Takahashi, has now made headway into finding a viable treatment of those symptoms, putting us on the path to rescuing brain functions before they are irreversibly damaged by Alzheimer’s disease. Their findings have recently been published in Brain Research. “We successfully reversed the symptoms of Alzheimer’s disease in mice,” explains Dr. Chia-Jung Chang, first author of the study and presently a member of the Neural Computation Unit at OIST. “We achieved this with a small, synthetic peptide, PHDP5, that can easily cross the blood-brain barrier to directly target the memory center in the brain.”
Saving dynamin
A central factor in Alzheimer’s disease is the health of brain synapses. Synapses are the junctions between neurons in the brain, where information is conveyed from one neuron to the next through chemical neurotransmitters encased in synaptic vesicles. These vesicles have to be constantly recycled to secure a steady supply, and an essential step in the vesicle recycling process is the membrane retrieval (endocytosis) by the protein dynamin, which ‘cuts off’ the vesicle from the cell membrane. Dynamin is available throughout the neurons, either freely or bound to the microtubules that make up the cytoskeleton of cells.
Vesicle recycling in the presynaptic terminal at one end of a neuron, showing the role of dynamin during the last step of endocytosis (membrane retrieval), where the protein cuts off the vesicle from the cell membrane. The vesicle is then filled with neurotransmitters and transported back to the release site of cell membrane, where the neurotransmitters are released, and the vesicle is recycled.
The key antagonist here is the protein tau, which in normal circumstances is involved in stabilizing the microtubules. However, in the early stage of Alzheimer’s, tau begins to disassociate from microtubules. Being freely available, tau over-assembles new microtubules, effectively vacuuming dynamin from cell, making it unavailable for the last step of endocytosis. As Alzheimer’s progresses, the accumulated tau aggregates into neurofibrillary tangles, which are the hallmark of the disease – by the time these tangles show up on brain scans, it is often too late to treat the disease.
The OIST researchers focused specifically on the dynamin-microtubule interaction, and they have previously proven the positive effects of inhibiting this interaction in vitro using the synthetic peptide PHDP5. Dr. Zacharie Taoufiq, presently in the Synapse Biology Unit at OIST and second author of the paper, explains: "By preventing the interaction between dynamin and microtubules, PHDP5 ensures that dynamin is available for vesicle endocytosis during recycling, which can restore the lost communication between neurons inside the synapses at an early stage.”
Using transgenic mice, the researchers have now shown the same restorative effect in vivo. "We were thrilled to see that PHDP5 significantly rescued learning and memory deficits in the mice,” says Dr. Chang. “This success highlights the potential of targeting the dynamin-microtubule interaction as a therapeutic strategy for Alzheimer's disease."
Some of the main findings from the Alzheimer's paper.
Some of the main findings from the paper. SPHDP5 is a scrambled peptide that has no therapeutic effect, used as a control. A) shows the experimental setup with a Morris Water Maze, whereby a mouse is put in a water bath and trained to find a hidden platform using visual cues. B) are representative illustrations of the swimming paths of the mice towards the hidden platform (dashed white line). C) shows the effect of the intranasal administration of PHDP5 over time – notice how the curves for healthy mice (dashed black line) and transgenic mice treated with PHDP5 (grey line with triangles) are very similar. Credit: Chang et al.
Because PHDP5 inhibits dynamin-microtubule interactions generally, the researchers modified the peptide to include a cell-penetrating peptide, which allows the treatment to be administered through the nasal cavity where the blood-brain barrier is not fully developed, and which is close to the memory center of the brain, the hippocampus. In this way, the peptide would be delivered to the hippocampus at a higher concentration than through other methods of administration, while also minimizing potential side effects elsewhere in the body.
From molecules and mazes to viable treatments
Provided the synapses are treated with PHDP5 at a relatively early stage, the damage caused by the rampant dynamin-microtubule interaction can be reversed to the point that the treated transgenic mice have learning and memory abilities on par with healthy mice. While the peptide cannot cure Alzheimer’s, the inhibition of the dynamin-microtubule interaction delays cognitive decline significantly, to the point where it may not affect healthy people within a normal lifespan.
Emboldened by these results, the research team, now headed by Dr. Taoufiq and composed of specialists from different units across OIST, is continuing their work on the treatment. Dr. Taoufiq, based in the Synapse Biology Unit, is working to improve the peptide itself and the ways in which it functions in vivo. “We want to increase the amount of PHDP5 in the brain to achieve better effects, while minimizing side effects,” as he puts it. Meanwhile, Dr. Chang, based in the Neural Computation Unit, is working to introduce AI in the pursuit of additional and more robust data: “We’re using the different areas of expertise within OIST to improve our research.”
At the same time, the team is working with the OIST Innovation division to move the peptide through the production pipeline. “We want to involve pharmaceutical companies going forward,” explains Dr. Taoufiq. “They have the necessary expertise in pharmacology and the capacity for human trials to turn our peptide into a viable treatment.”
While the journey from research to drug is infamously long, taking an average of 20 years from paper to prescription, the researchers remain highly enthusiastic. As Dr. Chang says, “the coronavirus vaccine showed us that treatments can be rapidly developed, without sacrificing scientific rigor or safety. We don’t expect this to go as quickly, but we know that governments – especially in Japan – want to address Alzheimer’s disease, which is affecting so many people. And now, we have learned that it is possible to effectively reverse cognitive decline if treated at an early stage.”
Comment from OIST Professor Emeritus Tomoyuki Takahashi
While he is now retired from OIST, Prof. Takahashi started the project and ran it until the unit’s closure. “In this study, together with the previous one, we have clarified the pathological significance of dynamin-microtubule (MT) interaction in Alzheimer’s disease (AD), by which synaptic functions are significantly impaired. The dynamin-MT inhibitor PHDP5 rescues synaptic dysfunctions caused by tau accumulation in brain slices and can reverse learning and memory deficits to normal levels in transgenic AD mice models. This in vivo effect is robust since it is reproducible in double-blind tests and consistent in two types of model mice. Clearly, the next crucial step is to submit PHDP5 to the Phase 1-4 tests of AD therapeutic trials, which would be best performed by pharmaceutical companies. We strongly hope that our peptide could go through the tests and reach AD patients without much delay and rescue their cognitive symptoms, which is the primary concern of patients and their families.”
Note
The study began in the Cellular and Molecular Synaptic Function Unit, which was closed in March 2024. Professor Tomoyuki Takahashi designed and directed the whole project and wrote the text of the paper, while group leader Dr. Tetsuya Hori, currently in the Synapse Biology Unit together with Dr. Zacharie Taoufiq, arranged the experimental setups, the animals, and organized collaborations. Dr. Chia-Jung Chang conducted behavioral experiments and Dr. Taoufiq designed and modified the peptides.
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Yes, I am long AVXL - I think they will get approval of both drugs eventually. The recent changes in trial criteria in both the U.S. and the E.U. will be positive for them.
Xena, AVXL moves up though the 50 MA, so with luck the next stop may be the 4.50 area (mid-May high). That bullish setup yesterday was classic. The only thing somewhat lacking in today's move is that it could use a little more volume, but maybe this afternoon.
Not sure if you are long AVXL (?) I don't know much about the company's fundamentals, but was just looking at the chart.
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>>> Sarepta Jumps on Broad Approval for Muscular Dystrophy Drug
Bloomberg
by Gerry Smith
Jun 20, 2024
https://finance.yahoo.com/news/sarepta-jumps-broad-approval-muscular-220459501.html
(Bloomberg) -- Sarepta Therapeutics Inc.’s gene therapy received expanded US approval to include more children with a deadly muscle disease, expanding the market for a controversial treatment that still hasn’t proved its benefit in clinical trials.
Sarepta shares surged 36% in extended trading at 5:51 p.m. in New York.
The drug’s approval was widened for use in patients who are at least 4 years of age with Duchenne muscular dystrophy, Sarepta said in a statement. The agency granted a traditional approval for patients who can still walk. It also granted an accelerated approval for patients who can’t walk, meaning the company will need to perform a confirmatory trial.
The therapy, called Elevidys, has highlighted a type of approval that’s become the center of debate. The treatment, which is priced at $3.2 million, was initially cleared through an accelerated approval pathway, a regulatory shortcut designed to get drugs for devastating diseases to market quickly, often based on preliminary data. If a confirmatory trial doesn’t show the drug provides a clinical benefit, the FDA can pull it from the market. While such fast approvals may help some desperate patients, critics say the system sometimes allows unproven drugs to stay on the market for years.
The FDA initially cleared Elevidys last year to treat 4- and 5-year-olds, the age group that appeared to gain the most benefit in studies. That earlier FDA decision was an attempt to strike a middle ground in response to questions about the treatment’s effectiveness, and Sarepta has been working since to gain clearance for broader use.
In October, Sarepta said its confirmatory trial failed to clearly slow the disease in a yearlong study of 125 young children. But secondary measures of patients’ movement in the trial were positive, according to the drugmaker, and the company filed with US regulators for expanded, full approval.
Duchenne muscular dystrophy primarily occurs in about 1 in 3,500 male births worldwide. Caused by defects in a protein called dystrophin that helps keep muscle cells intact, the disease leads to severe muscle weakening and atrophy. Most patients die in their 20s, though some are living longer thanks to various treatment options, like steroids and other approved treatments that target a certain genetic mutation.
Sarepta sells other drugs for the disease that require regular IV infusions. Gene therapies such as Elevidys, on the other hand, are one-time treatments that can provide long-lasting benefits. Despite being cleared for only a narrow group of children, Elevidys is one of the most successful therapies to hit the market.
In June, a gene therapy from Pfizer Inc. failed to improve motor function in boys with Duchenne, jeopardizing the future of a medicine that could have been a competitor to Sarepta’s treatment.
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>>> Sarepta Therapeutics, Inc. (SRPT), a commercial-stage biopharmaceutical company, focuses on the discovery and development of RNA-targeted therapeutics, gene therapies, and other genetic therapeutic modalities for the treatment of rare diseases.
It offers EXONDYS 51 injection to treat duchenne muscular dystrophy (duchenne) in patients with confirmed mutation of the dystrophin gene that is amenable to exon 51 skipping;
VYONDYS 53 for the treatment of duchenne in patients with confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping;
AMONDYS 45 for the treatment of duchenne in patients with confirmed mutation of the dystrophin gene; and
ELEVIDYS, an adeno-associated virus based gene therapy for the treatment of ambulatory pediatric patients aged 4 through 5 years with duchenne with a confirmed mutation in the duchenne gene.
The company is also developing SRP-5051, a peptide conjugated PMO that binds exon 51 of dystrophin pre-mRNA; and SRP-9003, a limb-girdle muscular dystrophies gene therapy program.
It has collaboration and license agreements with F. Hoffman-La Roche Ltd; Nationwide Children's Hospital; Genevant Sciences; University of Florida; Dyno Therapeutics; Hansa Biopharma; Duke University; Genethon; and StrideBio. The company was incorporated in 1980 and is headquartered in Cambridge, Massachusetts.
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https://finance.yahoo.com/quote/SRPT/profile/
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Xena, Btw, you mentioned eating lots of dairy. If you are still experiencing lung congestion issues, one thing to keep in mind is that dairy is widely known to strongly stimulate mucus production. So something to keep in mind. I used to love milk, yogurt, cheese, but unfortunately it created too much congestion, and I also had a reaction to the casein protein component (face breaks out).
While lactose intolerance exists, Dr. Gundry says it is actually very rare, and what most people are experiencing is a reaction to the casein protein in the dairy product. Casein A-1 type is usually the culprit, with Casein A-2 type dairy being much less of a problem. Casein A-2 is also found in goat milk, sheep milk, buffalo mozzarella, etc.
>>> A1 beta-casein. Milk from breeds of cows that originated in northern Europe is generally high in A1 beta-casein. These breeds include Holstein, Friesian, Ayrshire, and British Shorthorn.
A2 beta-casein. Milk that is high in A2 beta-casein is mainly found in breeds that originated in the Channel Islands and southern France. These include Guernsey, Jersey, Charolais, and Limousin cows <<<
https://www.healthline.com/nutrition/a1-vs-a2-milk#definition
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Xena, The current AVXL chart setup looks poised for a possible bounce up to 4.50. The longer term chart is not so good, but as a short term trade the chart looks interesting. But ultimately the longer term chart is suggesting a return to key support at 2.50. But just a guess, and will depend upon news flow.
I remember Anavex somewhat from years ago. The CNS-neuro-psych subsector has long been considered one of the riskiest areas of biotech. We called these stocks 'widow makers', but occasionally one will find success. I eventually switched to the cancer sector, specifically the 'armed-MAB' space, but ultimately picked the wrong horse -- Immunogen rather than Seattle Genetics (Seagen). Both were eventually acquired, but SGEN had phenomenal success, much better than IMGN's. These days I only follow biotech very loosely. It's still the 'wild west' of investing, and mainly for gunslingers imo.
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I totally agree... I pray for my nieces and their babies...
Xena, Yes, it looks like AI will be huge. I sold my tech stocks like NVDA, SMCI, AVGO a little early (in favor of the S+P 500), but still had some nice gains. SMCI was a quick double, so can't complain too much, although It wasn't a very big position.
The biggest gain I ever had was in the bio sector years ago, when Dendreon had a big zoom and I picked up a quick 40 K. But unfortunately I managed to lose much of that gain on some subsequent mistakes. These days, being retired I'm very conservative, though still enjoy following the more exciting sectors out of general interest. Concerning AI, to me the whole thing seems ominous since it can facilitate Orwell's 1984. Technology is a double edged sword, and humans are unfortunately not suited for such enhanced power.
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Actually I have facial issues too... lots of noise on the right side.
Did you see my post about Elon's plans on the LWLG board?
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174627440
Xena, It sure is perplexing, like 'a riddle, wrapped in a mystery, inside an enigma'. Sorry I can't be of more help. It doesn't sound like you have Trigeminal Neuralgia though, since that generally involves facial pain
Btw, looks like the June 15 short data for LWLG isn't out yet, but I'm curious to see if there has been a decrease in shares short. The stock's big recent bounce sure looked like short covering. Fwiw, I'll predict that by the June 30 reading, the shares short will have dropped from 17 mil to 15 mil shares. Just a guess though. That last press release reaffirmed the commercialization timeline, and it sounds like a new deal / partnership announcement could be in the offing, which would explain the big 50% rebound in the stock --> ie short covering ahead of the announcement.
>>> Lightwave Logic Reaffirms Commercialization Timeline Presented at the 2024 Annual Shareholder Meeting
PR Newswire
Mon, Jun 3, 2024
https://finance.yahoo.com/news/lightwave-logic-reaffirms-commercialization-timeline-123100244.html
>> company continues to diligently pursue commercial material supply licensing agreements in 2024 and expects the cadence to grow in 2025 and beyond <<
>> accelerated the industry interest in Lightwave Logic's solution which has grown to over 25 companies to date <<
>> focus on Tier 1 material supply licensing agreements as well as having our polymer high-speed modulators evaluated by fiber optic communication companies. Our team continues to work tirelessly to realize near-term commercial agreement goals for 2024, 2025, and beyond <<
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Xena, >>> If I stop taking supplements for 6-8 hours I lose functional response...If I don't take enough NAC I feel it immediately. <<<
That's because without food, your body is using the cysteine amino acid in NAC as a main (only) food source, since there are no other nutrients coming in. It's basically like long term fasting, and you start burning fat, producing ketones, which can taste and smell real bad. Your saliva is probably full of ketones, which is what you taste when you try to eat something.
That sounds like what could be happening. If so, the solution would be to eat whatever types of food you can handle (or maybe in smoothie form?) which will get you out of ketosis, which will remove the bad taste (ketones), and thus enable you to eat all types of food again.
Sounds logical anyway. I would try eating something starchy first, simple carbs, which will quickly provide the glucose needed and get you out of ketosis. Once out of ketosis, the bad ketone taste fades, and you're back in business. Worth a try anyway, but bottom line is that to live, you obviously have to be able to eat.
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If I stop taking supplements for 6-8 hours I lose functional response...
If I don't take enough NAC I feel it immediately. I always have a stash in my purse.
It is possible that my loss of taste is both neurological and collagen related.
From AI -
Xena, The Cipro may have been the cause. It sounds like Cipro induced taste changes generally don't last too long, but with Covid's effects thrown into the mix, it may be a possibility -
>>> 4. Taste changes
Ciprofloxacin has been associated with loss of taste or a bad taste in the mouth. It’s not dangerous, but it can be unpleasant. Any taste changes should go away after stopping ciprofloxacin. Still, let your provider know if it’s bothering you. You can also work with a dietitian to make food more appealing by experimenting with texture and color.
https://www.goodrx.com/ciprofloxacin/common-side-effects#taste-changes
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Just curious if you are still taking the large NAC doses each day? If so, that's another possibility. I would probably experiment and not take any supplements of any type for a week and see if there is any change. Best to do a full review of everything you are taking --> supplements, prescription meds, etc.
Also look for any chronic chemical exposure. You might have a rare hypersensitivity to something in your indoor or local outdoor environment (or water). For example, if you live near farmland, the chemicals they periodically spray could be a possibility. Farm workers and people living near farms have been getting all kinds of health problems in recent years.
Sounds like a real 'puzzler', but the first step imo would be to stop taking all supplements for a week and see if there is an improvement.
>>> What causes taste disorders?
https://www.nidcd.nih.gov/health/taste-disorders#:~:text=The%20most%20common%20taste%20disorder,GYOO%2Dzee%2Da%5D.
Some people are born with taste disorders, but most develop them after an injury or illness. Among the causes of taste problems are:
- Upper respiratory and middle ear infections
- Radiation therapy for cancers of the head and neck
- Exposure to certain chemicals, such as insecticides and some medications, including some common antibiotics and antihistamines
- Head injury
- Some surgeries to the ear, nose, and throat (such as middle ear surgery) or extraction of the third molar (wisdom tooth)
- Poor oral hygiene and dental problems.
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I appreciate your concern...
I ate many of those foods on a regular basis and enjoyed them for decades.
Those same foods make me want to puke now. It isn't "leaky gut"... It's it all tastes like S#IT and I can't get it down and keep it down.
See this paper...
https://www.aan.com/siteassets/home-page/tools-and-resources/academic-neurologist--researchers/program-director-tools/16tasteandsmell_tr.pdf
Xena, Btw, here's a link to the 'Food as Medicine' board, and in the I-Box section I updated my own daily food and supplement regimen. Still a work in progress, but suggestions are welcome :o) Since you aren't eating well these days, trying some of these foods might help. Between the probiotic, the absence of lectin containing foods, and the absence of glyphosate/Roundup, it should at least improve / reverse any 'leaky gut' that you have. From Gundry's experience, once the gut lining is healed / sealed, most health problems reverse / resolve, as confirmed in the patient's symptoms and blood tests / markers -
https://investorshub.advfn.com/Food-as-Medicine-40084
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Xena, Yes, NAC looks like an interesting all around supplement, I'll check it out. As with everything else in life, probably best to not overdo it too much, since these biological pathways are complex and overlapping. The mucolytic aspect is intriguing since I tend to have some chronic congestion, and I see NAC is FDA approved for that indication (1963). Thanks for the heads up on NAC :o) It sure helped you through the respiratory problems you had with Covid. Here's some additional info on NAC -
>>> What are the Health Benefits of NAC (N-Acetyl Cysteine)?
Healthline
Medically reviewed by Ami Patel PharmD, BCPS
Written by Amy Goodson, MS, RD, CSSD, LD
Updated on January 12, 2024
https://www.healthline.com/nutrition/nac-benefits
FAQs
N-acetyl cysteine (NAC) is a supplement form of cysteine, a conditionally essential amino acid. NAC has many health benefits, including replenishing antioxidants and nourishing your brain.
NAC is considered ‘conditionally essential’ because your body can produce it from other amino acids. It becomes essential only when the dietary intake of methionine and serine is low.
Cysteine is found in most high protein foods, such as chicken, turkey, yogurt, cheese, eggs, sunflower seeds, and legumes.
Consuming adequate cysteine and NAC is important for various health reasons, including replenishing the most potent antioxidant in your body, glutathione. These amino acids also help with chronic respiratory conditions, fertility, and brain health.
Here are the top 9 health benefits of NAC.
1. Essential for making the powerful antioxidant glutathione
NAC is valued primarily for its role in antioxidant production. Along with two other amino acids — glutamine and glycine — NAC is necessary to make and replenish glutathione.
Glutathione is one of your body’s most important antioxidants — compounds that help neutralize free radicals that can damage cells and tissues. Antioxidants help support the body’s natural immune system and toxin-elimination processes. Research also suggests that antioxidant intake can reduce the risk of several chronic conditions, including cardiovascular disease.
SUMMARY
NAC helps replenish glutathione, arguably your body’s most powerful antioxidant. Therefore, it may help improve a variety of health conditions.
2. Helps with detoxification to prevent or diminish kidney and liver damage
NAC plays an important role in your body’s detoxification process. It can help prevent side effects of environmental toxin exposure (3).
Doctors regularly give intravenous NAC to people with an acetaminophen overdose to prevent or reduce kidney and liver damage (4Trusted Source). NAC has applications for other liver diseases thanks to its antioxidant and anti-inflammatory benefits.
SUMMARY
NAC helps detoxify your body and can treat acetaminophen overdoses.
3. May improve mental health conditions and substance use disorder
NAC helps regulate glutamate levels, the brain’s most important neurotransmitter. While glutamate is required for regular brain activity, excess glutamate and glutathione depletion can cause brain damage.
This may contribute to mental health conditions such as bipolar disorder, schizophrenia, obsessive-compulsive disorder (OCD), and substance use disorder (5Trusted Source, 6, 7).
For people with bipolar disorder and depression, NAC may help decrease symptoms and improve quality of life. Moreover, research suggests that it may play a role in treating moderate to severe OCD (8Trusted Source, 9Trusted Source).
Likewise, an animal study suggested that NAC may minimize the adverse effects of schizophrenia, such as social withdrawal, apathy, and reduced attention spans (10Trusted Source).
NAC may also have applications in managing substance use disorders. For example, preliminary studies show that NAC may decrease cannabis and nicotine use and cravings (11Trusted Source, 12Trusted Source).
SUMMARY
By regulating glutamate levels in your brain, NAC may alleviate symptoms of mental health conditions and reduce substance use and cravings.
4. Helps relieve symptoms of respiratory conditions
NAC can relieve symptoms of respiratory conditions by acting as an antioxidant and expectorant, loosening mucus in your air passageways.
As an antioxidant, NAC helps replenish glutathione levels in your lungs and reduces inflammation in your bronchial tubes and lung tissue.
People with chronic obstructive pulmonary disease (COPD) experience long-term oxidative damage and inflammation of lung tissue, which causes airways to constrict, leading to shortness of breath and coughing.
Some studies suggest that taking NAC supplements can help improve COPD symptoms, exacerbations, and lung decline (13Trusted Source, 14Trusted Source).
People with chronic bronchitis can also benefit from NAC. Bronchitis occurs when the mucous membranes in your lungs’ bronchial passageways become inflamed, swell, and shut off airways to your lungs (15Trusted Source).
By thinning mucus in your bronchial tubes and boosting glutathione levels, NAC may help decrease the severity and frequency of wheezing, coughing, and respiratory attacks.
In addition to relieving COPD and bronchitis, NAC may improve other lung and respiratory tract conditions — such as cystic fibrosis, asthma, and pulmonary fibrosis — as well as symptoms of nasal and sinus congestion due to allergies or infections (16Trusted Source).
SUMMARY
NAC’s antioxidant and expectorant capacity can improve lung function by decreasing inflammation and breaking up mucus.
5. Boosts brain health by regulating glutamate and replenishing glutathione
NAC’s ability to replenish glutathione and regulate brain glutamate levels can boost brain health.
The neurotransmitter glutamate is involved in a broad range of learning, behavior, and memory functions, while the antioxidant glutathione helps reduce brain cell oxidative damage associated with aging.
Because NAC helps regulate glutamate levels and replenish glutathione, it may benefit those with health conditions affecting the brain and memory (4Trusted Source).
Alzheimer’s disease slows down learning and memory capacity. Animal studies suggest that NAC may slow the loss of thinking ability in people with Alzheimer’s disease (5Trusted Source, 17).
Parkinson’s disease is characterized by the deterioration of cells that generate the neurotransmitter dopamine. Both oxidative damage to cells and a decrease in antioxidant ability contribute to this disease.
NAC supplements appear to improve both dopamine function and disease symptoms such as tremors (5Trusted Source).
While NAC may improve brain health, more human research is needed to make firm conclusions.
SUMMARY
By helping replenish the antioxidant glutathione and regulate glutamate, NAC has the potential to treat conditions such as Alzheimer’s disease and Parkinson’s disease.
6. May improve fertility in both men and women
In some cases, NAC has been shown to improve male fertility.
Approximately 15% of all couples trying to conceive are affected by infertility. In almost half of these cases, male infertility is the main contributing factor (18Trusted Source). Many male infertility issues increase when antioxidant levels are insufficient to address free radical formation in the reproductive system (19Trusted Source).
One condition contributing to male infertility is varicocele — when veins inside the scrotum enlarge due to free radical damage. In one study, 35 men with varicocele received 600 mg of NAC daily for 3 months after surgery. The combination of surgery and NAC supplementation improved semen integrity and partner pregnancy rate by 22% compared with the control group (20Trusted Source).
In addition, NAC may improve fertility in older women and those with polycystic ovary syndrome (PCOS) by inducing or augmenting the ovulation cycle, although more research is needed (21Trusted Source).
SUMMARY
NAC may help improve fertility in men by reducing oxidative stress that damages or kills reproductive cells. It may also aid fertility in women with PCOS.
7. May stabilize blood sugar by decreasing inflammation in fat cells
High blood sugar and obesity contribute to inflammation in fat tissue.
This can damage or destroy insulin receptors and increase the risk of type 2 diabetes (22Trusted Source).
Animal studies show that NAC may stabilize blood sugar by decreasing inflammation in fat cells and thereby improving insulin resistance (23Trusted Source).
When insulin receptors are intact and healthy, they properly remove sugar from your blood, keeping levels within normal limits.
SUMMARY
By decreasing inflammation in fat tissue, NAC may reduce insulin resistance and improve blood sugar regulation, but human-based research is lacking.
8. May reduce heart disease risk by preventing oxidative damage
Oxidative damage to heart tissue often leads to heart disease, causing strokes, heart attacks, and other severe conditions. NAC may reduce heart disease risk by reducing oxidative damage to tissues in your heart (24Trusted Source).
Studies show that NAC may protect heart function and heart health in people with diabetes and those recovering from certain heart surgeries (25Trusted Source, 26Trusted Source).
SUMMARY
NAC can reduce oxidative damage to your heart, which can, in turn, decrease your risk of heart disease.
9. Ability to boost glutathione levels may improve immune function
NAC and glutathione also benefit immune health.
Research on certain diseases associated with NAC and glutathione deficiency suggests that supplementing with NAC might improve — and potentially restore — immune function (27, 28).
SUMMARY
NAC’s ability to boost glutathione levels may improve immune function.
Dosage
There is no specific dietary recommendation for cysteine because your body can produce small amounts.
For your body to make the amino acid cysteine, you need adequate amounts of folate, vitamin B6, and vitamin B12. These nutrients can be found in beans, lentils, spinach, bananas, salmon, and tuna.
While most protein-rich foods — such as chicken, turkey, yogurt, cheese, eggs, sunflower seeds, and legumes — contain cysteine, some people supplement with NAC to increase their cysteine intake.
NAC has low bioavailability as an oral supplement, meaning your body does not absorb it well. The accepted daily supplement recommendation is 600–1,800 mg of NAC (29).
NAC can be administered intravenously or orally, as an aerosol spray, or in liquid or powder form.
SUMMARY
Eating high protein foods can provide your body with the amino acid cysteine, but you can also take NAC as a supplement to help treat certain conditions.
Side effects
NAC is likely safe for adults when provided as a prescription medication.
However, high amounts may cause nausea, vomiting, diarrhea, and constipation. Inhalation of NAC solutions can cause swelling in the mouth, runny nose, drowsiness, and chest tightness.
People with bleeding disorders or taking blood thinning medications should not take NAC because it may slow blood clotting (30Trusted Source).
NAC has an unpleasant smell that makes it hard to consume. If you choose to take it, consult your doctor first.
SUMMARY
While NAC is considered safe as a prescription medication, it can cause nausea, vomiting, and gastrointestinal disturbances, as well as mouth issues if inhaled.
Frequently asked questions
What is the benefit of taking NAC?
At a glance, supplementing with NAC may help:
replenish glutathione, an important antioxidant
detox your body
treat overdoses of acetaminophen
regulate glutamate, a neurotransmitter involved in mood regulation
relieve respiratory symptoms
support cognitive functions like memory and learning
reduce inflammation
support sugar regulation and reduce insulin resistance
protect heart function
improve your immune system
What happens if you take NAC daily?
You may take NAC daily for a short time, but research about the safety of taking NAC every day for the long term is limited. A 2021 literature reviewTrusted Source found that most studies use it with specific therapeutic goals between 6 weeks and 6 months. Toxicity from NAC intake is rare, particularly in low doses.
If you take NAC to manage or prevent a condition, consider asking a healthcare professional about the best protocol for your health needs.
Does NAC reduce inflammation?
Yes, research suggests NAC suppresses the production of inflammatory compounds in the body.
Doctors may use NAC supplementation as an anti-inflammatory agentTrusted Source in conditions like liver disease, neurodegenerative conditions, mental health disorders (like Alzheimer’s), and heart disease, among others.
Should you take NAC in the morning or at night?
Your healthcare professional may advise when and how often to take NAC depending on your health goals and total dosage.
NAC may also interact with medications and other supplements, so when you should take NAC may depend on your overall protocol.
The bottom line
NAC plays several important roles in human health.
Renowned for its ability to replenish levels of the antioxidant glutathione, it also regulates the important neurotransmitter glutamate. Additionally, NAC helps your body’s detoxification system.
These functions make NAC supplements a viable treatment option for multiple health conditions.
Consult your doctor to determine whether NAC may benefit your health.
<<<
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Ever heard the meme that prevention is the best cure?
This is the point I'm trying to make...
Using NAC before the problem becomes chronic, at the first sign of dysbiosis could prevent the occurrence of C-difficile.
Xena, It turns out the best C-Dif treatment is a fecal transplant, where they re-introduce healthy microbiome bacteria directly back into the patient's GI tract. It works great, but is currently reserved as the last treatment option. But as long as we are bombarded by antibiotics in healthcare, and antibiotic-like compounds in our foods, this problem will never end.
Using antibiotics like Vancomycin against C-Dif will usually work initially, but because Vanc wipes out the entire gut microbiome, the C-Dif infection often recurs. The new Acurx (ACXP) antibiotic has the advantage of being less broad spectrum -- it hits the C-Dif but largely spares the healthy microbiome, and thus avoids the recurrence. We'll see what the Phase 3s show.
But you are right --> it's a$$ backward to treat antibiotic resistance with more antibiotics. The problem is they've been creating this problem for so many decades, and now the food antibiotic side is adding to the problem. Gundry has been all over this problem for years, with published papers and numerous books, and the GI doc / community is finally listening.
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Xena, >> SINT <<
Thanks, those new materials do sound interesting. It looks like the company hasn't gotten much traction so far, but bio-material research is a very interesting area. My nephew is a biomedical engineer (Cook Medical), and my dad was an aeronautical engineer whose satellite work involved many advanced materials (satellite capsule re-entry). On the bio-materials side, I always wondered about these titanium based implants having long term toxicity, and it looks like a link to cancer is now emerging.
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I disagree - if it's caused by antibiotics, treating it with more antibiotics (described as S.O.C. in most of the literature I found) seems like a dumb idea.
I read it again... it sounds like a more reasonable treatment method.
Xena, What the AI search brings up are any data 'overlaps' between the two topics -- NAC and C-Dif. If you searched for 'Vit-C' and 'C-Dif' you would probably also get a bunch of overlaps. Likewise for 'chocolate' and 'C-Dif'.
Our messed up gut microbiome is the underlying problem, originally caused by the widespread use of broad spectrum antibiotics. For many decades docs would hand out antibiotics like candy. Then came the use of glyphosate / Roundup herbicide on crops, which also acts as an antibiotic and kills off our healthy gut bacteria. Glyphosate was originally patented by Monsanto as an antibiotic. It is chemically related to the Agent Orange defoliant used in the Vietnam War to wipe out jungle vegetation. It blocks the 'Shikimate pathway' to kill weeds, but unfortunately our intestinal bacteria also use that same Shikimate pathway. So our conventionally grown food is laden with a broad spectrum antibiotic.
The widely used sweetener sucralose / Splenda also acts as an antibiotic in the gut, and is found in many processed foods including bread, since it is cheaper than sugar. As with aspartame sweetener, sucralose is allowed to be in foods without being included on the label, so it's found in almost everything. Dr. Gundry quotes studies that show that even a half packet of Splenda can have a major negative effect on the gut microbiome.
Anyway, C-Diff is a problem of our own making.
---
Thought you might have in interest in this - see bottom of post..
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174606718
Not recommended as an investment - see its track record of reverse splits.
On that same topic - why isn't NAC being used for C-Difficile?
AI response to "c-difficile "NAC"" search:
Xena, Btw, on the topic of antibiotics, here's a bio stock I've been following loosely since last year (below). They have a new class of antibiotics targeting C-Difficile infections, with Phase 3 to begin in Q4. Looks interesting, and hopefully a significant improvement since it spares the broader microbiome and therefore should prevent recurrence. No position currently, but I traded it a few times in the past. The poster 'Bigworld' is a hospital pharmacist and is also following the stock -
>>> Q1 2024 Acurx Pharmaceuticals Inc Earnings Call <<<
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174464923
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Xena, Yep, probably the Cipro. Best to avoid all prescription meds if possible.
>>> 10 Ciprofloxacin Side Effects You Should Know About
https://www.goodrx.com/ciprofloxacin/common-side-effects
4. Taste changes
Ciprofloxacin has been associated with loss of taste or a bad taste in the mouth. It’s not dangerous, but it can be unpleasant.
Any taste changes should go away after stopping ciprofloxacin. Still, let your provider know if it’s bothering you. You can also work with a dietitian to make food more appealing by experimenting with texture and color.
<<<
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I started losing it after the 2/18 flouroquinolone exposure, and when I got COVID it was BUH-BYE...
Chocolate doesn't even taste right.
I had my own jewelry wholesale business but lost it when I got sick.
Xena, Have you been able to figure out what caused the changes to your sense of taste? Have you had it for a long time, was it related to an illness or medication, etc? Vitamin deficiencies can reportedly cause changes in taste perception, as can some supplements. Try to figure out when it began and what might be the culprit. Covid usually has the opposite effect, but apparently can also cause food to taste metallic.
Btw, you mentioned going to the 'Tucson gem and mineral show'. Just curious if you are a collector? I have a sizable mineral collection, and considered going into Geology as a youth. Also did some rock tumbling / polishing as a kid, and in later years put together a nice size gem collection. I eventually sold the gems, but kept all the minerals and built display cases for them. Once Ebay appeared it was easy to obtain super nice specimens, but also got some great ones when visiting Mt Aetna in Sicily, and also Mt Vesuvius near Naples.
Not to be 'nosy', but you are one of the few females here on I-Hub, and it is refreshing :o)
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When it tastes like S#IT it's hard to eat...
... and that's how most things taste now. I have a narrow selection of tolerable foods.
I used to be an excellent cook, ate lots of salads and veggies.. but now I can't stand them.
Xena, >> barely eat <<
Yikes. Well there's your problem. Good nutrition is absolutely essential to good health. You can't have one without the other. Supplements are merely co-factors that your body uses to facilitate the many chemical reactions. The body can't live without the nutrients themselves --> fats, protein, carbs, and these we only get from food.
Check out Gundry's info. The first step is to avoid processed junk, and he explains what is healthy and what isn't, and why. Once you set up your eating regimen, good health will follow. Just look at Gundry -- he's the picture of health. Many of these so-called nutrition experts look like crap, are emaciated, etc. I saw Gundry and it was obvious that he has cracked the code on nutrition, as evidenced by his own stellar healthiness. Like me he was once 50-60 lbs overweight, and had the usual litany of high BP, autoimmune problems, pre-diabetes, you name it.
As Hippocrates said --> “Let food be thy medicine and medicine be thy food” :o)
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I have a very bad taste disorder, so I barely eat. Supplements keep me going.
My mitochondria are trashed, so supplements keep them going.
Xena, >> NAC <<
I wasn't aware of NAC until you mentioned it a while back, but might give it a try. You have to be careful with individual supplements though. I usually just take a multivitamin and some extra Vit D3 and B-12, plus a probiotic every other day. Also some beet root extract, which helps keep the blood pressure in the 130s or less. I lost over 50 pounds over a period of several years (255 to just under 200) thanks to the Gundry approach, which is a variation on the Mediterranean diet. You drop most grains (wheat, corn, soy) in favor of organic sorghum and millet (which don't have lectins or glyphosate/Roundup), and lots of organic veggies and greens. Beans and lentils are excellent but must be pre-soaked and pressure cooked first (to deactivate the lectins). Meat-wise, Gundry includes fish, though I use organic chicken to avoid the heavy metals found in most fish. With meat, 4 oz per day is plenty, supplemented by 2 organic eggs per day. Gundry stresses healthy fats like olive oil, and an avocado each day. Beef, pork, and bison have a problem -- Neu-5-Gc. See below for more info -
This is exactly what happened to me - two years after the BBX...
The hospital prescribed it improperly and when I wanted to quit the doctor failed and said I couldn't quit...
2/25/18.... the date is irrevocably etched in my brain.
This is what AI says:
Cytochrome P450 -
>>> Pharmacoresistant Severe Mental Health Disorders in Children and Adolescents: Functional Abnormalities of Cytochrome P450 2D6
Front Psychiatry. 2018; 9: 2.
Published online 2018 Jan 24. doi: 10.3389/fpsyt.2018.00002
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810290/
Background
Severe mental health disorders in children and adolescents represent a major public health problem. Despite adequate drug treatment, some patients develop pharmacoresistant disease. As a consequence, physicians are confronted with prescribing challenges, prolonged hospitalization and increased risk of adverse events, thus aggravating short-, medium-, and long-term prognosis. The majority of psychotropic treatments, particularly antipsychotics and antidepressants, are metabolized at hepatic level by cytochrome P450 (CYP), particularly by CYP3A4 and CYP2D6. Several CYP2D6 genetic polymorphisms are described to be associated with ultrarapid (UM) or poor drug metabolism (PM), inducing clinical resistance and/or adverse events, and might therefore be related to pharmacoresistant severe mental health disease.
...Functional anomalies of CYP2D6 concerned more than half of our pediatric inpatient sample with pharmacoresistant disease. However, our case reports are limited by the low sample size. Nevertheless, knowledge of individual metabolism and in particular CYP2D6 genotyping should be considered for clinical workup and therapy adjustment in resistant patients in child and adolescent psychiatry and might permit better treatment outcome, increased treatment adherence and diminished adverse events.
<<<
_______________________
>>> What happens if you are a poor metabolizer of a drug?
If your body metabolizes a drug too slowly, it stays active longer, and may be associated with side effects. Because of this, your doctor may characterize you as being one of four metabolizer types, with respect to a specific enzyme. Poor metabolizers have significantly reduced or non-functional enzyme activity.
<<<
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>>> Anaphylaxis to Ciprofloxacin Requiring Emergent Surgical Cricothyrotomy
Eur J Case Rep Intern Med. 2022; 9(2): 003180.
Published online 2022 Feb 24. doi: 10.12890/2022_003180
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900558/
Wesley Tangcorresponding author and Edwina Rao
Abstract
Although allergies to antibiotics are commonly stated, anaphylactic reactions are uncommonly reported. This is especially the case with reactions to fluoroquinolone antibiotics. Furthermore, airway emergencies are rare. We present a case of ciprofloxacin-induced acute airway obstruction and anaphylaxis, necessitating emergent surgical cricothyrotomy following respiratory distress.
LEARNING POINTS
Anaphylactic reactions to fluoroquinolone antibiotics are extremely rare.
There are currently no standardized diagnostic tests, making the diagnosis of anaphylaxis challenging and largely based on history alone.
Treating clinicians should be aware of this rare, but potentially rapidly fatal adverse drug reaction.
Allergies to antibiotics are common, with roughly 2.2% of all hospitalized patients developing a cutaneous drug reaction[1]. The majority of these reactions are caused by trimethoprim-sulfamethoxazole, amoxicillin, penicillin and ampicillin[2]. Fluoroquinolones are a class of antibiotics with most reactions being mainly mild and affecting the gastrointestinal tract or central nervous system[3]. The estimated prevalence of hypersensitivity reactions to fluoroquinolones of any severity has been estimated to be low at 44 emergency department visits per 100,000 prescriptions in one study in the USA[4]. This same study identified higher rates of moxifloxacin-related hypersensitivity reactions compared with levofloxacin or ciprofloxacin[4]. The authors present an unusual case of a patient who took one dose of oral ciprofloxacin for epididymitis on an outpatient basis. Within 1 hour of ingestion, the patient complained of difficulty speaking, and severe swelling of the eyes, lips and tongue. After failed attempts at endotracheal intubation, an emergent surgical cricothyroidotomy was performed.
...He was continued on epinephrine infusion and was placed on IV steroids and antihistamines. He was not given any further doses of ciprofloxacin and was switched to doxycycline for epididymitis. He was taken to the operating room on hospital day 3 for attempted extubation and underwent pharyngoscopy. However, after evaluation of his airway by Anesthesia and Otorhinolaryngology, it was felt it was unsafe to proceed given the minimal reduction in airway swelling. The patient was subsequently taken back to the operating room on hospital day 5 for high-risk extubation and formal tracheostomy.
...The patient followed up with both Otorhinolaryngology and Pulmonology within 4 weeks of discharge and had experienced no acute issues. He continues to follow up with his PCP and has had no recurrence 6 months after hospital discharge.
exact mechanism of fluoroquinolone allergy has not been clearly defined. Furthermore, there are no standardized diagnostic tests, making the diagnosis challenging and largely based on history alone[5]. Skin testing has been shown to have false-positive results with fluoroquinolones when used in high concentrations[6]. Other studies have shown fluoroquinolones to directly induce histamine release[7]. One other option is the basophil activation test, although this has shown varying testing characteristics with fluoroquinolones with reported sensitivity ranging from 50% to 100%, and specificity from 80% to 100%[8,9]. Finally, if other diagnostic tests or procedures lead to inconclusive results, there is also drug provocation testing. However, drug provocation tests have serious drawbacks as they are often not performed, are time-consuming, require trained personnel in a clinical setting, and may provoke life-threatening reactions[10].
...Drug hypersensitivity reactions to fluoroquinolones are becoming more common due to increasing prevalence and case complexity. One study from 2005–2010 estimated an increase in reported allergy to fluoroquinolones from 0.5% to 6.8% diagnosed by clinical history, skin tests, in vitro tests, and drug provocation testing[11]. In 2016, the United States Food and Drug Administration (US FDA) updated the boxed warning on fluoroquinolones recommending against their use as first-line agents for the routine pharmacological management of uncomplicated urinary tract infections, acute sinusitis and acute bronchitis. Interestingly, and despite the US FDA’s boxed warning, there was no significant change in fluoroquinolone prescription rates before and after the FDA boxed warning[12].
In summary, we report a case of severe anaphylaxis induced by ciprofloxacin necessitating an emergent surgical airway. Clinicians should be aware of this as a rare, but potentially fatal adverse drug reaction.
<<<
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>>> Ciprofloxacin impairs mitochondrial DNA replication initiation through inhibition of Topoisomerase 2
Nucleic Acids Res. 2018 Oct 12; 46(18): 9625–9636.
Published online 2018 Aug 31. doi: 10.1093/nar/gky793
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182158/#:~:text=Ciprofloxacin%20caused%20a%20dramatic%20effect,3A%E2%80%93E%20and%204A).
Anu Hangas,1 Koit Aasumets,2 Nina J Kekäläinen,1 Mika Paloheinä,1 Jaakko L Pohjoismäki,1 Joachim M Gerhold,2 and Steffi Goffart1
ABSTRACT
Maintenance of topological homeostasis is vital for gene expression and genome replication in all organisms. Similar to other circular genomes, also mitochondrial DNA (mtDNA) is known to exist in various different topological forms, although their functional significance remains unknown. We report here that both known type II topoisomerases Top2a and Top2ß are present in mammalian mitochondria, with especially Top2ß regulating the supercoiling state of mtDNA. Loss of Top2ß or its inhibition by ciprofloxacin results in accumulation of positively supercoiled mtDNA, followed by cessation of mitochondrial transcription and replication initiation, causing depletion of mtDNA copy number. These mitochondrial effects block both cell proliferation and differentiation, possibly explaining some of the side effects associated with fluoroquinolone antibiotics. Our results show for the first time the importance of topology for maintenance of mtDNA homeostasis and provide novel insight into the mitochondrial effects of fluoroquinolones.
...The rapid and dose-dependent accumulation of supercoiled mtDNA after ciprofloxacin treatment (Supplementary Figure S3) was more extreme than the changes caused by knockdown of Top2ß
...As ciprofloxacin has been described to have cytostatic effects on some cancer cell lines
...Ciprofloxacin impairs cellular physiology
...Ciprofloxacin caused a dramatic effect on mtDNA topology, blocking replication initiation, reducing copy number and inhibiting mitochondrial transcription (Figures ?(Figures2B,2B, ?,3A3A–E and 4A). Ciprofloxacin, the third most commonly used antibacterial antibiotic, stops the cleavage/re-ligation reaction of type II topoisomerases midway, generating double-strand breaks, persistent protein–DNA adducts and reduces also the overall enzyme activity (30). Its toxicity to mitochondria has been reported in various studies, suggesting a broad range of mechanisms including topoisomerase inhibition, oxidative stress, altered calcium handling and photosensitization
...doxorubicin, another known type II topoisomerase inhibitor
...The severe side effects of ciprofloxacin and other fluoroquinolones include tendinopathies such as tendon rupture, joint inflammation, muscle weakness, central and peripheral neuropathies, epilepsy and psychological symptoms such as depression.
...Ciprofloxacin has also been reported to interfere with physiologically significant cell differentiation processes, such as spermatogenesis (57), brain development (41), bone mineralization (58), as well as to induce renal toxicity and heart arrhythmia
...As fluoroquinolone antibiotics are widely used and effective drugs against a number of important bacterial pathogens, their dosage, systemic enrichment and side-effects should be reviewed in the mitochondrial context, and their clinical use should be considered with great care.
<<<
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Xena, It sounds like an anaphylactic reaction to the Cipro, which may be a totally different phenomenon than FQ poisoning / Fluoroquinolone Associated Toxicity. So you may be barking up the wrong tree in blaming your subsequent health problems on the Cipro.
If your long term health problems are mainly respiratory related, these could be explained as cumulative effects of lung damage from - 1) HCL exposure in school, 2) Coccidioidomycosis infection, and 3) Covid. So the Cipro may have had little / nothing to do with your ongoing respiratory problems. The Coccidioidomycosis infection in particular could have damaged your lungs sufficiently to produce lifelong lung problems. The NAC provides some relief since it breaks up the congestion / mucus.
>> Why are you so curious about this ? <<
It's an interesting 'puzzle', and I also have experienced lung problems from long term exposure to composite dust (dental restorative materials), in the form of pulmonary fibrosis.
---
Basically, my friend knew what was happening before I did and called the ambulance. I went into the bedroom to use the inhaler and went into anaphylaxis. The EMT worked on me on the way to the hospital, but I remember "going home" and being at peace, then being brought back.. I was at the hospital then.
I really only remember bits and pieces. I slept and when I woke up and one of the Docs that brought me back was sitting in a chair in my hospital room.
For all I know it really could have been my second dose.
Why are you so curious about this ????
Xena, >> first dose <<
First we need to establish what caused you to stop breathing. Was it an anaphylactic allergic reaction to the Cipro, or alternately, was it because of the Coccidioidomycosis lung condition? Since "the worst of the Coccidiomycosis was over with", that would leave an anaphylactic reaction to the Cipro.
So summarizing, the doc started you on the oral Cipro, and you took it several times over a 'day or two'? And that's when you stopped breathing? Do you remember if you had swelling of the face / throat? Did the EMT intubate you or give you epinephrine, or CPR?
>> FQ poisoning <<
Did you subsequently develop symptoms like these (below), or have your longer term health issues centered on respiratory problems?
>>> Long-lasting incapacity of Fluoroquinolone Associated Toxicity (FQAT), which is not officially documented yet. This review aimed to précis the existing information on FQA long-term toxicity, such as cardiotoxicity, aortic aneurysm, tendon rupture, nephrotoxicity, hepatotoxicity, peripheral neuropathy, vagus nervous dysfunction, reactive oxygen species (ROS), phototoxicity, glucose hemostasis, and central nervous system (CNS) toxicity. <<<
Thanks for any additional info.
---
I don't remember when I took my first dose, but it was only a day or two at the most. Fortunately I had a friend over for dinner who was an ex EMT - otherwise I probably would have died on my own.
The worst of the Coccidiomycosis was over with, but it was lingering. That's why the Dr wouldn't believe that was the problem. The fact that I inhaled HCL in H.S. chem class didn't help my lungs either. Still, after taking NAC for a long time my lungs were pretty well healed, until I got the FQ poisoning.
Xena, >> My response was - I quit breathing and died <<
Several questions -
1) How long after receiving Cipro did you stop breathing?
2) How severe were your lung symptoms from the Coccidioidomycosis prior to receiving the Cipro?
Thanks.
---
In the late '90s I was given Cipro for a persistent fungal infection - Coccidioidomycosis contracted at the Tucson gem and mineral show. The fool that I had for a doctor told me it as "self limiting" and had changed to a respiratory infection. My response was - I quit breathing and died.
I was resuscitated and it took 8-10 years of supplementation to get over it. That's when I discovered NAC.
I've been 125-135 lbs most of my life, but I gained 100 lbs during that time.
The second was on 2/25/18. It was prescribed at a hospital for a routine UTI. They gave me the first dose, but when I got the scrip filled I didn't take it, called my Dr. and he scolded me - he said I had to take it or I'd get "antibiotic resistance". I took a few more pills but didn't finish the scrip and never went back to that doctor. I began losing weight and my sense of taste. I plateaued until I got COVID in late 2019. They didn't know what it was and sent me home.
I couldn't sleep lying down so I sat in an arm chair and watched my pulse-ox. It wasn't good...
Then after I took my first of 3 600mg NAC for the day I noticed my pulse-ox improved. Some quick googling and I discovered you couldn take a LOT of NAC without doing harm. I started taking 1200 mg doses every 2-3 hours per what my pulse ox readings were. I didn't die.
Unfortunately, COVID also has a mitochondrial effect and my health has been deteriorating since then. My weight went as low as 118 lbs during that period.
I think there are some other folks over at the "Study Hall" that would be interested in this discussion:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=174611386
Xena, Thanks. With Cipro, just curious how long you were on it, and at what approx dose? Did your reaction mainly involve the neuro-psych side, or was it musculo-tendon related, etc, or some combination? Thanks for any info. This is a fascinating topic so I hope you don't mind me asking. It sounds like Dr. Bennett's group has nailed the etiology of the neuro-psych side effects at least. Biological systems and pathways are extremely complex, but with enough digging it should be possible to figure out the main aspects.
---
Hypothyroidism also seems to be a factor, heavily inherited on my mother's side of the family.
https://pubmed.ncbi.nlm.nih.gov/22503787
Xena, I only follow biotech loosely these days, but at one time it was my main sector. One thing to know about the CNS sector is that it has generally been regarded as among the riskiest sectors to invest in within biotech. CNS was where I spent a lot of years (Cortex Pharma - AMPA receptor) but unfortunately with little to show for it. The only riskier area back then was 'gene therapy', which at the time was a brand new.
Your posts on Anavex have me curious, and also the mitochondrial aspect of the Cipro side effects. I'll have to get up to speed. Btw, Dr. Gundry had an entire book (2021) relating to mitochondrial function ('The Energy Paradox') with some interesting revelations on metabolic inflexibility, so it will be interesting to see if there is any potential overlap with your Cipro related condition.
Btw, one thing with Anavex, I can't say that I'm too enthralled with the CEO, based on first impressions anyway. He reminds me somewhat of the former CEO of Cytodyn, who is under investigation by the SEC. Just a vague resemblance though, on the 'vibe' scale. With a small cap bio the character of the CEO is extremely important, and so far with Missling I'm not getting a good vibe, although it's still early.
---
Name | Symbol | % Assets |
---|---|---|
Regeneron Pharmaceuticals Inc | REGN | 2.77% |
Moderna Inc | MRNA | 2.65% |
Gilead Sciences Inc | GILD | 2.43% |
Vertex Pharmaceuticals Inc | VRTX | 2.32% |
Biogen Inc | BIIB | 2.28% |
United Therapeutics Corp | UTHR | 2.26% |
Biomarin Pharmaceutical Inc | BMRN | 2.25% |
Seattle Genetics Inc | SGEN | 2.16% |
Exelixis Inc | EXEL | 2.06% |
ACADIA Pharmaceuticals Inc | ACAD | 2.04% |
Name | Symbol | % Assets |
---|---|---|
Regeneron Pharmaceuticals Inc | REGN | 4.88% |
Gilead Sciences Inc | GILD | 4.58% |
Qiagen NV | QGEN | 4.48% |
Biogen Inc | BIIB | 4.28% |
Seattle Genetics Inc | SGEN | 4.08% |
United Therapeutics Corp | UTHR | 3.93% |
Vertex Pharmaceuticals Inc | VRTX | 3.89% |
ACADIA Pharmaceuticals Inc | ACAD | 3.75% |
Biomarin Pharmaceutical Inc | BMRN | 3.69% |
Alnylam Pharmaceuticals Inc | ALNY | 3.53% |
Name | Symbol | % Assets |
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Pacific Biosciences of California Inc | PACB | 6.85% |
Teladoc Health Inc | TDOC | 5.94% |
CRISPR Therapeutics AG | CRSP | 5.77% |
Twist Bioscience Corp | TWST | 5.72% |
CareDx Inc | CDNA | 3.87% |
Iovance Biotherapeutics Inc | IOVA | 3.59% |
Exact Sciences Corp | EXAS | 3.58% |
Fate Therapeutics Inc | FATE | 3.47% |
Invitae Corp | NVTA | 3.42% |
Personalis Inc | PSNL | 3.26% |
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