Lung Microbiota: Its Relationship to Respiratory System Diseases and Approaches for Lung-Targeted Probiotic Bacteria Delivery

Really interesting topic and paper (well illustrated too).

Eat more kimchi!

Source:

https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.3c00323

Abstract

Microorganisms that make up the local microbiota (such as Lactobacillus sp. and Bifidobacteriumsp.) play a crucial role in the modulation of diseases and health states by taking place not only in the gut but also in many parts of our body. There is also interference between the gut and the lung via the gut–lung axis. The relationship between respiratory diseases and lung microbiota, which become more of an issue of particular importance in recent years, shows that probiotics play an essential role in maintaining the balance of microorganisms in the respiratory tract. However, studies on probiotics’ prophylactic or therapeutic application in chronic lung diseases are limited. In this review, the literature between 1977 and 2022 was surveyed. General information about human microbiota was accessed in earlier sources, and especially in the past decade, research on lung microbiota has been reached. The relationship between lung microbiota and important respiratory diseases such as bronchopulmonary dysplasia, chronic obstructive pulmonary disease, pneumonia, cystic fibrosis, allergy-asthma, influenza, lung cancer, and COVID-19 infection, was scrutinized after mentioning human microbiota, the gut–lung axis, and respiratory tract microbiota. The mechanism of action of probiotics and the formulation approaches of probiotics in terms of pharmaceutical technology were reviewed. Finally, future perspectives on lung-targeted administration of probiotic bacteria with prophylactic or therapeutic potential, or both, were presented.

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Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease

A typical silly research paper title:

The point the authors are making is sildefanil and such compounds (ViagraR etc.) may be protective against Alzheimer Disease-type neurodegeneration. Or is it that the desire for, and frequency of intercourse are protective? 

Source: https://www.neurology.org/doi/full/10.1212/WNL.0000000000209131

Either way, this is one of the more interesting drug explorations in the world of “dementia drugs”. And repurposing a compound adds years of post-marketing surveillance.

 

 

 

 

 

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Tamsulosin and the risk of dementia in older men with benign prostatic hyperplasia

 
Comparative Study

 

2018 Mar;27(3):340-348.

 doi: 10.1002/pds.4361. Epub 2018 Jan 9.

Tamsulosin and the risk of dementia in older men with benign prostatic hyperplasia

 
Affiliations 

Abstract

Purpose: Clinicians use tamsulosin, an α1-adrenoceptor antagonist, to manage symptomatic benign prostatic hyperplasia (BPH). Because α1-adrenoceptors are also present in the brain, the potential exists for adverse effects on cognitive functions. We explored the association between tamsulosin use and dementia risk.

Methods: We used Medicare data (2006-2012) to conduct a cohort study among patients aged ≥65 years and diagnosed with BPH. Men taking tamsulosin (n = 253 136) were matched at a 1:1 ratio using propensity-scores to each of 6 comparison cohorts: patients who used no BPH-medication (n = 180 926), and patients who used the following alternative-BPH-medications: doxazosin (n = 28 581), terazosin (n = 23 858), alfuzosin (n = 17 934), dutasteride (n = 34 027), and finasteride (n = 38 767). Assessment began following the first fill of BPH-medication to identify incident dementia by ICD-9 diagnosis codes. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for dementia using Cox proportional hazard regression for each of the 6 propensity-score-matched cohort-pairs.

Results: The median follow-up period for all cohorts was 19.8 months. After propensity-score matching, the tamsulosin cohort had an incidence of dementia of 31.3/1000 person-years compared with only 25.9/1000 person-years in the no-BPH-medication cohort. The risk of dementia was significantly higher in the tamsulosin cohort, when compared with the no-BPH-medication cohort (HR [95% CI]: 1.17 [1.14, 1.21]) and each of the alternative-BPH-medication cohorts: doxazosin (1.20 [1.12, 1.28]), terazosin (1.11 [1.04, 1.19]), alfuzosin (1.12 [1.03, 1.22]), dutasteride (1.26 [1.19, 1.34]), and finasteride (1.13 [1.07, 1.19]). The significance of these findings persisted in sensitivity analyses.

Conclusion: Tamsulosin may increase the risk of dementia in older men with BPH.

Keywords: benign prostatic hyperplasia; claims database; dementia; pharmacoepidemiology; propensity score matching; retrospective cohort study; tamsulosin.

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LED strobe lights clear Alzheimer plaques?

Integrative neuroscience…. A rare species indeed.

Very interesting and well written article on potential new treatments:

https://www.quantamagazine.org/stimulated-brain-waves-offer-a-possible-treatment-for-alzheimers-20200527/

 

 

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‘On-Demand’ Fast Mobilizes Fat; Low-Carb Breakfast Stymies Hunger – Medscape – Oct 12, 2020.

‘On-Demand’ Fast Mobilizes Fat; Low-Carb Breakfast Stymies Hunger – Medscape – Oct 12, 2020.

 

‘On-Demand’ Fast Mobilizes Fat; Low-Carb Breakfast Stymies Hunger

Becky McCall

October 12, 2020

Greater fat tissue mobilization can be achieved through early-day fasting in comparison to consuming a low-carbohydrate breakfast or a Mediterranean-style breakfast, shows a small study that explored the short-term effects of intermittent fasting by lean people.

 

The study also found that consumption of a low-carbohydrate breakfast results in longer suppression of hunger compared to a Mediterranean breakfast.

Dimitrios Tsilingiris, MD, PhD, led the study and presented the findings recently at the virtual meeting of the European Association for the Study of Diabetes (EASD).

“Through fasting intervals as short as those achievable through a 16:8 restricted feeding scheme, a substantially and measurably increased fat tissue mobilization ― as indexed by increased ketone body production ― may occur,” said Tsilingiris, reporting the main finding.

He added that for most ketogenic diets, time is needed for the switch toward fat burning, but the findings from this study could provide support for an “on-demand” application of this strategy.

“The quite high subjective hunger scores at the end of the fasting sessions should also be taken into account, since the feeling of hunger may obviously drive the subsequent caloric quantity intake,” Tsilingiris, formerly of Laiko General Hospital, Athens, Greece, but now based at the University Hospital Heidelberg, in Germany, pointed out.

Anne-Marie Aas, PhD, clinical dietitian and associate professor at Oslo University Hospital, Oslo, Norway, was session moderator. She told Medscape Medical News that she welcomed the study because there is a lack of human studies of the clinical implications of different forms of intermittent fasting.

“The findings from this Greek study in healthy people is interesting but not surprising, since a prolonged fast would naturally prolong the time the metabolism yields energy from fat stores,” she said.

“The most interesting finding is perhaps that fasting resulted in increased hunger, while the low-carb breakfast suppressed appetite for longer than the typical Mediterranean breakfast.” she said.

 

“This is in line with an earlier study from the same group [as reported from EASD 2018] showing that morning-time carbohydrate restriction resulted in greater weight loss in obese individuals over a 2-month period,” she noted.

 

First Study of Short-Term “On-Demand” Intermittent Fasting

Tsilingiris explained that evidence in the literature suggests that intermittent fasting is associated with numerous health benefits. The term refers to a relatively heterogeneous group of dietary habits that commonly include prolonged fasting intervals within a month (periodic fasting), a week (5:2, alternate day fasting), or a day (time-restricted feeding, 16:8).

 

In theory, intermittent fasting leads to loss of fat tissue through a metabolic milieu that promotes fat mobilization, he said.

 

“To our knowledge,” he said, “this hypothesis regarding the shortest-term application of intermittent fasting ― that is, the increasingly popular 16:8 ― has not been put to the test until now.”

 

He and his team investigated early-day fasting for adipose tissue mobilization, as indicated by β-hydroxybutyrate levels, and they compared this approach with two different kinds of breakfast.

 

“We compared the ketogenic response of [early-day] fasting to that following a zero-carb and a standard Mediterranean breakfast,” Tsilingiris said.

 

The crossover study included 10 normal-weight (body mass index [ΒΜI] < 25 kg/m2) healthy individuals.

 

In the study, participants had dinner at 8:00 PM. The following morning, they either had breakfast or they fasted from 8:00 AM to 2:00 PM.

 

Breakfasts consisted of either a Mediterranean breakfast (500 kcal of 50% carbohydrate, 30% fat, 20% protein) or a zero-carbohydrate breakfast (500 kcal, 60% fat, 40% protein).

 

The sessions were held at least 1 week apart but no more than 3 weeks apart. All participants had identical dinners on the preceding evening.

 

Early Day Fasting Shows Highest Fat Mobilization

Insulin levels were lower and mobilization of fat tissue was greater (highest beta-hydroxybutyrate levels) when the participants were fasting intermittently in comparison to when they were having breakfast (either zero-carbohydrate or Mediterranean style).

 

When fasting, the adjusted area under the curve representing β-hydroxybutyrate concentration was 6.17 mmolh/L. By contrast, it was 4.16 mmolh/L after the zero-carbohydrate breakfast and 3.65 mmolh/L after the Mediterranean breakfast, when adjusted for fasting duration HOMA-R and triglyceride/HDL ratio.

 

Factors found to be associated with fat mobilization were fasting duration (P = .040), BMI (= .020), and insulin resistance (HOMA-R; P = .059).

 

For the individuals who had breakfast, there were no differences in ketone body levels and beta-hydroxybutyrate levels, regardless of the type of breakfast they had.

 

Low-Carb Breakfast Staved Off Hunger for Longer

However, there was a difference in hunger score regarding the two breakfasts.

 

“The fasting state was associated with high subjective hunger scores, while a more durable hunger suppression was achieved after the low-carb breakfast intake compared to the Mediterranean breakfast,” reported Tsilingiris.

 

In the late postprandial stage (3 – 6 hours after eating), measures of hunger on the visual analogue scale were 16.0, 7.5, and 12.0 for fasting, zero-carbohydrate breakfast, and Mediterranean breakfast, respectively.

 

There was a small but significant difference in insulin levels across all three groups.

 

Insulin levels were “quite a lot higher in the Mediterranean compared to the low-carbohydrate breakfast, but that did not translate to a measurable difference in ketone body production between the two approaches,” Tsilingiris explained.

 

He speculated on why this might be the case: “It doesn’t take a whole lot of insulin to inhibit ketogenesis and/or lipolysis among lean, apparently metabolic healthy individuals.”

 

There are undoubtedly “many other regulators ― for example, hormonal, rather than just insulin, that play a role in the modulation of the studied effects ― that we did not take into account in the current study and could have influenced these observations,” he noted.

 

In a comment, Aas pointed out, “Another study presented at another EASD session [Krista Varady, University of Illinois: Clinical Application of Intermittent Fasting] showed that similar interventions over 3 months resulted in an unintentional decrease in calorie intake of approximately 500 kcal/d, weight reduction, and improvements in several metabolic risk factors.”

 

Tsilingiris and Aas have disclosed no relevant financial relationships.

 

European Association for the Study of Diabetes (EASD) 2020 Annual Meeting: Presented September 24, 2020.

 

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