Combining topical dermal infused exosomes with injected calcium hydroxylapatite for enhanced tissue biostimulation.

BACKGROUND: Exosome research continues to flourish. Subsequent knowledge surrounding indications, dose-response, safety, efficacy, and the ability to combine exosome treatment as a "skin primer"-for biostimulation modalities such as calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and platelet-rich fibrin matrix (PRFM) is growing rapidly. The objective of this study was to develop safe, reproducible methods of improving topical exosome absorption to enhance the quality of skin either by themselves, or in combination with injectable CaHA. METHODS: Under IRB Approval (International Cell Surgical Society: ICSS-2022-007), 40 patients were enrolled in this study. Twenty patients underwent facial biostimulatory dermal infusion alone, to determine if this method allowed adequate exosome absorption. Five patients underwent facial biostimulatory infusion followed immediately by Dilute CaHA injection (1:1 dilution) to the face. Five patients underwent exosome biostimulatory dermal infusion followed immediately by hyperdilute CaHA (dilution 1:4) injection to the neck. Five patients underwent Facial Dilute CaHA injection (1:1 dilution) alone, without dermal infusion. Five patients underwent neck hyperdilute CaHA injection (1:4 dilution) alone, without dermal infusion. All patients had pretreatment Quantificare 3-D photo-documentation and skin analysis (Quantificare, France). In all patients, the skin was first cleansed with a gentle glycolic acid facial wash (Gregory MD). To induce a "homing inflammatory environment" for the exosomes, sea salt exfoliation was performed (SaltFacial®, SaltMed, Cardiff, CA). A nitric oxide-generating serum (N101 Pneuma Nitric Oxide, Austin, TX) was then applied to act as an enhanced vehicle for absorption. A 3 MHz ultrasound (SaltFacial®, SaltMed, Cardiff, CA) was then utilized to further deepen the absorption of the nitric oxide serum. A topical emulsion containing equal volumes (1.0 cc containing 1 million) of exosomes (Kimera Labs, Miramar, FL), 25 units of botulinum toxin (Xeomin, Merz Aesthetics, Raleigh, NC) and hyaluronic acid (Belatero, Merz Aesthetics, Raleigh, NC) was mixed via back-and-forth propulsion in a 3-cc syringe. When adequately mixed, the emulsion was then applied to the treatment areas. The cavitating ultrasound was then used to aid in the absorption of the emulsion. The patients were then treated with high-intensity LED therapy (SaltFacial®, SaltMed, Cardiff, CA), utilizing the collagen restoration preset program of combination red (660 nm) near-infrared (930 nm) wavelength for 20 min. Post-treatment Quantificare analysis was performed at 15 and 30 days after treatment. RESULTS: Without exception, all dermal infusion alone and CaHA injection alone patients showed an improvement in the tone, quality, and texture of their skin. Quantificare results showed consistent improvement in wrinkles, pores, skin evenness, improved vascularity, and a reduction in oiliness and unwanted pigment. When employed as a skin primer prior to injections (CaHA), enhanced and more rapid results were seen. CONCLUSIONS: Biostimulatory dermal infusion can be achieved utilizing topical placental mesenchymal stem cell-derived exosomes. These exosomes can be used alone, or mixed with ancillary ingredients such as botulinum toxin, hyaluronic acid dermal filler, and CaHA to customize and personalize treatments based upon individual patient needs. Topical absorption is enhanced with sea salt exfoliation, a topical nitric oxide-generating serum, and 3 MHz cavitating ultrasound. Post-absorption activity is enhanced with high-intensity LED treatment. The addition of CaHA injections after the topical exosome "priming of the skin" yielded enhanced skin quality faster than exosomes or CaHA alone.

Impact of salt and exogenous AM inoculation on indigenous microbial community structure in the rhizosphere of dioecious plant, Populus cathayana.

The sex-specific physical and biochemical responses in dioecious plants to abiotic stresses could result in gender imbalance, and how to ease the current situation by microorganisms is still unclear. Using native soil where poplars were grown, growth parameters, soil physicochemical properties in the rhizosphere soil of different sexes of Populus cathayana exposed to salt stress and exogenous arbuscular mycorrhizal (AM) inoculation were tested. Besides, the sex-specific microbial community structures in the rhizosphere soil of different sexes of Populus cathayana were compared under salt stress. To identify the sex-specific microbial community characteristics related to salinity and AM symbiosis, a combined qPCR and DGGE method was used to monitor microbial community diversity. Seedlings suffered severe pressure by salt stress, reflected in limited growth, biomass, and nutrient element accumulation, especially on females. Exogenous AM inoculation treatment alleviated these negative effects, especially under salt treatment of 75 mM. Compared with salt effect, exogenous AM inoculation treatment showed a greater effect on soil physical-chemical properties of both sexes. Based on DGGE results, salt stress negatively affected fungal richness but positively affected fungal Simpson diversity index, while exogenous AM inoculation treatment showed the opposite effect. Structural equation modeling (SEM) was performed to show the causal relationships between salt and exogenous AM inoculation treatments with biomass accumulation and microbial community: salt and exogenous AM inoculation treatment showed complicated effects on elementary concentrations, soil properties, which resulted in different relationship with biomass accumulation and microbial community. Salt stress had a negative effect on soil properties and microbial community structure in the rhizosphere soil of P. cathayana, whereas exogenous AM inoculation showed positive impacts on most of the soil physical-chemical properties and microbial community status.

Physical exercise prevents age-related heart dysfunction induced by high-salt intake and heart salt-specific overexpression in Drosophila.

A long-term high-salt intake (HSI) seems to accelerate cardiac aging and age-related diseases, but the molecular mechanism is still not entirely clear. Exercise is an effective way to delay cardiac aging. However, it remains unclear whether long-term exercise (LTE) can protect heart from aging induced by high-salt stress. In this study, heart CG2196(salt) specific overexpression (HSSO) and RNAi (HSSR) was constructed by using the UAS/hand-Gal4 system in Drosophila. Flies were given exercise and a high-salt diet intervention from 1 to 5 weeks of age. Results showed that HSSR and LTE remarkably prevented heart from accelerated age-related defects caused by HSI and HSSO, and these defects included a marked increase in heart period, arrhythmia index, malondialdehyde (MDA) level, salt expression, and dTOR expression, and a marked decrease in fractional shortening, SOD activity level, dFOXO expression, PGC-1α expression, and the number of mitochondria and myofibrils. The combination of HSSR and LTE could better protect the aging heart from the damage of HSI. Therefore, current evidences suggested that LTE resisted HSI-induced heart presenility via blocking CG2196(salt)/TOR/oxidative stress and activating dFOXO/PGC-1α. LTE also reversed heart presenility induced by cardiac-salt overexpression via activating dFOXO/PGC-1α and blocking TOR/oxidative stress.

Synthesis and Evaluation of 18F-Labeled Fluoroalkyl Triphenylphosphonium Salts as Mitochondrial Voltage Sensors in PET Myocardial Imaging.

We have previously reported that radiolabeled phosphonium cations accumulate in the mitochondria down a transmembrane potential gradient. We present an optimized procedure for synthesis of three [18F]-labeled fluoroalkyl triphenylphosphonium salts ([18F]FATPs) via two-step simple nucleophilic substitution reactions to develop new myocardial imaging agents for positron emission tomography (PET) . The total reaction time of [18F]FATPs was within 60 min, and the overall decay-corrected radiochemical yield was approximately 15-30% (decay corrected). Radiochemical purity was >98% according to analytical high-performance liquid chromatography (HPLC) . The specific activity of [18F]FATPs was >6.1 TBq/µmol. The [18F]FATPs exhibited higher first-pass extraction fraction values in isolated heart, higher uptake in the myocardium, and a more rapid clearance from the liver and lung than [13N]NH3 in normal rats. The images from rats with an occluded left coronary artery demonstrated sharply defined myocardial defects in the corresponding area of the myocardium. This imaging technology may enable high-throughput, multiple studies daily and wide distribution of PET myocardial studies in clinic.

Clemizole and La3+ salts ameliorate angiotensin II-induced glomerular hyperpermeability in vivo.

Angiotensin II (Ang II) induces marked, dynamic increases in the permeability of the glomerular filtration barrier (GFB) in rats. After binding to its receptor, Ang II elicits Ca2+ influx into cells, mediated by TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6). Clemizole and La3+ salts have been shown to block TRPC channels in vitro, and we therefore tested their potential effect on Ang II-induced glomerular hyperpermeability. Anesthetized male Sprague-Dawley rats were infused with Ang II (80 ng kg-1  min-1 ) alone, or together with clemizole or low-dose La3+ (activates TRPC5, blocks TRPC6) or high-dose La3+ (blocks both TRPC5 and TRPC6). Plasma and urine samples were taken during baseline and at 5 min after the start of the infusions and analyzed by high-performance size-exclusion chromatography for determination of glomerular sieving coefficients for Ficoll 10-80 Å (1-8 nm). Ang II infusion evoked glomerular hyperpermeability to large Ficolls (50-80 Å), which was ameliorated by clemizole, having no significant effect on glomerular filtration rate (GFR) or Ang II-mediated increase in mean arterial pressure (ΔMAP). In contrast, high- and low-dose La3+ significantly lowered ΔMAP and reduced Ang II-induced hyperpermeability. Combined, clemizole and low-dose La3+ were less effective at ameliorating Ang II-induced glomerular hyperpermeability than low-dose La3+ alone. In conclusion, our data show that both clemizole and La3+ are effective against Ang II-induced glomerular hyperpermeability, with differential effects on blood pressure. Further research using more specific blockers of TRPC5 and TRPC6 should be performed to reveal the underlying mechanisms.

Efficacy and Safety of Sea Salt-Derived Physiological Saline Nasal Spray as Add-On Therapy in Patients with Acute Upper Respiratory Infection: A Multicenter Retrospective Cohort Study.

BACKGROUND The purpose of this study was to assess the effects of seawater on nasal congestion and runny nose symptoms in adults with an acute upper respiratory infection (URI). MATERIAL AND METHODS This was a multicenter retrospective cohort trial of patients with acute URI and symptoms of nasal congestion and runny nose. The patients were assigned to 2 groups and were administered regular non-drug supportive treatment or supportive treatment with nasal irrigation with sea salt-derived physiological saline. The primary efficacy endpoint was the effective rate (percentage of patients with ≥30% symptom score reduction from baseline for nasal congestion and runny nose). RESULTS In total, 144 patients were enrolled, including 72 in each group, and 143 patients completed the study. Both groups had similar demographics and vital signs. The effective rates for nasal congestion and runny nose were significantly increased in the seawater group compared with patients in the control group (87.3% vs 59.7% for nasal congestion; 85.9% vs 61.1% for runny nose; both P<0.001). In addition, the 2 groups showed markedly different degrees of patient symptom score improvement in sleep quality and appetite (both P<0.01), but not in cough and fatigue (both P>0.05). There were no adverse events in either group. CONCLUSIONS The sea salt-derived physiological saline nasal spray device satisfactorily improved nasal congestion, runny nose, sleep quality, and appetite in adults with URI, with no adverse effects.

Safety and Efficacy of Sodium and Potassium Arachidonic Acid Salts in the Young Pig.

Arachidonic acid (ARA; 20:4n6) and docosahexaenoic acid (DHA; 22:6n3) are polyunsaturated fatty acids (FA) naturally present in breast milk and added to most North American infant formulas (IF). We investigated the safety and efficacy of novel sodium and potassium salts of arachidonic acid as bioequivalent to support tissue levels of ARA comparable to the parent oil; M. alpina oil (Na-ARA and K-ARA) and including a Na-DHA group. Pigs of both sexes were randomized to one of five dietary treatments (n = 16 per treatment; 8 male and 8 female) from postnatal day 2 to 23. ARA and DHA were included as either triglyceride (TG) or salt. Target dietary ARA/DHA concentrations as percent of total FA by weight were as follows: TT (0.47 TG/0.32 TG), NaT (0.47 Na-salt/0.32 TG), KT (0.47 K-salt/0.32 TG), and Na0 (0.47 Na-salt/0.00), NaNa (0.47 Na-salt/0.32 Na-salt). The primary outcome in this study was bioequivalence of ARA brain accretion. Growth performance; blood and tissue fatty acid levels; liver histology; complete blood cell counts; and serum chemistries were all evaluated. Overall, diets containing test sources of ARA and DHA did not affect growth performance; liver histology; or substantially influence hematological outcomes as compared with TT. The results confirm that the use of Na and K salt forms of ARA yield bioequivalent ARA accretion in the cerebral cortex and retinal tissue compared to TG-ARA. These findings confirm that use of Na-ARA and K-ARA salts in the young pig was safe and nutritionally bioequivalent to TG-ARA for critical neural tissues.

Fused isoselenazolium salts suppress breast cancer cell growth by dramatic increase in pyruvate-dependent mitochondrial ROS production.

The development of targeted drugs for the treatment of cancer remains an unmet medical need. This study was designed to investigate the mechanism underlying breast cancer cell growth suppression caused by fused isoselenazolium salts. The ability to suppress the proliferation of malignant and normal cells in vitro as well as the effect on NAD homeostasis (NAD+, NADH, and NMN levels), NAMPT inhibition and mitochondrial functionality were studied. The interactions of positively charged isoselenazolium salts with the negatively charged mitochondrial membrane model were assessed. Depending on the molecular structure, fused isoselenazolium salts display nanomolar to high micromolar cytotoxicities against MCF-7 and 4T1 breast tumor cell lines. The studied compounds altered NMN, NAD+, and NADH levels and the NAD+/NADH ratio. Mitochondrial functionality experiments showed that fused isoselenazolium salts inhibit pyruvate-dependent respiration but do not directly affect complex I of the electron transfer system. Moreover, the tested compounds induce an immediate dramatic increase in the production of reactive oxygen species. In addition, the isoselenazolothiazolium derivative selectively binds to cardiolipin in a liposomal model. Isoselenazolium salts may be a promising platform for the development of potent drug candidates for anticancer therapy that impact mitochondrial pyruvate-dependent metabolism in breast cancer cells.

Improving the iron status of school children through a school noon meal programme with meals prepared using a multiple micronutrient-fortified salt in Tamil Nadu, India.

BACKGROUND AND OBJECTIVES: To improve the iron status of school children through noon meals prepared using a multiple micronutrient-fortified salt. METHODS AND STUDY DESIGN: Children from a randomly selected school who consumed (intervention) and did not consume (reference) a noon meal prepared using a multiple micronutrient- fortified salt were studied over 1 year. A pre-post-test design for children aged 5-17years in reference (n=100) and intervention (n=128) groups was used. Levels of serum ferritin, soluble transferrin receptor (sTfR), alpha glycoprotein (AGP), and C-reactive protein (CRP) were assessed at baseline and at 1 year. In a subsample, urinary iodine was assessed. RESULTS: sTfR decreased in the intervention group (-0.80 mg/L) but increased in the reference group (0.47 mg/L) at 1 year (p=0.0001).Body iron stores (BIS) increased in the intervention group (0.09 mg/kg body weight) and decreased (-0.58 mg/kg body weight) in the reference group at 1 year (p=0.028).These findings indicate an increase in iron deficiency in the reference group and a decrease in the intervention group. However, no changes in serum ferritin and urinary iodine were observed in either group or between groups. CONCLUSIONS: Iron status can be improved in schoolchildren in Tamil Nadu by increasing the amount of micronutrients in the fortified salt used for preparing noon-time school meals.

Pharmaceutical salts/cocrystals of enoxacin with dicarboxylic acids: Enhancing in vitro antibacterial activity of enoxacin by improving the solubility and permeability.

Base on improving the solubility and permeability of enoxacin (EX) to enhance the antibacterial activity in vitro, three new pharmaceutical salts/cocrystals of EX with oxalic acid (EX·0.5(C2H2O4)·2(H2O)), malonic acid ((HEX)·C3H3O4) and fumaric acid ((HEX)·C4H3O4) have been designed, synthesized and characterized. Comprehensive analysis structure and Hirshfeld surface reveal that the hydrogen bonds/CAHBs formed by the N atom in the piperazine ring from EX molecule with the carboxylic acid group in the coformer could form a stable crystal structure. It is universally acknowledged that improving the solubility of the EX (BCS class II) to make it a BCS class I drug would obtain a Bioequivalence of immunity to the drug trial. The solubilities of three pharmaceutical salts/cocrystals of EX with dicarboxylic acids are consistent with expectation that they are dramatically improved in pure water than pure enoxacin, and the solubility order of three pharmaceutical salts/cocrystals of EX is consistent with coformers solubility. The permeabilities of three pharmaceutical salts/cocrystals of EX are improved compared with the pure enoxacin, and the variation tendency is consistent with the solubilities of three pharmaceutical salts/cocrystals of EX. In addition, the antibacterial activities in vitro of three pharmaceutical salts/cocrystals of EX are improved compared with the corresponding parent compound (EX), which change the order is consistent with the solubility and permeability. Simultaneously, the hygroscopic stabilities of three pharmaceutical salts/cocrystals are surpassing pure EX, and the hygroscopic stability of molecular cocrystal EX-OXA is better than ionic cocrystal EX-MLO and EX-FUM. This implies that preparation of the pharmaceutical salts/cocrystals of EX with oxalic acid, malonic acid and fumaric acid could not only enhance the antibacterial activity of EX, which base on improving the solubility and permeability of EX, but also improve the hygroscopic stability of EX.

Inhalations with Brine Solution from the 'Wieliczka' Salt Mine Diminish Airway Hyperreactivity and Inflammation in a Murine Model of Non-Atopic Asthma.

Inhalations with brine solutions are old but underestimated add-ons to pharmacological treatments of inflammatory lung diseases. Although widely used, not all features underlying their action on the respiratory system have been explored. The aim of the present study was to elucidate the mechanism of the beneficial action of inhalations of brine solution from the 'Wieliczka' Salt Mine, a Polish health resort, in a murine model of non-atopic asthma. Asthma was induced in BALB/c mice by skin sensitization with dinitrofluorobenzene followed by an intratracheal challenge of cognate hapten. All animals underwent 12 inhalation sessions with brine solution, pure water or physiological saline. Control mice were not inhaled. We found that brine inhalations reduced, as compared to non-inhaled mice, the typical asthma-related symptoms, like airway hyperreactivity (AHR), the infiltration of pro-inflammatory cells into the bronchial tree, and the inflammation of the airways at the level of pro-inflammatory cytokines IL-1α, IL-1ß and IL-6. The level of the anti-inflammatory IL-10 was elevated in brine-inhaled mice. Inhalations with pure water increased AHR, whereas saline had no influence, either on AHR or cytokine concentrations. These observations indicate that inhalations with a brine solution from the 'Wieliczka' Salt Mine diminish the asthma-related symptoms, mostly by reducing the inflammatory status and by decreasing AHR.

Salt Taste, Nutrition, and Health.

The sodium ion (Na+) is essential for life [...].

Endurance exercise protects aging Drosophila from high-salt diet (HSD)-induced climbing capacity decline and lifespan decrease by enhancing antioxidant capacity.

A high-salt diet (HSD) is a major cause of many chronic and age-related defects such as myocardial hypertrophy, locomotor impairment and mortality. Exercise training can efficiently prevent and treat many chronic and age-related diseases. However, it remains unclear whether endurance exercise can resist HSD-induced impairment of climbing capacity and longevity in aging individuals. In our study, flies were given exercise training and fed a HSD from 1-week old to 5-weeks old. Overexpression or knockdown of salt and dFOXO were built by UAS/Gal4 system. The results showed that a HSD, salt gene overexpression and dFOXO knockdown significantly reduced climbing endurance, climbing index, survival, dFOXO expression and SOD activity level, and increased malondialdehyde level in aging flies. Inversely, in a HSD aging flies, endurance exercise and dFOXO overexpression significantly increased their climbing ability, lifespan and antioxidant capacity, but they did not significantly change the salt gene expression. Overall, current results indicated that a HSD accelerated the age-related decline of climbing capacity and mortality via upregulating salt expression and inhibiting the dFOXO/SOD pathway. Increased dFOXO/SOD pathway activity played a key role in mediating endurance exercise resistance to the low salt tolerance-induced impairment of climbing capacity and longevity in aging DrosophilaThis article has an associated First Person interview with the first author of the paper.

Liquid water intake of the lone star tick, Amblyomma americanum: Implications for tick survival and management.

Ixodid ticks are ectoparasites that feed exclusively on blood as their source of nutrients. Although ticks spend most of their life off the host, until now it has been assumed that the blood and the water vapor are the only sources of water to maintain water balance and prevent desiccation. Here we report for the first time that adult lone star ticks, Amblyomma americanum, also actively drink nutrient-free water, which greatly increases their survival. The volume of ingested water is greater in females than males (0.55 ± 0.06 vs 0.44 ± 0.07 µl) and most likely due to differences in tick size. Water uptake occurs through mouthparts and it can be later observed in the salivary glands and the midgut. We also exploited this behavior by adding a variety of inorganic compounds and microorganisms to water. Addition of inorganic salts to drinking water such as KH2PO4 + NaCl+KNO3 resulted in 100% tick mortality within 3 days. As a proof of concept for using the water drinking as a delivery route of toxic reagents for ticks, we also show that adding Pseudomonas aeruginosa to drinking water quickly leads to tick death. This tick behavior can be exploited to target important physiological systems, which would make ticks vulnerable to dehydration and microbial dysbiosis.

Excess salt intake promotes M1 microglia polarization via a p38/MAPK/AR-dependent pathway after cerebral ischemia in mice.

A high salt diet (HSD) is among the most important risk factors for many diseases. One mechanism by which HSD aggravates cerebral ischemic injury is independent of blood pressure changes. The direct role of HSD in inflammation after cerebral ischemia is unclear. In this research, after twenty-one days of being fed a high salt diet, permanent focal ischemia was induced in mice via operation. At 12 h and 1, 3 and 5 days postischemia, the effects of HSD on the lesion volume, microglia polarization, aldose reductase (AR) expression, and inflammatory processes were analyzed. We report that in mice, surplus dietary salt promotes inflammation and increases the activation of classical lipopolysaccharide (LPS)-induced microglia/macrophages (M1). This effect depends on the expression of the AR protein in activated microglia after permanent middle cerebral artery ligation (pMCAL) in HSD mice. The administration of either the AR inhibitor Epalrestat or a p38-neutralizing antibody blocked the polarization of microglia and alleviated stroke injury. In conclusion, HSD promotes polarization in pro-inflammatory M1 microglia by upregulating the expression of the AR protein via p38/MAPK, thereby exacerbating the development of ischemia stroke.

Comparing the Influence of High Doses of Different Zinc Salts on Oxidative Stress and Energy Depletion in IPEC-J2 Cells.

The current study aimed to investigate the influence of four supplemental zinc salts (chelated: Zn glycine; non-chelated: Zn sulfate, Zn citrate, Zn gluconate) among different zinc concentrations (30-300 µM) on cell proliferation, oxidative stress, and energy depletion in intestinal porcine jejunum epithelial cells (IPEC-J2). Different zinc salts affected cell viability in a time- and dose-dependent manner, which was mainly dependent on the uptake of intracellular Zn2+. Intracellular Zn2+ of Zn sulfate has taken up almost twice as high as Zn glycine when cells were loaded with 100-200 µM zinc. After loading cells with 300 µM zinc, Zn glycine and Zn sulfate had a similar trend in accumulation of Zn2+. When the intracellular Zn2+ overloads, cells will gradually be damaged and subsequently die bearing biochemical features of necrosis or late apoptosis. Meanwhile, obviously, increased levels of intracellular ROS, mitochondrial ROS, MDA, and NO and decreased levels of GSH were observed. Excessive intracellular Zn2+ significantly decreased mitochondria membrane potential accompanied by an obvious loss of ATP and NAD+ levels. Overall, exposure to high doses of zinc salts caused cell damage, which was mainly dependent on the uptake of Zn2+. Zinc overload induced oxidative stress and energy depletion in IPEC-J2 cells, and the cell damage with non-chelated zinc addition was more serious than Zn glycine.

Five-Day Changes in Biomarkers of Exposure Among Adult Smokers After Completely Switching From Combustible Cigarettes to a Nicotine-Salt Pod System.

INTRODUCTION: This study examined changes in biomarkers of exposure (BoE) after 5 days of nicotine-salt pod system (NSPS) use, compared with continuation of usual-cigarette smoking and cigarette abstinence, among adult combustible cigarette smokers. AIMS AND METHODS: A randomized, open-label, parallel-cohort, confinement study of healthy adult smokers, naive to NSPS use, was conducted. Participants (N = 90) were randomized to six cohorts (n = 15 each): exclusive ad libitum use of NSPS (four flavors: Virginia Tobacco, Mint, Mango, Creme), continuation of usual-brand cigarette smoking, or cigarette abstinence. Total nicotine equivalents and BoE (NNN, NNAL, 3-HPMA, MHBMA, S-PMA, HMPMA, CEMA, 1-OHP, and COHb) were measured. RESULTS: Eight non-nicotine BoEs, measured in urine, were reduced by an aggregate of 85.0% in the pooled NSPS cohort; increased by 14.4% in the cigarette cohort (p < .001 for pooled NSPS vs. cigarette); and reduced by 85.3% in the abstinence cohort (p > .05; 99.6% relative reduction between pooled NSPS vs. abstinence). Similar changes in individual BoEs were also observed (p < .001 for each BoE between pooled NSPS vs. cigarettes; and abstinence vs. pooled NSPS; p > .05 for each BoE between pooled NSPS vs. abstinence). Blood COHb decreased by 71.8% in the pooled NSPS cohort and 69.1% in the abstinence cohort (p > .05) and increased by 13.3% in the cigarette cohort (p < .001). Mean total urine nicotine equivalents increased in the pooled NSPS and cigarette cohorts by 9% and 26%, respectively, and did not significantly differ (p > .05). CONCLUSION: Complete switching from cigarettes to NSPS produced significant reductions in key non-nicotine BoEs associated with cigarette smoking. IMPLICATIONS: The results of this study concorded with evidence that complete switching from combustible cigarettes to tobacco and nontobacco-flavored vapor products may reduce exposure to key carcinogens and other toxicants known to be associated with tobacco-related diseases. Future research is needed to assess the long-term health effects of NSPS use. These results should not be interpreted to mean that the use of NSPS is without any risk, particularly for nonusers of tobacco products.

Intake of myo-inositol hexaphosphate and urinary excretion of inositol phosphates in Wistar rats: Gavage vs. oral administration with sugar.

OBJECTIVE: To evaluate the urinary levels of inositol phosphates (InsPs) in rats that received different salts of myo-inositol hexaphosphate (InsP6) by gavage or by oral administration. METHODS: Thirty rats received AIN-76A diet (in which InsPs are undetectable) for 15 days. Then, 12 rats received InsP6 by gavage as a Na salt or a Ca/Mg salt; after 4 days, the Na or Ca/Mg InsP6 was administered with water containing 15 g/L sucrose and urine samples were collected. The other 18 rats received oral InsP6, in which 0.5 g of sugar was combined with InsP6 as a Na salt, a Ca/Mg salt, or a Na salt with CaCO3; daily urine samples were collected. Urine levels of InsPs were determined using a nonspecific method and a specific method (polyacrylamide gel electrophoresis, PAGE), and different InsPs were identified by mass spectroscopy (MS). RESULTS: After 15 days of the InsP6-free diet, the non-specific method detected no urinary InsPs, and MS detected only InsP2. After administration of Na-InsP6 by gavage, the non-specific method indicated more urinary InsPs than the amount of InsP6 determined by PAGE. MS indicated the presence of urinary InsP2, InsP3, InsP4, InsP5, and InsP6 in these rats, with notable variations among animals. Use of the same treatment to administer Ca/Mg-InsP6 led to a lower overall content of urinary InsPs and a lower level of InsP6. Oral administration of InsP6 as a sugar pill led to lower urinary levels of InsPs than administration of InsP6 by gavage, and administration as a Ca/Mg pill or a Ca/Mg pill with CaCO3 led to lower levels than administration as a Na pill. CONCLUSION: Administration of InsP6 to rats leads to the excretion of a mixture of different InsPs. Rats more effectively absorb InsP6 when supplied without dietary components that interfere with its uptake, such as the Ca ion and sugar.

Comparative study of the bioavailability of magnesium salts.

Background High values of endogenous levels of magnesium (Mg) in the body and mechanisms of homeostasis regulation make it difficult to assess the bioavailability of these drugs. The aim of this study was to assess the Mg concentration in blood in volunteers and in erythrocytes in patients with hypomagnesemia. Methods The study included 20 healthy volunteers and 62 patients with chronic heart failure (CHF) I-III functional class (FC) NYHA classification. We studied the composition of Mgorotate and Mgorotate plus potassium (К)orotate. Blood sampling was carried out at 8 a.m. and within 10 h after administering the drugs. Measurement of Mg pharmacokinetic parameters: AUC (concentration of the active substance-time), and Cmax (maximum concentration) in volunteers and measurement of the concentration of Mg in erythrocytes of patients. Results The results indicated that both the AUC in volunteers and concentration of Mg in erythrocytes of patients are comparable, and the differences are not statistically significant. Conclusions The study showed that the standard method of calculating the AUC (total serum Mg) is insufficient for comparative evaluation of Mg absorption due to the high levels of its endogenous content and a small increase in concentration after taking the drugs. It is advisable to assess the concentration of Mg in the red blood cells of patients.

The Possibilities of Using Chromium Salts as an Agent Supporting Treatment of Polycystic Ovary Syndrome.

The polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women in reproductive age with the so far undetermined causes of development. In the etiopathogenesis of PCOS, the role of insulin resistance is emphasised, which was an indication for the attempts at using chromium III salts (Cr) in augmenting pharmacotherapy applied in patients. The analysis of the usefulness and efficacy of this approach was the direct goal of this thesis. Animal tests confirmed the efficacy of chromium in maintaining the appropriate level of glycaemia and insulinaemia, normalisation of plasma concentrations of microelements and also a correlation between the Cr level, insulin and dehydroepiandrosterone (DHEA) was found. A decrease in the expression of 3ß-hydroxysteroid dehydrogenase and 17ß-hydroxysteroid dehydrogenase was identified in adipose tissue. Clinical studies, although sparse, show that the supplementation with chromium can improve BMI and the parameters evaluating the control of glycaemia and increase the chances for ovulation and regular menstruation. However, the small number and a variability in study protocols makes comparing them very difficult. A completely new subject that has not been yet studied is the possibility of using chromium in levelling mood disorders in patients with PCOS. Currently, there are still no sufficient proofs for introducing chromium as a standard in treating and preventing insulin resistance in patients with PCOS. However, this direction remains open, and treating insulin resistance is an important challenge in clinical practice.