Effect of high-dose intravenous ascorbic acid on microcirculation and endothelial glycocalyx during sepsis and septic shock: a double-blind, randomized, placebo-controlled study.

Previous studies indicate supplemental vitamin C improves microcirculation and reduces glycocalyx shedding in septic animals. Our randomized, double-blind, placebo-controlled trial aimed to investigate whether a high dose of intravenous ascorbic acid (AA) might improve microcirculation and affect glycocalyx in septic patients. In our study, 23 septic patients were supplemented with a high dose (50 mg/kg every 6 h) of intravenous AA or placebo for 96 h. Sublingual microcirculation was examined using a handheld Cytocam-incident dark field (IDF) video microscope. A sidestream dark field video microscope (SDF), connected to the GlycoCheck software (GlycoCheck ICU®; Maastricht University Medical Center, Maastricht, the Netherlands), was employed to observe glycocalyx. We found a significantly higher proportion of perfused small vessels (PPV) 6 h after the beginning of the trial in the experimental group compared with placebo. As an indicator of glycocalyx thickness, the perfused boundary region was lower in capillaries of the 5-9 µm diameter in the AA group than placebo after the first dose of AA. Our data suggest that high-dose parenteral AA tends to improve microcirculation and glycocalyx in the early period of septic shock. The study was retrospectively registered in the clinicaltrials.gov database on 26/02/2021 (registration number NCT04773717).

Alterations of retinal vessels in patients with sepsis.

To compare the retinal vasculature of septic patients with age-matched healthy volunteers. This is a single-centre prospective observational study from January 2018 to May 2019 in a third-level ICU. We performed a single fundus imaging using a hand-held digital fundus camera in patients with sepsis or septic shock (n = 40) during the first 24 h after ICU admission and compared these data with age-matched healthy controls (n  =  20). Semi-automated image analysis was performed. The average retinal arteriolar and venular caliber were calculated and summarized as the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Arteriole:venular ratio (AVR) was defined as the ratio of CRAE:CRVE. The vascular length density of segmented retinal vessels was = defined as the skeletonized vessel area/total area × 100%. Median CRAE of septic patients was significantly higher in comparison to healthy controls (165[149-187] vs. 146[142-158] µm, p = 0.002). However, median CRVE and AVR of septic patients did not differ with healthy controls (247[223-282] vs. 244[215-272], p = 0.396 and 0.64[0.58-0.74] vs. 0.61[0.55-0.68], p = 0.145) respectively. Patients with sepsis showed a significant decrease in retinal vascular length density compared with healthy subjects (p < 0.001). Retinal observation using a hand-held fundus imaging device showed signs of arteriolar vasodilation with decreased vascular density in septic patients in comparison to healthy controls.

Effects of whole body heat stress on sublingual microcirculation in healthy humans.

PURPOSE: To assess the effect of whole body heat stress on sublingual microcirculation. METHODS: Fourteen apparently healthy subjects participated in the study. Passive body heating was performed by immersing the subjects up to the waist in a water bath at 44 °C continuously until a rectally obtained core temperature of 39.5 °C was reached. Systemic hemodynamic parameters and sublingual microcirculation were evaluated and recorded before heating, immediately after heating, and 1 h after heating. RESULTS: The subjects showed very high physiological stress and significantly increased noradrenaline and prolactin concentrations in the blood. Whole body heating resulted in significantly increased oxygen uptake, heart rate, and cardiac output. One hour after heating, heart rate remained increased, but cardiac output almost returned to baseline. Mean arterial pressure significantly decreased after heating and remained decreased for at least 1 h. There was no significant difference in the microvascular flow index and proportion of perfused vessels of small vessels at the end of heating and 1 h after heating, in comparison with baseline variables. However, functional capillary density and total vessel density of small vessels significantly increased at the end of heating (10.8 ± 2.4 vs. 11.7 ± 2.0 1/mm and 19.5 ± 3.5 vs. 22.2 ± 3.3 mm/mm(2), p < 0.05, respectively) and remained increased 1 h after heating. CONCLUSION: Whole body heat stress increases sublingual functional capillary density, oxygen consumption, and cardiac output.

Microcirculatory effects of L-arginine during acute anaerobic exercise in healthy men: A pilot study.

BACKGROUND/OBJECTIVE: We hypothesized that L-arginine supplementation increases sublingual capillary perfusion during acute anaerobic exercise. METHODS: In a double-blind randomized study, 20 healthy men were randomly assigned to an L-arginine group or a placebo group. Both groups performed a standard 60-second duration BOSCO jumping test. Before the exercise, immediately after, and 30 minutes after exercise, systemic hemodynamic parameters were recorded. Sublingual evaluation of microcirculation using sidestream dark field (SDF) videomicroscopy was also carried out. RESULTS: There were no differences in mean arterial blood pressure and cardiac output between the placebo and L-arginine groups immediately after exercise and at 30 minutes after exercise. Both groups had no changes in the microvascular flow index and proportion of perfused vessels of small vessels over the testing period. We observed significantly higher functional capillary density [14.1 (12.5 - 16.0) vs. 11.7 (10.9 - 12.9) 1/mm, p = 0.021] and total vessel density of small vessels [27.8 (24.4 - 29.2) vs. 23.0 (21.6 - 24.2) mm/mm2, p = 0.041] in the L-arginine group compared with the placebo group immediately after exercise, but after 30 minutes these differences had disappeared. CONCLUSION: Our findings show that supplementation with L-arginine may cause additional effects on the acute anaerobic exercise-induced transient increase in capillary density in the sublingual mucosa of untrained men.

New formula herbal pellets demonstrate a uniform and stable release of the active ingredients in vitro.

The aim of this study was to evaluate the effect of different capsule filling manufacturing techniques and storage conditions on the release of the active ingredients from herbal capsules during the dissolution test in vitro. Different techniques for the preparation of the original mixture of dry extracts were applied, and subsequently capsules with six different fillings were prepared. The stability of the capsules was evaluated in different long-term storage conditions, registering changes in the water content (loss of drying), capsule disintegration time, and phenolic compounds dissolution test in vitro. The baseline of phenolic compounds release in the control capsules (filled with the mixture of the powder of dry herbal extracts) was the highest, compared to other capsule groups, yet during long-term storage, these capsules accumulated too much moisture, which impeded capsule disintegration time and phenolic compounds release. The study showed that moisture and temperature changes occurring during the storage of the preparation had a negative effect on the release of phenolic compounds from herbal capsules. Capsules filled with pellets demonstrated a uniform and stable release of the active ingredients in different long-term storage conditions, which indicates that the manufacturing technology of dry herbal extracts affects the stability of the active ingredients.

Differences in Hemodynamic Response to Passive Leg Raising Tests during the Day in Healthy Individuals: The Question of Normovolemia.

BACKGROUND: The passive leg-raising (PLR) test was developed to predict fluid responsiveness and reduce fluid overload. However, the hemodynamic response of healthy individuals to the PLR test and how it changes during the day, between the morning and evening, after individuals have consumed food and fluids, has not been profoundly explored. This study aimed to compare the systemic hemodynamic changes in healthy individuals between morning and evening PLR tests. METHODS: In this study, the PLR test was performed twice a day. The first PLR test was performed between 08h00 and 09h00 in the morning, while the second PLR test was performed between 20h00 and 21h00 in the evening. Hemodynamic parameters were measured using an impedance cardiography monitor, and a cutoff value of a 10% increase in stroke volume (SV) during the PLR test was used to differentiate between preload responders and non-responders. RESULTS: We included 50 healthy volunteers in this study. When comparing the morning and evening PLR test results, we found no PLR-induced differences in heart rate (-3 [-8-2] vs. -2 [-8-4] beats/min, p = 0.870), SV (11 [5-22] vs. 12 [4-20] mL, p = 0.853) or cardiac output (0.7 [0.2-1.3] vs. 0.8 [0.1-1.4] L/min, p = 0.639). We also observed no differences in the proportion of preload responders during the PLR test between the morning and evening (64% vs. 66%, p = 0.99). However, there was a moderate agreement between the two PLR tests (morning and evening) (kappa = 0.429, p = 0.012). There was a moderate correlation between the changes in SV between the two PLR tests (rs = 0.50, p < 0.001). CONCLUSION: In young, healthy individuals, we observed no change in the systemic hemodynamic responsiveness to the PLR test between the morning and evening, without restriction of fluid and food intake.

Ethnopharmacology for Skin Diseases and Cosmetics during the COVID-19 Pandemic in Lithuania.

The documentation of ethnopharmaceutical knowledge has always been important for the preservation of countries' cultural, social, and economic identity. The COVID-19 pandemic with the collapse of healthcare, which has left the individual health to self-care, has also forced us to look back at ethnopharmacology from a practical point of view. This is the first study in Lithuania, dedicated entirely to ethnopharmaceuticals used for skin diseases and cosmetics, and the first study to analyse ethnopharmacology as a Lithuanian phenomenon during the ongoing COVID-19 pandemic. The main purpose of this study was to collect and evaluate ethnopharmaceutical knowledge regarding skin diseases and cosmetics in Siauliai District, Lithuania during the COVID-19 pandemic from July 2020 to October 2021. This study surveyed 50 respondents; the survey was conducted using the deep interview method. The respondents mentioned 67 species of medicinal plants from 37 different families used for skin diseases (64.18%), cosmetics (13.44%) and cosmeceuticals (22.38%). Of the 67 plant species, 43 (64%) were not included in the European Medicines Agency monographs and only 14 species (21%) of all included species were used with European Medicines Agency approved medical indications for skin diseases. In terms of public health, the safety of "self-treatment" and recovery rituals for skin diseases are no less important than ethnopharmacological knowledge and its application, this being especially relevant during the COVID-19 pandemic.

Herbal Medicine Uses for Respiratory System Disorders and Possible Trends in New Herbal Medicinal Recipes during COVID-19 in Pasvalys District, Lithuania.

Despite some preliminary studies of the available herbal medicine preparations and their curative effects on COVID-19, experts still fear that unproper use of such homemade medicines could do more harm than good to people relying on unproven alternatives of questionable efficacy. The main purpose of this study was to evaluate the safety of herbal medicines used for respiratory system disorders in the Pasvalys district during the COVID-19 pandemic in Lithuania. An archival source was also studied, looking for possible recipes for the treatment and prevention of respiratory diseases in Lithuanian traditional medicine, emphasizing the safety guidelines. The survey was conducted using the deep interview method. The respondents mentioned 60 species of medicinal plants from 29 different families used for the treatment and prevention of respiratory system disorders (for cough mostly, 51.70% of all indications). Twenty eight out of 60 plant species were not included in the European Medicines Agency monographs and only 50% of all included species were used as indicated by the European Medicines Agency for respiratory system disorders. The trends in the ethnopharmacological choices of modern consumers and the analysis of archival sources can be a great source of ideas for new herbal-based pharmaceutical preparations for COVID-19 symptoms in Lithuania considering the safety recommendations.

Ocular microvascular changes in patients with sepsis: a prospective observational study.

BACKGROUND: The aim of the study was to detect differences in the conjunctival microcirculation between septic patients and healthy subjects and to evaluate the course of conjunctival and retinal microvasculature in survivors and non-survivors over a 24-h period of time. METHODS: This single-center prospective observational study was performed in mixed ICU in a tertiary teaching hospital. We included patients with sepsis or septic shock within the first 24 h after ICU admission. Conjunctival imaging, using an IDF video microscope, and retinal imaging, using portable digital fundus camera, as well as systemic hemodynamic measurements, were performed at three time points: at baseline, 6 h and 24 h. Baseline conjunctival microcirculatory parameters were compared with healthy controls. RESULTS: A total of 48 patients were included in the final assessment and analysis. Median APACHE II and SOFA scores were 16[12-21] and 10[7-12], respectively. Forty-four (92%) patients were in septic shock, 48 (100%) required mechanical ventilation. 19 (40%) patients were discharged alive from the intensive care unit. We found significant reductions in all microcirculatory parameters in the conjunctiva when comparing septic and healthy subjects. In addition, we observed a significant lower microvascular flow index (MFI) of small conjunctival vessels during all three time points in non-survivors compared with survivors. However, retinal arteriolar vessels were not different between survivors and non-survivors. CONCLUSIONS: Conjunctival microvascular blood flow was altered in septic patients. In the 24-h observation period conjunctival small vessels had a significantly higher MFI, but no difference in retinal arteriolar diameter in survivors in comparison with non-survivors. Trial registration NCT04214743, https://www.clinicaltrials.gov. Date of registration: 31 December 2019 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04214743.

Modulation of Endothelial Glycocalyx and Microcirculation in Healthy Young Men during High-Intensity Sprint Interval Cycling-Exercise by Supplementation with Pomegranate Extract. A Randomized Controlled Trial.

The natural components of the pomegranate fruit may provide additional benefits for endothelial function and microcirculation. It was hypothesized that supplementation with pomegranate extract might improve glycocalyx properties and microcirculation during acute high-intensity sprint interval cycling exercise. Eighteen healthy and recreationally active male volunteers 22-28 years of age were recruited randomly to the experimental and control groups. The experimental group was supplemented with pomegranate extract 20 mL (720 mg phenolic compounds) for two weeks. At the beginning and end of the study, the participants completed a high-intensity sprint interval cycling-exercise protocol. The microcirculation flow and density parameters, glycocalyx markers, systemic hemodynamics, lactate, and glucose concentration were evaluated before and after the initial and repeated (after 2 weeks supplementation) exercise bouts. There were no significant differences in the microcirculation or glycocalyx over the course of the study (p < 0.05). The lactate concentration was significantly higher in both groups after the initial and repeated exercise bouts, and were significantly higher in the experimental group compared to the control group after the repeated bout: 13.2 (11.9-14.8) vs. 10.3 (9.3-12.7) mmol/L, p = 0.017. Two weeks of supplementation with pomegranate extract does not influence changes in the microcirculation and glycocalyx during acute high-intensity sprint interval cycling-exercise. Although an unexplained rise in blood lactate concentration was observed.

Ethnobotanical Study of Cultivated Plants in Kaisiadorys District, Lithuania: Possible Trends for New Herbal Based Medicines.

BACKGROUND: Despite the growing body of ethnobotanical studies in Europe, publications are scarce in Lithuania. Ethnobotanical study in Kaisiadorys district is one of the few from this field done in Lithuania. Lithuania is divided into five ethnographic regions, and Kaisiadorys district is an area which borders with the three of them (Aukstaitija, Dzukija, and Suvalkija), which determines the ethnographic distinctiveness of the area. The aim of this study was to determine the occurrence of cultivated medicinal plants, their families and pharmaceutical forms used in Kaisiadorys district, Lithuania, and to assess the conformity of medicinal plant materials used by respondents with the recommendations for medicinal plant materials in the World Health Organization monographs. METHODS: The field work was conducted in periods of time from July 2016 to October 2017. During this ethnobotanical research, 30 people were interviewed, 25 of whom agreed to communicate. The average age of respondents was 65 years. Information was collected using semistructured and structured interviews. The obtained information was recorded indicating ethnic names of plants, their preparation techniques, parts used, modes of administration, and application for therapeutic purposes. RESULTS: Respondents mentioned 71 species of cultivated medicinal plants from 38 families, used for therapeutic purposes and indicated which parts of the plant they use, how they prepare them, indications for use, and ways of administration. The most commonly cited families were Asteraceae (20.5%), Lamiaceae (13.9%), and Apiaceae (12.8%); most popular plants, cited more than 20 times, were Tilia cordata L., Matricaria recutita L., Calendula officinalis L., Carum carvi L., and Artemisia absinthium L. The frequently used plant parts were flowers (mentioned 35.8%), leaves (16.3%), roots and tubers (16.1%), herb (14.8%), and seeds (7.0%). Diseases most frequently treated were digestive (21.5% of citations), respiratory (21.3 % of citations), mental and behavioral (11.0%) disorders, certain infections and parasitic diseases (10.1%), and diseases of genitourinary system (9.1%). CONCLUSIONS: Only 19 of the cultivated medicinal plant species mentioned by interviewed persons are described in the World Health Organization monographs. This means that the remaining 52 species are used without the World Health Organization approved medical indications, based solely on the folk medicine knowledge and experience. This study showed that the folk use of plants is strongly rooted in daily practice in the studied area.

Ethnopharmaceutical knowledge in Samogitia region of Lithuania: where old traditions overlap with modern medicine.

BACKGROUND: Modern ethnopharmaceutical studies are still quite unusual in Northern Europe. Data regarding the medicinal use of plants, animals, and fungi and also of spiritual rituals of healing is obtained mostly from ethnographic and folkloric sources in Lithuania. The aim of this study was to assess the ethnopharmaceutical knowledge regarding traditional use of natural substances for medicinal purposes in the Samogitia region and compare with prior research conducted 10 years prior in the same region. METHODS: The study was performed during 2016-2017 in the Samogitia region (Lithuania) using the conventional technique of ethnobotanical studies. Twenty-eight respondents aged between 50 and 92 years were selected for the study using snowball techniques. Information was collected using semi-structured and structured interviews. The obtained information was recorded indicating local names of plants, their preparation techniques, parts used, modes of administration, and application for therapeutic purposes. RESULTS: During the research, 125 records of raw materials of herbal origin belonging to 55 families were made. The Asteraceae family had the highest number of references, 147 (16.6%). It was stated that the most commonly used medicinal plants were the raspberry (Rubus idaeus L.) (100%), marigold (Calendula officinalis L.) (96.4%), camomile (Matricaria recutita L.) (92.9%), and small linden tree (Tilia cordata Mill.) (92.9%). The most commonly used material of animal origin was the toad (Bufo bufo) (89%). The most commonly used kind of fungi was the common stinkhorn (Phallus impudicus) (71%), and the material of the mineral origin was sand (50%). Comparative analysis of the two surveys in this region showed similar results and produced a large amount of ethnopharmaceutical information. CONCLUSIONS: Lithuania belongs to the countries known for urban ethnobotany where old traditions overlap with modern healing methods. Also, because modern medical assistance is quite expensive, self-medication with home-made medicines is still popular in Lithuania. It is important to collect and systematize this information as soon as possible, to save it as a traditional Lithuanian heritage and also use it for scientific investigations.

Time Evolution of Sublingual Microcirculatory Changes in Recreational Marathon Runners.

We aimed to evaluate changes in sublingual microcirculation induced by a marathon race. Thirteen healthy male controls and 13 male marathon runners volunteered for the study. We performed sublingual microcirculation, using a Cytocam-IDF device (Braedius Medical, Huizen, Netherlands), and systemic hemodynamic measurements four times: 24 hours prior to their participation in the Kaunas Marathon (distance: 41.2 km), directly after finishing the marathon, 24 hours after the marathon, and one week after the marathon. The marathon runners exhibited a higher functional capillary density (FCD) and total vascular density of small vessels at the first visit compared with the controls. Overall, we did not find any changes in sublingual microcirculation of the marathon runners at any of the other visits. However, in a subgroup of marathon runners with a decreased FCD compared to the subgroup with increased FCD, the subgroup with decreased FCD had shorter running time (190.37 ± 30.2 versus 221.80 ± 23.4 min, p = 0.045), ingested less fluids (907 ± 615 versus 1950 ± 488 mL, p = 0.007) during the race, and lost much more weight (-2.4 ± 1.3 versus -1.0 ± 0.8 kg, p = 0.041). Recreational marathon running is not associated with an alteration of sublingual microcirculation. However, faster running and dehydration may be crucial for further impairing microcirculation.

Ethnomedicinal Uses of Honeybee Products in Lithuania: The First Analysis of Archival Sources.

Lithuania has old ethnomedicine traditions, consisting of many recipes with herbal, animal, and mineral original ingredients. All these findings were mostly collected in Lithuanian language, often in local community's dialects, and stored only in archives. We analyzed archival sources about honeybee and its products used for medicinal purposes dated from 1886 till 1992 in different parts of Lithuania. We systematized and presented the most important information about bees and their products: indication for usage, ingredients used in the recipe, their preparation techniques, and application for therapeutic purposes. Researchers in Lithuania are now looking for new evidence based indications and preparation and standardization methods of bee products. Archival sources are a foundation for studies in Lithuania. The results can be integrated into scientifically approved folk medicine practices into today's healthcare.