Tag: UTIs

Categories : Neurology UrogenitalTags :

New Discovery Reveals the Spinal Cord’s Role in Bladder Control

On By ModernMedia
Urinary incontinence. Credit: Scientific Animations CC4.0

Urinary incontinence is a devastating condition, leading to significant adverse impacts on patients’ mental health and quality of life. Disorders of urination are also a key feature of all neurological disorders.

A USC research team has now made major progress in understanding how the human spinal cord triggers the bladder emptying process. The discovery could lead to exciting new therapies to help patients regain control of this essential function.

In the pioneering study, a team from USC Viterbi School of Engineering and Keck School of Medicine of USC has harnessed functional ultrasound imaging to observe real-time changes in blood flow dynamics in the human spinal cord during bladder filling and emptying.

The work was published in Nature Communications and was led by Charles Liu, the USC Neurorestoration Center director at Keck School of Medicine of USC and professor of biomedical engineering at USC Viterbi, and Vasileios Christopoulos, assistant professor at the Alfred E. Mann Department of Biomedical Engineering.

The spinal cord regulates many essential human functions, including autonomic processes like bladder, bowel, and sexual function. These processes can break down when the spinal cord is damaged or degenerated due to injury, disease, stroke, or aging. However, the spinal cord’s small size and intricate bony enclosure have made it notoriously challenging to study directly in humans.

Unlike in the brain, routine clinical care does not involve invasive electrodes and biopsies in the spinal cord due to the obvious risks of paralysis.

Furthermore, fMRI imaging, which comprises most of human functional neuroimaging, does not exist in practical reality for the spinal cord, especially in the thoracic and lumbar regions where much of the critical function localises.

“The spinal cord is a very undiscovered area,” Christopoulos said. “It’s very surprising to me because when I started doing neuroscience, everybody was talking about the brain. And Dr. Liu and I asked, “What about the spinal cord?”

“For many, it was just a cable that transfers information from the brain to the peripheral system. The truth was that we didn’t know how to go there—how to study the spinal cord in action, visualize its dynamics and truly grasp its role in physiological functions.”

Functional ultrasound imaging: A new window into the spinal cord

To overcome these barriers, the USC team employed functional ultrasound imaging (fUSI), an emerging neuroimaging technology that is minimally invasive. The fUSI process allowed the team to measure where changes in blood volume occur on the spinal cord during the cycle of urination.

However, fUSI requires a “window” through the bone to image the spinal cord. The researchers found a unique opportunity by working with a group of patients undergoing standard-of-care epidural spinal cord stimulation surgery for chronic low back pain.

“During the implantation of the spinal cord stimulator, the window we create in the bone through which we insert the leads gives us a perfect and safe opportunity to image the spinal cord using fUSI with no risk or discomfort to the study volunteers,” said co-first author Darrin Lee, associate director of the USC Neurorestoration Center, who performed the surgeries.

“While the surgical team was preparing the stimulator, we gently filled and emptied the bladder with saline to simulate a full urination cycle under anaesthesia while the research team gathered the fUSI data,” added Evgeniy Kreydin from the Rancho Los Amigos National Rehabilitation Center and the USC Institute of Urology, who was already working closely with Liu to study the brain of stroke patients during micturition using fMRI.

“This is the first study where we’ve shown that there are areas in the spinal cord where activity is correlated with the pressure inside the bladder,” Christopoulos said.

“Nobody had ever shown a network in the spinal cord correlated with bladder pressure. What this means is I can look at the activity of your spinal cord in these specific areas and tell you your stage of the bladder cycle – how full your bladder is and whether you’re about to urinate.”

Christopoulos said the experiments identified that some spinal cord regions showed positive correlation, meaning their activity increased as bladder pressure rose, while others showed negative (anti-correlation), with activity decreasing as pressure increased. This suggests the involvement of both excitatory and inhibitory spinal cord networks in bladder control.

“It was extremely exciting to take data straight from the fUSI scanner in the OR to the lab, where advanced data science techniques quickly revealed results that have never been seen before, even in animal models, let alone in humans,” said co-first author Kofi Agyeman, biomedical engineering postdoc.

New hope for patients

Liu has worked for two decades at the intersection of engineering and medicine to develop transformative strategies to restore function to the nervous system. Christopoulos has spent much of his research career developing neuromodulation techniques to help patients regain motor control.

Together, they noted that for patients, retaining control of the autonomic processes that many of us take for granted is more fundamental than even walking.

“If you ask these patients, the most important function they wanted to restore was not their motor or sensory function. It was things like sexual function and bowel and bladder control,” Christopoulos said, noting that urinary dysfunction often leads to poor mental health. “It’s a very dehumanising problem to deal with.”

Worse still, urinary incontinence leads to more frequent urinary tract infections (UTIs) because patients must often be fitted with a catheter. Due to limited sensory function, they may not be able to feel that they have an infection until it is more severe and has spread to the kidneys, resulting in hospitalisation.

This study offers a tangible path toward addressing this critical need for patients suffering from neurogenic lower urinary tract dysfunction. The ability to decode bladder pressure from spinal cord activity provides proof-of-concept for developing personalised spinal cord interfaces that could warn patients about their bladder state, helping them regain control.

Currently, almost all neuromodulation strategies for disorders of micturition are focused on the lower urinary tract, largely because the neural basis of this critical process remains unclear.

“One has to understand a process before one can rationally improve it,” Liu said.

This latest research marks a significant step forward, opening new avenues for precision medicine interventions that combine invasive and noninvasive neuromodulation with pharmacological therapeutics to make neurorestoration of the genitourinary system a clinical reality for millions worldwide.

Source: University of Southern Carolina

Categories : AntibioticsTags :

Bacterial Stress Drives the Development of Antibiotic Resistance

On By ModernMedia
Photo by CDC on Unsplash

Antibiotics are supposed to wipe out bacteria, yet the drugs can sometimes hand microbes an unexpected advantage.

A new Nature Communications study from Rutgers Health shows that ciprofloxacin, a staple treatment for urinary tract infections, throws Escherichia coli into an energy crisis that saves many cells from death and speeds the evolution of full‑blown resistance.

“Antibiotics can actually change bacterial metabolism,” said first author Barry Li, a student at Rutgers pursuing a dual doctoral degree for physician–scientists. “We wanted to see what those changes do to the bugs’ chances of survival.”

Li and senior author Jason Yang focused on adenosine triphosphate (ATP), the molecular fuel of cells. When ATP levels crash, cells experience “bioenergetic stress.” To mimic that stress, the team engineered E. coli with genetic drains that constantly burned ATP or its cousin nicotinamide adenine dinucleotide (NADH). Then, they pitted both the engineered strains and normal bacteria against ciprofloxacin.

The results surprised the researchers. The drug and the genetic drains each slashed ATP, but rather than slowing down, the bacteria revved up. Respiration soared, and the cells spewed extra reactive‑oxygen molecules that can damage DNA. That frenzy produced two troubling outcomes.

First, more of the bacteria cells survived.

In time‑kill tests, ten times as many stressed cells survived a lethal ciprofloxacin dose compared with unstressed controls. These hardy stragglers, called persister cells, lie low until the drug is gone and then rebound to launch a new infection.

People have long blamed sluggish metabolism for persister cell formation.

“People expected a slower metabolism to cause less killing,” Li said. “We saw the opposite. The cells ramp up metabolism to refill their energy tanks, and that turns on stress responses that slow the killing.”

Follow‑up experiments traced the protection to the stringent response, a bacterial alarm system that reprograms the cell under stress.

Second, stressed cells mutated faster to evolve antibiotic resistance.

While persisters keep infections smoldering, genetic resistance can render a drug useless outright. The Rutgers group cycled E. coli through escalating ciprofloxacin doses and found that stressed cells reached the resistance threshold four rounds sooner than normal cells. DNA sequencing and classic mutation tests pointed to oxidative damage and error‑prone repair as the culprits.

“The changes in metabolism are making antibiotics work less well and helping bacteria evolve resistance,” said Yang, an assistant professor at the medical school and Chancellor Scholar of microbiology, biochemistry & molecular genetics.

Preliminary measurements show that gentamicin and ampicillin also drain ATP in addition to ciprofloxacin. The stress effect may span very different pathogens, including the pathogen Mycobacterium tuberculosis, which is highly sensitive to ATP shocks.

If so, the discovery casts new light on a global threat. Antibiotic resistance already contributes to 1.27 million deaths a year. Strategies that ignore the metabolic fallout of treatment may be missing a key lever.

The findings suggest several changes for antibiotic development and use.

First, screen candidate antibiotics for unintended energy‑drain side effects. Second, pair existing drugs with anti‑evolution boosters that block the stress pathways or mop up the extra oxygen radicals. Third, reconsider the instinct to blast infections with the highest possible dose. Earlier studies and the new data both hint that extreme concentrations can trigger the very stress that protects bacteria.

“Bacteria turn our attack into a training camp,” Yang said. “If we can cut the power to that camp, we can keep our antibiotics working longer.”

Li and Yang are planning on testing compounds that soothe bioenergetic stress in the hope of turning the microbial energy crisis back into an Achilles’ heel rather than a shield.

Source: Rutgers University

Categories : Ethics and Law UrogenitalTags :

Court Rules that UTI Drug Trade Names are Too Similar

On By ModernMedia
Photo by Bill Oxford on Unsplash

A court case over the trade names of two urinary tract infection (UTI) drugs has been settled. The court ordered that Cipla Medpro be restrained from using the trade name Furizome as it is too similar to Adcock Ingram’s UTI drug Urizone, leading to potential confusion by consumers. In his ruling, Justice James Lekhuleni of the High Court, Western Cape Division, who stated that despite safeguards against confusion in prescribing, ultimately “doctors are human”, so miscommunications could occur – and that the agency of patients cannot be ignored.

The trademark infringement case was brought by three applicants: Adcock Ingram Limited, Adcock Ingram Healthcare (Pty) LTD, and Italian company Zambon S.P.A. Zambon is the owner of the name Urizone, which is used under licence. Urizone had been launched in South Africa in 1993. The applicants stated that more than 3 million sachets had been sold between 2011 and 2023, with R5 million in advertising spent to promote the drug between 2018 and 2022 alone.

The applicants brought the case that Cipla Medpro’s Furizome, with the active ingredient fosfomycin, was too similar to their own product, Urizone, which contained the same ingredient in 3g sachets, and thus could confuse consumers. They alleged that Cipla Medpro sought to capitalise on the reputation earned by Urizone.

The applicants made the case that, despite Urizone being made available as a generic, none of the pharmaceutical companies producing it chose to use the name. When Furizome was launched, Adcock Ingram sent a letter of demand to Cipla to stop using the name due to its . Cipla, through its attorneys, rebutted the claim, saying that the two are sufficiently distinct to avoid confusion, with the “F” alluding to the fosfomycin ingredient. Cipla contended that it had already submitted the name through SAHPRA, and

Cipla also contended that the consumer – the patient – would not be misled during the prescribing and purchase of a schedule 4 medication as they would be informed by the pharmacist of the two different drugs.

In considering the judgment, the court noted that a test as to whether trademarks are be similar can be mode on a phonetic basis, or if they conceptually or visually similar. A trademark’s essential function is to indicate the origin of the goods in connection with which it is used. The “N” and “M” where seen as visually and phonetically similar, and “furi” was similar phonetically to “uri“. This could cause confusion and miscommunication even between doctors as to what drug they had prescribed a patient.

While Justice Lekhuleni acknowledged the safeguards of prescribing schedule 4 medications, he pointed out that the general public had become much more knowledgeable about prescription drugs in the past two decades. On this, he wrote “…the reality is that patients are involved in the process of deciding which medicines they will use, and that creates the risk of confusion. This situation in turn creates a responsibility upon pharmaceutical companies to make sure that they adopt trade marks that are not confusingly similar.”

Categories : UrogenitalTags :

UTI Pain Stems from Hypersensitivity in Nerves for Bladder Fullness

On By ModernMedia
Photo by Jan Antonin Kolar on Unsplash

New insights into what causes the painful and disruptive symptoms of urinary tract infections (UTIs) could offer hope for improved treatment. Nearly one in three women will experience UTIs before the age of 24, and many elderly people and those with bladder issues from spinal cord injuries can experience multiple UTI’s in a single year.

Findings from a new study led by Flinders University’s Dr Luke Grundy and SAHMRI’s Dr Steven Taylor show that UTIs cause the nerves in the bladder to become hypersensitive resulting in the extremely painful and frequent urge to urinate, pelvic pain, and burning pain while urinating.

“We found that UTIs, caused by bacterial infections such as E. coli, can significantly alter the function and sensitivity of the nerves that usually detect bladder fulness, a phenomenon known as ‘bladder afferent hypersensitivity’, says Dr Grundy, from the College of Medicine and Public Health.

“The study was the first of its kind to explore the impact of UTIs on the sensory signals that travel from the bladder to the brain, and the direct link this response has to causing bladder pain and dysfunction.”

A normal bladder will expand to store urine and can store up to two cups of urine for several hours.  Once full, the bladders nervous system will signal that it is time to urinate, or empty the bladder.

Described in Brain, Behavior, & Immunity – Health, researchers analysed how UTIs cause sensory nerves that respond to bladder distension to become hypersensitive, so that they send signals of bladder fulness, even when the bladder is not yet full.

“Our findings show that UTIs cause the nerves in the bladder to become overly sensitive, which means that even when the bladder is only partly filled, it can trigger painful bladder sensations that would signal for the need to urinate,” he says.

“We think that these heightened sensory responses may serve as a protective mechanism, alerting the body to the infection and prompting more frequent urination to expel the bacteria.”

Building on previous research, the new study reveals a deeper understanding of how UTIs affect bladder function and the nervous system, and raises important questions about the role of bladder hypersensitivity in the development of UTI-related symptoms.

“Our findings go further in identifying the significant changes that occur during UTIs and provide a clearer picture of the mechanisms behind the painful and disruptive bladder sensations often associated with these infections,” says Dr Grundy.

The study also suggests that better understanding and targeting of bladder afferent hypersensitivity could improve treatment options for patients suffering from recurrent UTIs or other bladder conditions where sensory dysfunction plays a role.

“Theoretically we should be able to find a way to address hypersensitive nerves in the bladder and reduce or eliminate the painful and debilitating symptoms of a UTI,” he adds. This would improve quality of life whilst antibiotics are taking care of the infection.

Researchers are striving to address the limited treatments available for bladder pain by exploring how the findings may translate into clinical practice and improve the management of UTIs in patients.

Source: Flinders University

Categories : Neurology UrogenitalTags :

Scientists Identify a Type of Brain Cell That is a Master Controller of Urination

On By ModernMedia
Photo by Jan Antonin Kolar on Unsplash

Researchers have identified a subset of brain cells in mice that act as the master regulators of urination.

The research, published as a Reviewed Preprint in eLife, is described by editors as an important study with convincing data showing that oestrogen receptor 1-expressing neurons (ESR1+) in the Barrington’s nucleus of the mouse brain coordinate both bladder contraction and relaxation of the external urethral sphincter.

Urination requires the coordinated function of two units of the lower urinary tract. The detrusor muscle of the bladder wall relaxes to allow the bladder to fill and empty, while the external sphincter opens when it’s appropriate to allow urine to flow out, but otherwise keeps tightly shut.

“Impairment of coordination between the bladder muscle and the sphincter leads to various urinary tract dysfunctions and can significantly degrade a person’s quality of life,” says first author Xing Li, Advanced Institute for Brain and Intelligence, School of Physical Science and Technology, Guangxi University, Nanning, China. “But although we know the individual nerve signalling pathways that control each of these urinary tract components, we don’t know which brain areas ensure they cooperate at the right time.”

To explore this, the authors used state-of-the-art live cell imaging to study the activity of brain cells in anaesthetised and awake mice during urination. They focused on a brain region called the pontine micturition centre (PMC), otherwise known as the Barrington’s nucleus, and compared the activity of different PMC nerve cell subtypes.

In their first experiments, they measured the activity of the cells as the bladder empties by measuring changes in levels of calcium. This revealed that the electrical firing rate of a subset of PMC cells expressing estrogen receptors (PMCESR1+ cells) was tightly linked to bladder emptying. When they combined this with monitoring bladder physiology, they found that it was not only the timing of PMCESR1+ cell activity that correlated with bladder emptying, but the strength of cell electrical activity, too.

Next, they tested what happened to urination if they blocked or triggered the PMCESR1+ cells. They found that when PMCESR1+ cell activity was blocked, the amount of urine the mice passed was significantly reduced and ongoing urination was suspended from the moment the cells were inactive. To understand the mechanism behind this, they measured the activity of the bladder muscle and sphincter. They discovered that both increase of bladder pressure and sphincter muscle bursting activity associated with bladder emptying both stopped when PMCESR1+ cell activity was blocked during an ongoing voiding even. Similarly, when PMCESR1+ cells were artificially activated using light, bladder emptying occurred 100% of the time. This suggests that PMCESR1+ cells work as a reliable master switch that either initiates or suspends bladder emptying.

To test whether PMCESR1+ cells can influence bladder emptying independently of controlling the sphincter, they disconnected either the nerve carrying messages from the brain to the sphincter, or the nerve carrying messages from the brain to the bladder. They found that PMCESR1+ cell control of the bladder was fully operational even when communication to the sphincter was blocked, and vice versa. This showed the cells could control the bladder and sphincter independently of one another, but the question remained: could they coordinate the action of the bladder muscle and sphincter together? That is, operate them in a controlled, perfectly timed manner, to trigger bladder emptying when appropriate?

To explore this, they simultaneously recorded bladder pressure and electromyography measurements of sphincter activity. The timing of bladder pressure changes immediately before sphincter bursting activity was consistent for both spontaneous bladder emptying and emptying caused by activating the PMCESR1+ cells, showing that these cells can coordinate the two steps in a precisely temporal sequence and controlled way.

“Our study shows that a subset of cells in the Barrington’s nucleus of the brain can initiate and suspend bladder emptying with 100% accuracy when needed, for example, to release only a small volume for landmarking by animals, or for a human to urinate into a small sample tube for a health check,” concludes senior author Xiaowei Chen, Third Military Medical University, and Chongqing Institute for Brain and Intelligence, China. “While other cells will no doubt be involved in perfect urination control, our pinpointing of PMCESR1+ cells’ crucial role in bladder–sphincter coordination will aid the development of targeted therapies for treating urination dysfunction caused by brain or spinal cord injury or peripheral nerve damage.”

Source: eLife

Categories : Diet and NutritionTags :

Drinking Plenty of Water may Actually be Good for You

On By ModernMedia
Photo by Amanda María on Unsplash

Public health recommendations generally suggest drinking eight cups of water a day. And many people just assume it’s healthy to drink plenty of water.

Now researchers at UC San Francisco have taken a systematic look at the available evidence, analysed 18 randomised controlled trials. In their review, published in JAMA Network Open, they concluded that drinking enough water can help with weight loss and prevent kidney stones, as well as migraines, urinary tract infections and low blood pressure.

“For such a ubiquitous and simple intervention, the evidence hasn’t been clear, and the benefits were not well established, so we wanted to take a closer look,” said Benjamin Breyer, MD, MAS, professor and chair of the UCSF Department of Urology.

“The amount of rigorous research turned out to be limited, but in some specific areas, there was a statistically significant benefit,” said Breyer, the senior author of the study. “To our knowledge, this is the first study assessing the benefits of water consumption on clinical outcomes broadly.”

Strong evidence suggested that drinking eight cups of water a day significantly decreased the likelihood of getting another kidney stone. Several studies found that drinking about six cups of water a day helped adults lose weight. But a study that included adolescents found that drinking a little more than eight cups of water a day had no effect.

Still, the authors said that encouraging people to drink water before meals would be a simple and cheap intervention that could have huge benefits, given the increased prevalence of obesity.

Other studies indicated that water can help prevent migraines, control diabetes and low blood pressure, and prevent urinary tract infections. Adults with recurrent headaches felt better after three months of drinking more water. Drinking about four more cups of water a day helped diabetic patients whose blood glucose levels were elevated.

Drinking an additional six cups a day of water also helped women with recurrent urinary tract infections. It reduced the number of infections and increased the amount of time between them. Drinking more water also helped young adults with low blood pressure.

“We know that dehydration is detrimental, particularly in someone with a history of kidney stones or urinary infections,” Breyer said. “On the other hand, someone who suffers from frequent urination at times may benefit from drinking less. There isn’t a one size fits all approach for water consumption.”

Source: University of California – San Francisco

Categories : Diseases, Syndromes and Conditions UrogenitalTags :

Cranberry Products for UTI Prevention Really Do Work

On By ModernMedia

A global study looking at the benefits of cranberry products has determined that cranberry juice, and its supplements, reduce the risk of repeat symptomatic UTIs in women by more than a quarter. The study researchers, from Flinders University and The Children’s Hospital at Westmead, also found that was reduced in children by more than half, and in people susceptible to UTI following medical interventions by about 53%.

Cranberry juice and healthcare supplements that commonly include the fruit, such as capsules and tablets, have long been promoted as a readily available solution to ward off the infection but the most recent review in 2012, with evidence from 24 trials, showed no benefit from the products.

The medical scientists behind this updated review published in Cochrane Reviews aimed to update these findings, as by looking at 50 more recent trials that included almost 9000 participants.

“This incredible result didn’t really surprise us, as we’re taught that when there’s more and better evidence, the truth will ultimately come out. UTIs are horrible and very common; about a third of women will experience one, as will many elderly people and also people with bladder issues from spinal cord injury or other conditions,” says the study lead author Dr Gabrielle Williams.

“Even back in 1973, my mum was told to try cranberry juice to prevent her horrible and frequent UTIs, and for her it’s been a saviour. Despite me niggling in her ear about evidence, she’s continued to take it daily, first as the nasty sour juice and in recent years, the easy to swallow capsules. As soon as she stops, wham the symptoms are back. As usual, it turns out that mum was right! Cranberry products can help some women prevent UTIs.”

Flinders University epidemiologist Dr Jacqueline Stephens, a co-author of the study, says if the UTI persists untreated it can move to the kidneys and cause pain and more complications, including sepsis in very severe cases, so prevention is the most effective way to reduce risks.

“Most UTIs are effectively, and pretty quickly, treated with antibiotics, sometimes as little as one dose can cure the problem. Unfortunately, in some people UTIs keep coming back. Without being sure if or how it works, some healthcare providers began suggesting it to their patients. It was a harmless, easy option at the time. Even centuries ago, Native Americans reportedly ate cranberries for bladder problems, leading somewhat more recently, to laboratory scientists exploring what it was in cranberries that helped and how it might work.”

“The studies we looked at included a range of methods to determine the benefits of cranberry products. The vast majority compared cranberry products with a placebo or no treatment for UTI and determined drinking cranberries as a juice or taking capsules reduced the number of UTIs in women with recurrent cases, in children and in people susceptible to UTi’s following medical interventions such as bladder radiotherapy.”

“It’s also important to consider that few people reported any side effects with the most common being tummy pain based on the results. We also did not find enough information to determine if cranberry products are more or less effective compared with antibiotics or probiotics in preventing further UTIs.”

The data also doesn’t show any benefit for elderly people, pregnant women or in people with bladder emptying problems.

The study’s senior author, Professor Jonathan Craig, says the real benefits of cranberry products became clear when the researchers expanded the scope of the review to include the most recently available clinical data.

“This is a review of the totality of the evidence and as new evidence emerges, new findings might occur. In this case, the new evidence shows a very positive finding that cranberry juice can prevent UTI in susceptible people,” says Professor Craig.

“We have shown the efficacy of cranberry products for the treatment of UTIs using all the evidence published on this topic since the mid-nineties. The earlier versions of this review didn’t have enough evidence to determine efficacy and subsequent clinical trials showed varied results, but in this updated review the volume of data has shown this new finding.”

The study authors conclude that while cranberry products do help prevent UTIs in women with frequent recurrence, more studies are needed to further clarify who with UTI would benefit most from cranberry products.

Source: Flinders University

Categories : Obstetrics & Gynaecology UrogenitalTags :

Oestrogen may Protect against Delirium in Older Women with UTIs

On By ModernMedia
Photo by Karolina Grabowska

Delirium is common among women with urinary tract infections (UTIs) – especially those who have experienced menopause. In mouse models, researchers have been able to prevent symptoms of the condition by administering oestrogen. Their study was published in the peer-reviewed journal Scientific Reports.

“There has been a resurgence of interest in hormone replacement therapy, and this study, which builds on our previous work, shows that it may be a tool to mitigate delirium,” said Shouri Lahiri, MD, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai and senior author of the study. “I think it is a major step toward a clinical trial of oestrogen in human patients with UTIs.”

Lahiri said that delirium is a common problem in older women with UTIs.

“Even as a medical student, you know that if an older woman comes to the hospital and she’s confused, one of the first things you check is whether the patient has a UTI,” Lahiri said.

In previous studies, Lahiri’s team found a connection between delirium and an immune-regulating protein called interleukin 6 (IL-6). Events such as lung injury or UTI cause IL-6 to travel through the blood to the brain, causing symptoms such as disorientation and confusion. Oestrogen is a known suppressor of IL-6, so the investigators designed experiments to test its effects on UTI-induced delirium.

The researchers compared pre- and postmenopausal mice with UTIs and observed their behaviour in several types of specialised environments. They found that the mice in which menopause had been induced exhibited symptoms of delirium, such as anxiousness and confusion, while the others did not.

When they treated the mice with oestrogen, levels of IL-6 in the blood and delirium-like behaviour were greatly reduced. The behavioural differences were not related to UTI severity, as bacterial levels in the urine weren’t markedly different between the two groups, Lahiri said.

The investigators also looked at the direct effects of oestrogen on neurons, using what Lahiri called a “UTI in a dish.”

“We exposed individual neurons to an IL-6 inflammation cocktail to create UTI-like injury,” Lahiri said. “But when we added oestrogen to the cocktail, it mitigated the injury. So, we showed that there are at least two ways that oestrogen helps reduce symptoms of delirium. It reduces IL-6 levels in the blood and protects the neurons directly.”

Just how oestrogen acts to protect neurons is still unexplained. And before conducting a clinical trial, researchers need to identify which patients with UTIs are most likely to experience delirium and at what point oestrogen treatment might be most effective.

“Currently, it is common practice to treat UTI-induced delirium using antibiotics, even though there are no clinical trials that indicate this practice is effective and it is not supported by clinical practice guidelines,” said Nancy Sicotte, MD, chair of the Department of Neurology and the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai. “This work is an important step in determining whether modulating immune response via oestrogen replacement or other means is a more effective treatment.”

The team is also working to understand the different effects of delirium on females versus males, which was not a topic of this study. Effective treatment of delirium could be of long-term importance, Lahiri said, because it is a known risk factor for long-term cognitive impairments, such as Alzheimer’s disease and related dementia.

Source: Cedars-Sinai Medical Center

Categories : UrogenitalTags :

New Drug Combination More Effective in Treating Urinary Tract Infections

On By ModernMedia
E. Coli bacteria. Image by CDC
E. Coli bacteria. Image by CDC

An international study published in JAMA comparing new and older treatments against complicated urinary tract infections has found that a new drug combination of cefepime and enmetazobactam to be more effective, especially against drug-resistant strains.

Researchers in the ALLIUM Phase 3 clinical trial showed that a combination of the drugs cefepime and enmetazobactam was more effective in treating both complicated urinary tract infections (UTIs) and acute pyelonephritis (AP), a bacterial infection causing kidney inflammation, than the standard combination of piperacillin and tazobactam. UTIs are considered complicated when they are associated with risk factors such as fevers, sepsis, urinary obstruction or catheters, that increase the danger of failing antibiotic therapy.

“This new antibiotic was superior to the standard-of-care therapy,” said Professor Keith Kaye at Rutgers Robert Wood Johnson Medical School, the study’s lead author. “It represents an exciting option for treatment.”

Prof Kaye added this drug combination also fights an often-dangerous category of bacterial illnesses caused by pathogens known as extended spectrum beta-lactamase (ESBL) infections, named for an enzyme the bacteria produce. ESBL-producing bacteria can’t be killed effectively by many of the antibiotics conventionally used to treat infections, such as penicillins and cephalosporins.

“We are looking for antibiotics that are active against resistant bacteria, such as ESBLs, and we found this new combination to be highly effective,” Prof Kaye said.

The trial was conducted at 90 sites in Europe, North and Central America, South America and South Africa from September 2018 to November 2019. More than 1000 patients participated in the study. Some 79% of the patients receiving the new combination of cefepime and enmetazobactam were successfully treated for their illness, as opposed to 58.9% of those receiving the conventional treatment of piperacillin and tazobactam.

Of the 20% of patients from the overall group belonging to the subset of those with ESBL infections, 73% receiving cefepime and enmetazobactam achieved a clinical cure, as opposed to 51% on the standard therapy.

The antibiotic cefepime is a fourth-generation cephalosporin that was approved for use in the 1990s and is available generically. Enmetazobactam, an experimental drug made by the French biopharmaceutical company Allecra Therapeutics, is a beta-lactamase inhibitor, meaning it attacks the beta-lactamases, including the types of enzymes produced by ESBL-producing bacteria. The drug combination has been fast-tracked for approval by the U.S. Food and Drug Administration (FDA).

Source: Rutger University

Categories : Diseases, Syndromes and Conditions Metabolic DisordersTags :

New Study Explains Diabetes and UTI Link

On By ModernMedia
Huge clumps of E. coli (red) infecting diabetic mouse bladder. Photo: Soumitra Mohanty

Lower immunity and recurring infections are common in type 1 and type 2 diabetes. Research has shown that the immune system of people with diabetes has lower levels of the antimicrobial peptide psoriasin, which compromises the urinary bladder’s cell barrier, increasing the risk of urinary tract infection. The study is published in Nature Communications.

One effect of diabetes is that it compromises the innate immune system, leaving many people with increased susceptibility to regular infections, such as urinary tract infections (UTI)s caused by E. coli bacteria. In people with diabetes, these are more likely to lead to general blood poisoning, sepsis, originating in the urinary tract.

An endogenous antibiotic

Karolinska Institutet researchers investigated whether glucose levels in people with diabetes (type 1, type 2, or prediabetes) are linked with psoriasin, an endogenous antibiotic which is a part of the innate immune system.

Using samples of urine, bladder cells and blood serum from patients, the researchers analysed levels of psoriasin and other peptides necessary for ensuring that the bladder mucosa remains intact and protects against infection. The findings were then verified in mice and urinary bladder cells with and without infection.

“We found that high glucose concentrations reduce the levels of the antimicrobial peptide psoriasin, while insulin has no effect,” said Professor Annelie Brauner, who led the study. “People with diabetes have lower levels of psoriasin, which weakens the cells’ protective barrier function and increases the risk of bladder infection.”

Oestrogen therapy reduced bacterial population

Professor Brauner’s research group has previously shown that oestrogen restores the protective function of bladder cells in humans and mice and thereby help to regulate the immune response to a UTI. The researchers therefore tested how oestrogen treatment affects infected cells exposed to high glucose concentrations. They found that the treatment boosted levels of psoriasin and reduced bacterial populations, indicating that the treatment may have an effect also among patients with diabetes.

“We now plan to probe deeper into the underlying mechanisms of infections in individuals with diabetes,” said lead author Soumitra Mohanty. “The ultimate goal is to reduce the risk of infection in this growing patient group.”

Source: Karolinska Institutet