Day: May 29, 2023

Categories : Metabolic Disorders New Compounds and TreatmentsTags : Leave a comment

Experimental Drug may Prevent Diabetic Vision Loss

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Researchers at Wilmer Eye Institute, Johns Hopkins Medicine say they have evidence that an experimental drug may prevent or slow vision loss in people with diabetes. The results are from a study published in the Journal of Clinical Investigation, that used mouse models as well as human retinal organoids and eye cell lines.

The team focused on models of two common diabetic eye conditions: proliferative diabetic retinopathy and diabetic macular enema, both of which affect the retina, the light-sensing tissue at the back of the eye that also transmits vision signals to the brain. In proliferative diabetic retinopathy, new blood vessels overgrow on the retina’s surface, causing bleeding or retinal detachments and profound vision loss. In diabetic macular enema, blood vessels in the eye leak fluid, leading to swelling of the central retina, damaging the retinal cells responsible for central vision.

Results of the study show that a compound called 32-134D, previously shown to slow liver tumour growth in mice, prevented diabetic retinal vascular disease by decreasing levels of a protein called HIF, or hypoxia-inducible factor. Doses of 32-134D also appeared to be safer than another treatment that also targets HIF and is under investigation to treat diabetic eye disease.

Current treatment for both proliferative diabetic retinopathy and diabetic macular enema includes eye injections with anti-vascular endothelial growth factor (anti-VEGF) therapies. Anti-VEGF therapies can halt the growth and leakiness of blood vessels in the retina in patients with diabetes. However, these treatments aren’t effective for many patients, and may cause side effects with prolonged use, such as increased internal eye pressure or eye tissue damage.

Study author Akrit Sodhi, MD, PhD, says that in general, the idea of inhibiting HIF, a fundamental protein in the body, has raised concerns about toxicity to many tissues and organs. But when his team screened a library of HIF inhibitor drugs and conducted extensive testing, “We came to find that the drug examined in this study, 32-134D, was remarkably well tolerated in the eyes and effectively reduced HIF levels in diseased eyes,” says Sodhi.

HIF, a type of protein known as a transcription factor, has the ability to switch certain genes, including vascular endothelial growth factor (VEGF), on or off throughout the body. In the eye, elevated levels of HIF cause genes like VEGF to increase blood vessel production and leakiness in the retina, contributing to vision loss.

To test 32-134D, researchers dosed multiple types of human retinal cell lines associated with the expression of proteins that promote blood vessel production and leakiness. When they measured genes regulated by HIF in cells treated with 32-134D, they found that their expression had returned to near-normal levels, which is enough to halt new blood vessel creation and maintain blood vessels’ structural integrity.

Researchers also tested 32-134D in two different adult mouse models of diabetic eye disease. In both models, injections were administered into the eye. Five days post-injection, the researchers observed diminished levels of HIF, and also saw that the drug effectively inhibited the creation of new blood vessels or blocked vessel leakage, therefore slowing progression of the animals’ eye disease. Sodhi and his team said they also were surprised to find that 32-134D lasted in the retina at active levels for about 12 days following a single injection without causing retinal cell death or tissue wasting.

“This paper highlights how inhibiting HIF with 32-134D is not just a potentially effective therapeutic approach, but a safe one, too,” says Sodhi. “People facing diabetic eye disease and vision loss include our family members, friends, co-workers – this is a disease that impacts a large group of people. Having safer therapies is critical for this growing population of patients.”

Sodhi says that further studies in animal models are needed before moving to clinical trials.

Source: Johns Hopkins Medicine

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Nonalcoholic Fatty Liver Disease Comes with an Increased Infection Risk

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A Swedish study of more than 12 000 patients with nonalcoholic fatty liver disease (NAFLD) revealed a significantly increased risk of severe infections requiring hospital admission. The study was published in Clinical Gastroenterology and Hepatology.

NAFLD is considered a manifestation of the metabolic syndrome in the liver and with the global rise in obesity, NAFLD has emerged as the most common chronic liver disease affecting around one quarter of all adults worldwide. Being such a wide-spread disease, it has also become the fastest growing cause of end-stage liver disease, primary liver cancer and liver transplantation. In recent years, NAFLD is increasingly viewed as a multifaceted disease affecting multiple organ systems.

In the ESPRESSO study, involving 12 133 individuals with biopsy-proven NAFLD, and 57 516 matched controls from the general population, NAFLD was associated with a 71% higher risk for severe infections requiring hospital admission. The researchers found that individuals with NAFLD exhibited the same spectrum of infection sites as compared with the general population – with respiratory and urogenital tract infections being the two most common sites of infection.

“Our work is important as the first nationwide study assessing the risk of infections in individuals diagnosed with NAFLD”, says lead author Dr Fahim Ebrahimi, MD, MSc, postdoctoral researcher at Karolinska Institutet and gastroenterologist at Clarunis University Center for Gastrointestinal and Liver Diseases in Basel, Switzerland. “Our findings highlight the importance of NAFLD as a multisystem disorder that increases the risk of infections independent from other underlying risk factors such as diabetes mellitus.”

Risk differences for infections

The researchers were intrigued by previous experimental studies that suggested that NAFLD is associated with impaired function of several immune cells which may lead to higher susceptibility towards various viral, bacterial, and fungal infections. “The liver plays a significant role in the human immune system with immune cells, such as macrophages (Kupffer cells) and lymphocytes, constituting up to 20% of all liver cells”, adds Dr. Ebrahimi. “We were surprised to find that the risk of severe infections was increased even in people with simple fatty liver disease without evidence of any liver inflammation or fibrosis. However, when individuals had evidence of the inflammatory subtype nonalcoholic steatohepatitis (NASH), or had developed fibrosis, they were at even higher risks with the highest risks among those with cirrhosis.”

“The absolute risk difference at 20 years after NAFLD diagnosis was 17.3%, equal to one extra severe infection in every 6 patients with NAFLD, therefore, our findings underline the importance of early diagnosis and treatment to reverse the disease at all stages”, says corresponding author Jonas F Ludvigsson, paediatrician at Örebro University Hospital, and professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.

“To date, clinical guidelines on NAFLD have not yet included specific recommendations for preventing and managing infections”, says Dr Ebrahimi. “Based on our results, prevention of infections should become one of the main public health efforts to tackle NAFLD associated morbidities.”

Source: Karolinksa Insitutet

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500-year-old Horn Container Discovered in South Africa Sheds Light on Pre-colonial Khoisan Medicines

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Both the Khoi and the San believed in a mythical animal, resembling a cow, whose horns were thought to have medicinal attributes. Credit: Rodger Smith

By Justin Bradfield, The Conversation

In 2020, a chance discovery near the small South African hamlet of Misgund in the Eastern Cape unearthed an unusual parcel – a gift to science. The parcel turned out to be a 500-year-old cow horn, capped with a leather lid and carefully wrapped in grass and the leafy scales of a Bushman poison bulb (Boophane disticha). Inside the horn were the solidified remnants of a once-liquid substance.

Thanks to chemical analyses, we now know that the horn was a medicine container. It is the earliest known object of its kind from anywhere in southern Africa and offers the first insights into pre-colonial medicines in this part of the world.

My colleagues and I conducted chemical analyses of the contents. We identified several secondary plant metabolites, the most abundant of which were mono-methyl inositol and lupeol. Both of these compounds, and indeed all of those identified, have known medicinal properties.

This remarkable find is the oldest example in southern Africa, of which we are aware, of two or more plant ingredients being purposefully combined into a container to form a medicinal recipe. Several museums in South Africa house examples of medicine horns collected during the 19th and 20th centuries – but none has ever been found in an archaeological context.

Various plant uses

The medicine container was found in a painted rock shelter. A radio carbon date of the horn container places the parcel at around AD 1461-1630. Although the rock shelter contains several San paintings, we do not know if they are the same age as the horn container. At this time the area was occupied by both San hunter-gatherers and Khoi pastoralists; both believed in a mythical animal, resembling a domestic cow, whose horns were considered to have medicinal attributes.

People have exploited the pharmacological properties of plants for at least the last 200 000 years. The descendants of these communities still live in Southern Africa today. During the Middle Stone Age (which started about 300 000 years ago and ended between 50 000 and 20 000 years ago), people burnt certain aromatic leaves to fumigate their sleeping areas. Plant extracts also seem to have been the main component of glues and adhesives and hunting poisons around this time.

But not much is known about traditional medicines from the pre-colonial era of southern Africa. What information there is derives mainly from early traveller accounts and modern ethnographic studies. The horn offered us a chance to learn a little more about traditional knowledge of medicine and pharmacology during this early period.

The descendants of these communities still live in southern Africa today.

Medical and spiritual applications

The main compounds present in the container, mono-methyl inositol and lupeol, are still found today in a variety of known medicinal plants in the Eastern Cape. They have a wide range of recorded medicinal applications, including the control of blood sugar and cholesterol levels, and treatment of fevers, inflammation and urinary tract infections. They can also be applied topically to treat infections – rubbing ointment into cuts in the skin is one of the ways the San are known to have administered certain medicines.

Both mono-methyl inositol and lupeol are pharmacologically safe compounds. This means that they can be ingested without the risk of overdose. Both compounds stimulate the production of dopamine in the brain; mono-methyl inositol is used to treat anxiety, and plants containing lupeol are used as aphrodisiacs.

For the Khoi and San people, not all medicines were meant to treat physiological illnesses. Healers were specialised individuals whose task was to treat both physical and spiritual ailments. Indeed, one of the principal functions of traditional medicine, both in the past and today, is to treat supernatural bewitchment. Medicine and culture remain intimately entwined and traditional medicine, which is highly adaptive, continues to play an important role in much of Africa as a primary health service.

A treasured possession

We cannot know exactly what the medicine stored in the horn was used for, how it was administered or who precisely used it. But it was clearly a treasured possession, judging by the way it was carefully wrapped and deposited in the rock shelter. Its owner evidently intended to retrieve it but never returned.

The absence of any evidence of long-term occupation of the shelter means that the medicine horn is an isolated, chance discovery. Nevertheless, this is a find that sheds new light on traditional medicines used in the Eastern Cape 500 years ago.

This article is republished from The Conversation under a Creative Commons license.

Source: The Conversation

Categories : Cardiovascular DiseaseTags : Leave a comment

New Care Bundle Boosts Intracerebral Haemorrhage Survival and Outcomes

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Photo by Alex Fedini on Pixabay

New data from the phase III INTERACT3 study demonstrates that a new combination of treatments for stroke due to intracerebral haemorrhage (ICH) significantly improves the chances of favourable outcomes and reduces deaths by one in every 35 patients. The results are important for low- and middle-income countries like South Africa, as the proportion of ICH is much higher in such countries.

The INTERACT3 study is the first-ever randomised controlled trial to show a clearly positive outcome for the treatment of ICH. Timely administration of the new Care Bundle centred on rapid hypertension control, led to improved recovery, lower rates of death, and better overall quality of life in ICH patients. The findings were presented at the European Stroke Organisation Conference in Munich, Germany, and simultaneously published in The Lancet.

Professor Craig Anderson, Director of Global Brain Health at The George Institute and a senior author of the research said, “Despite the high rates of ICH and its severity, there are few proven options for treating it, but early control of high blood pressure is the most promising. Time is critical when treating this type of stroke, so we tested a combination of interventions to rapidly stabilise the condition of these patients to improve their outcomes. We estimate that if this protocol was universally adopted, it could save tens of thousands of lives each year around the world.”

In the INTERACT3 study, over 7000 patients were enrolled across 144 hospitals in 10 countries – nine middle-income countries and one high-income country. The research team evaluated the effectiveness of the new Care Bundle, which included early intensive lowering of systolic blood pressure, strict glucose control, fever treatment, and rapid reversal of abnormal anticoagulation.

They found that using this new treatment protocol compared to usual care reduced the likelihood of a poor functional outcome, including death, after six months. This was estimated to prevent one additional death for every 35 patients treated.

Central to this was a rapid reduction in systolic blood pressure, where target levels were achieved, on average, in 2.3 hours [range 0.8 to 8.0hrs], compared to 4.0 hours [range 1.9 to 16.0hrs] in the control group. The interventional protocol resulted in a statistically significant reduction in mortality, number of serious adverse events, and time spent in hospital, as well as demonstrating an improvement in health-related quality of life.

 Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16.0% vs 20.1%).

The burden of ICH is greatest in low- and middle-income countries. In 2019, 30% of all stroke cases in LMICs were ICH, almost double the proportion seen in high-income countries (16%). This is in part due to high rates of hypertension and limited resources for primary prevention strategies, including identification and management of stroke risk factors by healthcare services.

Dr Lili Song, joint lead author and Head of the Stroke Program at The George Institute China, said, “A lack of proven treatments for ICH has led to a pessimistic view that not much can be done for these patients. However, with INTERACT3, we demonstrate on a large scale how readily available treatments can be used to improve outcomes in resource-limited settings. We hope this evidence will inform clinical practice guidelines across the globe and help save many lives.”

Source: George Institute for Global Health

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Gauteng Cholera Deaths Rise as Government Sets up Field Hospital

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As of Sunday, reports indicate that 23 people have died so far in the recent cholera outbreak in Hammanskraal, a direct result of the town’s neglected water sanitation infrastructure. A further 48 have been hospitalised, with six emergency field tents being set up to prop up the overburdened Jubilee Hospital, which has seen 215 patients since 19 May, as reported in the most recent Gauteng Department of Health bulletin.

The temporary field hospital has been set up to immediately attend to cases of dehydration, supplying oral rehydration solution (IRS) as well as intravenous fluids. More critical patients are taken to Tshwane hospitals.

The Gauteng Department of Health also notes that as of Friday, 27 of the 75 confirmed cholera cases had recovered and been discharged. The Gauteng Department of Education has said that it will intensify efforts to supply schools in Hammanskraal with clean drinking water.

South Africa’s most serious outbreak of cholera in recent history was from November 2008, when a massive cholera outbreak occurred in Zimbabwe and spread to South Africa. Within the first 5 months of the outbreak, more than 73 000 cases and 3500 deaths (case fatality rate of >4.7%) had been reported, and it spread to South Africa through Musina. Between 15 November 2008 and 30 April 2009, a total of 12 706 cases of cholera were reported by the National Department of Health. Of the total number of cases, 1114 (9.0%) were laboratory-confirmed cases, and 65 deaths (case fatality rate of 0.5%) were recorded. In this outbreak, microbial analysis published in the Journal of Infectious Diseases found the emergence of antimicrobial resistance in Vibrio cholerae 01 strains.

The National Institute of Communicable Diseases has posted guidelines [PDF] for the management of suspected cholera chases.